데이터 상품 상세검색

[의료]

비임상 데이터셋

비임상 데이터셋

  • 등록일2023-07-06
  • 조회수520
  • 다운로드207
  • 카테고리의료
  • 10

데이터 기본 이용료

  • 1,000,000원
상세정보
데이터등록일 데이터 수정일 데이터 이용기한 판매제공처
2023-07-06 2023-07-06 무기한 비네아
데이터 제공포맷 데이터 제공방식 데이터 파일용량 데이터 상품구분
json/zip 다운로드 61.00 KB dataset

● 데이터 상품명 비임상 데이터셋 ● 데이터 상품 부제 COVID-19의 비임상 관련 신약개발 데이터셋 ● 데이터 상품 요약 인용지수 상위 의학저널에 게재된 COVID-19의 비임상에 관련된 의학 학술논문 데이터 ● 키워드 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 의학논문의 저자 키워드 및 제목과 키워드에서 추출한 키워드에 대하여 키워드 속성, 대역어, 키워드 출처, 논문 DOI, 저자, 발행연월, 논문URL, 저널명, 저널 ISSN, 발행기관, Impact Factor의 정보를 매핑한 데이터 ■ 컬럼(속성) 정보 - 키워드명 : 키워드 - 키워드속성 : 키워드 성격 - 키워드출처 : 키워드 출현 위치 - 키워드대역어 : 자체 보유 의학사전 및 구글번역기에 의한 대역어 - 논문DOI명 : 키워드 출현 논문의 DOI - 논문제목 : 키워드 출현 논문의 제목 - 논문저자 : 키워드 출현 논문의 저자 - 논문발행연월 : 키워드 출현 논문의 발행연월 - 논문초록 : 키워드 출현 논문의 초록 - 논문URL : 키워드 출현 논문의 URL - 저널ISSN명 : 키워드 출현 논문의 저널 ISSN - 저널제목 : 키워드 출현 논문의 저널명 - 저널발행기관명 : 키워드 출현 논문의 발행기관명 ● 연관 데이터셋 상품 정보 ■ 상품 설명 및 특징 - 특정 키워드의 연관 키워드를 co-occurrence 기법과 Latent Semantic Algorithm에 의해 추출한 데이터셋 ■ 컬럼(속성) 정보 - 키워드명 : 키워드 - 키워드속성 : 키워드의 성격 - 연관키워드명 : 키워드와 연관된 키워드 - 연관키워드 속성 : 연관키워드의 속성 - 연관중요도 : 동의여 여부와 동시출현수를 지표로 하는 중요도 ● 기간 및 범위 - 2014년 5월 ~ 2022년 12월 ● 활용 예제 - 특정 주제에 해당되는 키워드의 속성별, 저널별, 연도별, 저자별 추이 - 키워드의 연관어를 속성별, 저널별, 연도별, 저자별 분석

샘플정보
ID
카테고리ID
카테고리명
키워드명
키워드속성
대체키워드명
키워드출처
키워드대역어
논문ID
논문DOI명
논문제목
논문저자
논문발행연월
논문유형
논문출처
논문초록
논문URL
저널ID
저널ISSN명
저널제목
저널발행기관명
저널ImpactFactor명
4460 5001 비임상 Study protocol Term study protocol abstract 연구 프로토콜 2621 10.1186/s12890-021-01619-y Randomized, placebo controlled, double blinded pilot superiority phase 2 trial to evaluate the effect of curcumin in moderate to severe asthmatics Michele Quan@@@Abdullah Alismail@@@Noha Daher@@@Derrick Cleland@@@Sonia Chavan@@@Laren D. Tan 202108 Study Protocol PMC Background Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment. Methods This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500?mg or matching placebo by mouth twice daily for the study period of 12?weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time. Discussion The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin’s role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19. Trial registration This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369320/ 442 1471-2466 BMC Pulmonary Medicine London : BioMed Central
19553 5001 비임상 Evidence Term evidence abstract None 35722 10.1016/j.cjca.2020.04.010 Management and Treatment of COVID-19: The Chinese Experience Fujun Peng MD@@@Lei Tu MD@@@ PhD@@@Yongshi Yang MD@@@Peng Hu MD@@@Runsheng Wang MD@@@Qinyong Hu MD@@@Feng Cao MD@@@Taijiao Jiang PhD@@@Jinlyu Sun MD@@@Guogang Xu MD@@@ PhD@@@Christopher Chang MD@@@ PhD 202006 Review article Sciencedirect Abstract!!With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of “Fangcang” shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls. https://doi.org/10.1016/j.cjca.2020.04.010 1569 0828-282X The Canadian journal of cardiology Oxford, UK : Elsevier.
19550 5001 비임상 Delay Term delay abstract 지체하다 35722 10.1016/j.cjca.2020.04.010 Management and Treatment of COVID-19: The Chinese Experience Fujun Peng MD@@@Lei Tu MD@@@ PhD@@@Yongshi Yang MD@@@Peng Hu MD@@@Runsheng Wang MD@@@Qinyong Hu MD@@@Feng Cao MD@@@Taijiao Jiang PhD@@@Jinlyu Sun MD@@@Guogang Xu MD@@@ PhD@@@Christopher Chang MD@@@ PhD 202006 Review article Sciencedirect Abstract!!With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of “Fangcang” shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls. https://doi.org/10.1016/j.cjca.2020.04.010 1569 0828-282X The Canadian journal of cardiology Oxford, UK : Elsevier.
5060 5001 비임상 Immune cell Cell immune cell abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
19559 5001 비임상 Hydroxychloroquine Drug hydroxychloroquine abstract 하이드록시클로로퀸 35722 10.1016/j.cjca.2020.04.010 Management and Treatment of COVID-19: The Chinese Experience Fujun Peng MD@@@Lei Tu MD@@@ PhD@@@Yongshi Yang MD@@@Peng Hu MD@@@Runsheng Wang MD@@@Qinyong Hu MD@@@Feng Cao MD@@@Taijiao Jiang PhD@@@Jinlyu Sun MD@@@Guogang Xu MD@@@ PhD@@@Christopher Chang MD@@@ PhD 202006 Review article Sciencedirect Abstract!!With more than 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. This paper provides a critical review of the available evidence regarding the lessons learned from the Chinese experience with COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits, which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hubei Province and the rest of the country, as well as closure of all schools and nonessential businesses. Other measures included the rapid construction of two new hospitals and the establishment of “Fangcang” shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high-flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin, and convalescent plasma infusions. These measures appeared to provide only moderate success. Although some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers, and contacts and early implementation of quarantine measures with an organised, proactive, and unified strategy at a national level. Delays result in significantly higher death tolls. https://doi.org/10.1016/j.cjca.2020.04.010 1569 0828-282X The Canadian journal of cardiology Oxford, UK : Elsevier.
5061 5001 비임상 immune cells Cell immune cell abstract 면역 세포 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5076 5001 비임상 Mitigation Term mitigation title 완화 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4970 5001 비임상 randomized placebo-controlled trial Term randomized placebo-controlled trial abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4971 5001 비임상 Randomly Term randomly abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4972 5001 비임상 RANK Term RANK abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4973 5001 비임상 RCT Term rct abstract RCT 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4974 5001 비임상 recruited Action recruited abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4975 5001 비임상 reduce Action reduce abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4314 5001 비임상 low dose Term low dose abstract 저선량 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4315 5001 비임상 LPS Compound lp abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4976 5001 비임상 Registered Action registered abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4316 5001 비임상 lung Organ lung abstract 허파 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4977 5001 비임상 registration number Term registration number abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4978 5001 비임상 registry Term registry abstract 등록체계 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4979 5001 비임상 Result Term result abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4980 5001 비임상 Safe Term safe abstract 금고 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4981 5001 비임상 shown Action shown abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4982 5001 비임상 Side effect Term side effect abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4983 5001 비임상 significance level Term significance level abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4985 5001 비임상 Signs and symptoms Term signs and symptom abstract 징후와 증상 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4317 5001 비임상 Lung injury Disease lung injury abstract 폐 손상 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4081 5001 비임상 appear Action appear abstract None 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4986 5001 비임상 supplementary material Term supplementary material abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4987 5001 비임상 sustained Action sustained abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4988 5001 비임상 Symptom Symptom symptom abstract 증상 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
21687 5001 비임상 team Term team title None 35788 10.1016/j.otc.2021.12.013 Developing an Integrated Multidisciplinary Pituitary Management Team Erin L. McKean MD@@@ MBA@@@Stephen E. Sullivan MD 202204 Review article Sciencedirect https://doi.org/10.1016/j.otc.2021.12.013 2764 0030-6665 Otolaryngologic Clinics of North America Philadelphia Pa : W B Saunders.
4989 5001 비임상 threshold Term threshold abstract 문턱값 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4990 5001 비임상 Treatment Treatment treatment abstract 치료 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4991 5001 비임상 Treatment effectiveness Term treatment effectiveness abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4992 5001 비임상 treatment period Term treatment period abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4993 5001 비임상 was used Action was used abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4318 5001 비임상 lung tissue Organ lung tissue abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4994 5001 비임상 were assessed Action were assessed abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4319 5001 비임상 lung tissues Organ lung tissue abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
22568 5001 비임상 recent Term recent title abnormality 35821 10.1016/j.cimid.2021.101615 Recent advances in non-specific immune memory against bovine tuberculosis F.C. Blanco@@@J. Sabio y Garcia@@@F. Bigi 202104 Review article Sciencedirect Abstract!!Bovine tuberculosis is an important worldwide disease mainly related to cattle, although it also affects other mammals, including humans. In recent years, there have been considerable advances in the knowledge of the immune response mechanisms underlying the interaction of Mycobacterium bovis, the main agent of bovine tuberculosis, with its hosts. In this review we describe the most recent findings on the cattle immune response to M. bovis, particularly regarding trained innate immune responses and γδ T cells, that could support the development of vaccines and diagnostic tools to control this disease. https://doi.org/10.1016/j.cimid.2021.101615 2772 0147-9571 Comparative Immunology, Microbiology and Infectious Diseases Exeter : Elsevier Science Ltd.
4995 5001 비임상 Wilcoxon Signed Ranks test Term wilcoxon signed ranks test abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4354 5001 비임상 western blotting Term western blotting abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
5090 5001 비임상 property Term property title None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5091 5001 비임상 Protein Protein protein abstract 단백질 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5092 5001 비임상 Proteins Protein protein abstract 단백질 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5093 5001 비임상 Protein target Term protein target abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4095 5001 비임상 High-dose Term high-dose abstract None 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4891 5001 비임상 COVID-19 Disease covid-19 author 코로나-19 5555 10.21010/ajidv15i2S.3 GENERATING RESPONSES IMMUNE IN CELLULAR AND HUMORAL TREATMENT WITH EPITOPE SPIKE, EPITOPE ENVELOPE PROTEIN, AND EPITOPE MEMBRANE PROTEIN SARS-COV-2, HONEY, SAUSSUREA LAPPA , AND NIGELLA SATIVA Sumarno Reto Prawiro@@@Meike Tiya Kusuma@@@Reyhan Amiruddin@@@Irma Nur Sukmawati@@@Yuyun Kusnaningrum@@@Jayshri Davi S Nadarajah@@@Khoirul Anam@@@Tri Yudani Mardining Raras@@@Sri Winarsih 202109 Article PMC Abstract Background: Covid-19 has become pandemic in the World, including Indonesia. Our last study showed that HSF could serve as an immunomodulator. Using the exact search, we found that the most immuno-dominant SARS-COV2 epitope, namely A spike protein epitope, B envelope protein epitope, and C membrane protein epitope, we concise to be HF Materials and Methods: We used to post only control design study and mice as an animal model. The research divided mice into four groups, and the first group as control received PBS as a placebo. The second, three, and last four groups gave HF, HSN, and HFHSN (combine HF and HSN). All of the regiment enters the mouth with a special sonde to reach the gastrointestinal organ. We gave HF every week three times and HSN once a day. After administration regiments for a long three weeks, we sacrificed the mice. We evaluated cellular immune responses that are Th-2, Th-17, and NK cells. We check for humoral immune response, TGF-β,IL-17A, IL-4, IgG,IL-4, β-defensin, and s-IgA. Results: Highest profile cellular immunity HF, HSN, and HFHSN were NK cell, Th-2 and Th-17, and the last NK cell, respectively. After that which in humoral immunity, the domination response IgG and IL-4 were HF. But HSN and HFHSN dominated for s-IgA and β-defensin production. By using the study Bio-Informatica, we found HF. Conclusion: If the results of this study are continued to the clinical trial level, it is necessary to recommend additional markers such as CTL (s-IgA and β-defensin in lung tissue)and CPE assay. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457347/ 522 2006-0165 African Journal of Infectious Diseases
4104 5001 비임상 I-P-R-F Protein I-P-R-F abstract None 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4105 5001 비임상 I-R-F Protein I-R-F abstract None 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4342 5001 비임상 Support Term support abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4343 5001 비임상 survival rate Term survival rate abstract 생존율 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
5062 5001 비임상 Immunosuppression Treatment immunosuppression abstract 면역억제 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4996 5001 비임상 2019 coronavirus disease Term 2019 coronavirus disease abstract 2019 코로나 바이러스 질병 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
23286 5001 비임상 content Term content title None 35841 10.1016/S0002-9378(20)30914-5 Table of Contents 202009 Article Sciencedirect https://doi.org/10.1016/S0002-9378(20)30914-5 355 0002-9378 American journal of obstetrics and gynecology New York : Elsevier.
4344 5001 비임상 TCM Term tcm abstract None 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4997 5001 비임상 ACE2 Enzyme ace2 abstract 안지오텐신 전환효소 2 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4998 5001 비임상 activity Term activity abstract 활성 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4999 5001 비임상 Affect Term affect abstract abnormality 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5000 5001 비임상 agent Term agent title None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4082 5001 비임상 Biological techniques Term biological technique author 생물학적 기술 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4083 5001 비임상 breath Term breath author 호흡 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
5001 5001 비임상 Alter Term alter abstract abnormality 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4345 5001 비임상 therapy Treatment therapy abstract 치료 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4346 5001 비임상 tight junction Term tight junction abstract 치밀이음 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
23844 5001 비임상 PDF Gene PDF title None 35855 10.1016/S2666-0873(20)30139-3 Full Issue PDF 202006 Article Sciencedirect https://doi.org/10.1016/S2666-0873(20)30139-3 2778 2666-0873 JACC: CardioOncology New York: Elsevier Inc.
5002 5001 비임상 analyse Term analyse abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
23955 5001 비임상 expression Action expression abstract 표현 35862 10.1016/j.pharmthera.2020.107676 A novel rationale for targeting FXI: Insights from the hemostatic microRNA targetome for emerging anticoagulant strategies Jamie Nourse@@@Sven Danckwardt 202102 Review article Sciencedirect Abstract!!Therapeutic targeting of blood coagulation is a challenging task as it interferes with the delicate balance of pro- and anticoagulant activities. Anticoagulants are employed in millions of thrombophilic patients worldwide each year. The treatment and prevention of venous thromboembolism has changed drastically. Traditional vitamin K antagonists are being replaced by direct oral anticoagulants (DOACs), which selectively target coagulation factors Xa or IIa. However for a growing population with comorbidities satisfying therapeutic options are still lacking and the quest for novel therapeutics continues. Recently, targeting factors XI or XII have emerged as new therapeutic strategies. As these factors play important roles in thrombosis, yet are essentially dispensable for hemostasis, these strategies may overcome the obstacle of treating or preventing thrombosis without affecting hemostasis. Based on the recent elucidation of the hemostatic microRNA targetome, we introduce and discuss a hitherto unrecognized rationale for the therapeutic targeting of factor XI. This is based on mimicking endogenous factor XI expression control by therapeutic delivery of microRNA mimics. We discuss the functional difference between various gene-targeting approaches, and propose the hemostatic system to represent an ideal model for assessment of the efficacy and safety of such therapeutic components, ushering in a novel therapeutic era with broad applicability. https://doi.org/10.1016/j.pharmthera.2020.107676 1631 0163-7258 Pharmacology & therapeutics Oxford, Elmsford, N. Y., Pergamon Press.
23954 5001 비임상 Efficacy and safety Term efficacy and safety abstract 효능과 안전성 35862 10.1016/j.pharmthera.2020.107676 A novel rationale for targeting FXI: Insights from the hemostatic microRNA targetome for emerging anticoagulant strategies Jamie Nourse@@@Sven Danckwardt 202102 Review article Sciencedirect Abstract!!Therapeutic targeting of blood coagulation is a challenging task as it interferes with the delicate balance of pro- and anticoagulant activities. Anticoagulants are employed in millions of thrombophilic patients worldwide each year. The treatment and prevention of venous thromboembolism has changed drastically. Traditional vitamin K antagonists are being replaced by direct oral anticoagulants (DOACs), which selectively target coagulation factors Xa or IIa. However for a growing population with comorbidities satisfying therapeutic options are still lacking and the quest for novel therapeutics continues. Recently, targeting factors XI or XII have emerged as new therapeutic strategies. As these factors play important roles in thrombosis, yet are essentially dispensable for hemostasis, these strategies may overcome the obstacle of treating or preventing thrombosis without affecting hemostasis. Based on the recent elucidation of the hemostatic microRNA targetome, we introduce and discuss a hitherto unrecognized rationale for the therapeutic targeting of factor XI. This is based on mimicking endogenous factor XI expression control by therapeutic delivery of microRNA mimics. We discuss the functional difference between various gene-targeting approaches, and propose the hemostatic system to represent an ideal model for assessment of the efficacy and safety of such therapeutic components, ushering in a novel therapeutic era with broad applicability. https://doi.org/10.1016/j.pharmthera.2020.107676 1631 0163-7258 Pharmacology & therapeutics Oxford, Elmsford, N. Y., Pergamon Press.
24096 5001 비임상 Mouse double minute 2 homolog Term mouse double minute 2 homolog author None 35867 10.1016/j.arr.2020.101251 Senescent cells as promising targets to tackle age-related diseases Eva Pra?nikar@@@Jure Bori?ek@@@Andrej Perdih 202103 Review article Sciencedirect Abstract!!As the world's population progressively ages, the burden on the socio-economic and health systems is escalating, demanding sustainable and lasting solutions. Cellular senescence, one of the hallmarks of ageing, is a state of irreversible cell cycle arrest that occurs in response to various genotoxic stressors and is considered an important factor in the development of many age-related diseases and therefore a potential therapeutic target. Here, the role of senescent cells in age-related diseases is discussed, focusing on their formation and main characteristics. The mechanisms leading to senescent cells are presented, including replicative and premature senescence as well as senescence that occurs in various physiological processes, such as wound healing. The second part comprises a comprehensive description of various biomarkers currently used for the detection of senescent cells along with the investigated therapeutic approaches, namely senolytics, senomorphics and the clearance of senescent cells by the immune system. Potential delivery systems suitable for such therapies and model organisms to study senescence are also briefly examined. This in-depth overview of cellular senescence contributes to a deeper understanding of a rapidly evolving area aimed to tackle the age-related diseases in a more mechanistic way, as well as highlights future research opportunities. https://doi.org/10.1016/j.arr.2020.101251 1699 1568-1637 Ageing research reviews Oxford, UK : Elsevier Science
24095 5001 비임상 MK2Mitogen-activated protein kinase-activated protein kinase 2 Term mk2mitogen-activated protein kinase-activated protein kinase 2 author None 35867 10.1016/j.arr.2020.101251 Senescent cells as promising targets to tackle age-related diseases Eva Pra?nikar@@@Jure Bori?ek@@@Andrej Perdih 202103 Review article Sciencedirect Abstract!!As the world's population progressively ages, the burden on the socio-economic and health systems is escalating, demanding sustainable and lasting solutions. Cellular senescence, one of the hallmarks of ageing, is a state of irreversible cell cycle arrest that occurs in response to various genotoxic stressors and is considered an important factor in the development of many age-related diseases and therefore a potential therapeutic target. Here, the role of senescent cells in age-related diseases is discussed, focusing on their formation and main characteristics. The mechanisms leading to senescent cells are presented, including replicative and premature senescence as well as senescence that occurs in various physiological processes, such as wound healing. The second part comprises a comprehensive description of various biomarkers currently used for the detection of senescent cells along with the investigated therapeutic approaches, namely senolytics, senomorphics and the clearance of senescent cells by the immune system. Potential delivery systems suitable for such therapies and model organisms to study senescence are also briefly examined. This in-depth overview of cellular senescence contributes to a deeper understanding of a rapidly evolving area aimed to tackle the age-related diseases in a more mechanistic way, as well as highlights future research opportunities. https://doi.org/10.1016/j.arr.2020.101251 1699 1568-1637 Ageing research reviews Oxford, UK : Elsevier Science
5055 5001 비임상 human gene Gene human gene abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5056 5001 비임상 human genes Gene human gene abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5057 5001 비임상 hypothetical Term hypothetical abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5058 5001 비임상 identify Action identify abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
5059 5001 비임상 Immediate Term immediate abstract None 5757 10.3390/biomedicines8050129 Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells Gennadi V. Glinsky 202005 Article PMC Genes required for SARS-CoV-2 entry into human cells, ACE2 and FURIN, were employed as baits to build genomic-guided molecular maps of upstream regulatory elements, their expression and functions in the human body, and pathophysiologically relevant cell types. Repressors and activators of the ACE2 and FURIN genes were identified based on the analyses of gene silencing and overexpression experiments as well as relevant transgenic mouse models. Panels of repressors ( VDR; GATA5; SFTPC; HIF1a ) and activators ( HMGA2; INSIG1; RUNX1; HNF4a; JNK1/c-FOS ) were then employed to identify existing drugs manifesting in their effects on gene expression signatures of potential coronavirus infection mitigation agents. Using this strategy, vitamin D and quercetin have been identified as putative 2019 coronavirus disease (COVID-19) mitigation agents. Quercetin has been identified as one of top-scoring candidate therapeutics in the supercomputer SUMMIT drug-docking screen and Gene Set Enrichment Analyses (GSEA) of expression profiling experiments (EPEs), indicating that highly structurally similar quercetin, luteolin, and eriodictyol could serve as scaffolds for the development of efficient inhibitors of SARS-CoV-2 infection. In agreement with this notion, quercetin alters the expression of 98 of 332 (30%) of human genes encoding protein targets of SARS-CoV-2, thus potentially interfering with functions of 23 of 27 (85%) of the SARS-CoV-2 viral proteins in human cells. Similarly, Vitamin D may interfere with functions of 19 of 27 (70%) of the SARS-CoV-2 proteins by altering expression of 84 of 332 (25%) of human genes encoding protein targets of SARS-CoV-2. Considering the potential effects of both quercetin and vitamin D, the inference could be made that functions of 25 of 27 (93%) of SARS-CoV-2 proteins in human cells may be altered. GSEA and EPEs identify multiple drugs, smoking, and many disease conditions that appear to act as putative coronavirus infection-promoting agents. Discordant patterns of testosterone versus estradiol impacts on SARS-CoV-2 targets suggest a plausible molecular explanation of the apparently higher male mortality during the coronavirus pandemic. Estradiol, in contrast with testosterone, affects the expression of the majority of human genes (203 of 332; 61%) encoding SARS-CoV-2 targets, thus potentially interfering with functions of 26 of 27 SARS-CoV-2 viral proteins. A hypothetical tripartite combination consisting of quercetin/vitamin D/estradiol may affect expression of 244 of 332 (73%) human genes encoding SARS-CoV-2 targets. Of major concern is the ACE2 and FURIN expression in many human cells and tissues, including immune cells, suggesting that SARS-CoV-2 may infect a broad range of cellular targets in the human body. Infection of immune cells may cause immunosuppression, long-term persistence of the virus, and spread of the virus to secondary targets. Present analyses and numerous observational studies indicate that age-associated vitamin D deficiency may contribute to the high mortality of older adults and the elderly. Immediate availability for targeted experimental and clinical interrogations of potential COVID-19 pandemic mitigation agents, namely vitamin D and quercetin, as well as of the highly selective (Ki, 600 pm) intrinsically specific FURIN inhibitor (a1-antitrypsin Portland (a1-PDX), is considered an encouraging factor. Observations reported in this contribution are intended to facilitate follow-up targeted experimental studies and, if warranted, randomized clinical trials to identify and validate therapeutically viable interventions to combat the COVID-19 pandemic. Specifically, gene expression profiles of vitamin D and quercetin activities and their established safety records as over-the-counter medicinal substances strongly argue that they may represent viable candidates for further considerations of their potential utility as COVID-19 pandemic mitigation agents. In line with the results of present analyses, a randomized interventional clinical trial evaluating effects of estradiol on severity of the coronavirus infection in COVID19+ and presumptive COVID19+ patients and two interventional randomized clinical trials evaluating effects of vitamin D on prevention and treatment of COVID-19 were listed on the ClinicalTrials.gov website. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277789/ 543 2227-9059 Biomedicines Basel: MDPI AG, 2013-
4347 5001 비임상 TNF-α Protein tnf-α abstract 종양괴사인자 알파 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4892 5001 비임상 CPE Gene cpe abstract None 5555 10.21010/ajidv15i2S.3 GENERATING RESPONSES IMMUNE IN CELLULAR AND HUMORAL TREATMENT WITH EPITOPE SPIKE, EPITOPE ENVELOPE PROTEIN, AND EPITOPE MEMBRANE PROTEIN SARS-COV-2, HONEY, SAUSSUREA LAPPA , AND NIGELLA SATIVA Sumarno Reto Prawiro@@@Meike Tiya Kusuma@@@Reyhan Amiruddin@@@Irma Nur Sukmawati@@@Yuyun Kusnaningrum@@@Jayshri Davi S Nadarajah@@@Khoirul Anam@@@Tri Yudani Mardining Raras@@@Sri Winarsih 202109 Article PMC Abstract Background: Covid-19 has become pandemic in the World, including Indonesia. Our last study showed that HSF could serve as an immunomodulator. Using the exact search, we found that the most immuno-dominant SARS-COV2 epitope, namely A spike protein epitope, B envelope protein epitope, and C membrane protein epitope, we concise to be HF Materials and Methods: We used to post only control design study and mice as an animal model. The research divided mice into four groups, and the first group as control received PBS as a placebo. The second, three, and last four groups gave HF, HSN, and HFHSN (combine HF and HSN). All of the regiment enters the mouth with a special sonde to reach the gastrointestinal organ. We gave HF every week three times and HSN once a day. After administration regiments for a long three weeks, we sacrificed the mice. We evaluated cellular immune responses that are Th-2, Th-17, and NK cells. We check for humoral immune response, TGF-β,IL-17A, IL-4, IgG,IL-4, β-defensin, and s-IgA. Results: Highest profile cellular immunity HF, HSN, and HFHSN were NK cell, Th-2 and Th-17, and the last NK cell, respectively. After that which in humoral immunity, the domination response IgG and IL-4 were HF. But HSN and HFHSN dominated for s-IgA and β-defensin production. By using the study Bio-Informatica, we found HF. Conclusion: If the results of this study are continued to the clinical trial level, it is necessary to recommend additional markers such as CTL (s-IgA and β-defensin in lung tissue)and CPE assay. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457347/ 522 2006-0165 African Journal of Infectious Diseases
25443 5001 비임상 significant effect Action significant effect abstract None 78883 10.1371/journal.pone.0277183 Cross-cultural comparison of nudging effects for environmental protection: A case-study of risk-averse attitudes toward disposable plastics Hidenori Komatsu@@@Hiromi Kubota@@@Nobuyuki Tanaka@@@Mariah Griffin@@@Jennifer Link@@@Glenn Geher@@@Maryanne L Fisher 202211 Article PMC {{{ Abstract }}} !! Disposable plastics are drawing considerable attention as a source of environmental risk despite their benefits in daily life. Banning the use of disposable plastics could increase other types of risks, which may damage the public good in the long run. Considering the trade-off of the risks and benefits, one way to improve social welfare is to conduct proper recycling and to continue using plastics but limit them to essential use, avoiding an unnecessary ban. A potential barrier to such a policy might be risk-averse attitudes toward actions that are perceived to threaten future generations, which is a well-known phenomenon. We previously designed a framework for information provision using messages that remind individuals about familial support, which had significant effects in multiple countries on increasing positive attitudes toward air pollution caused by industrialization. We hypothesized that this information provision could also be effective for disposable plastic use. Thus, we conducted a randomized controlled trial via online surveys in Japan, Canada, and the US to identify the effects of our designed messages about recycling on increasing positive attitudes toward disposable plastics. The intervention effects were measured by the difference-in-difference method and panel analysis based on linear regression models using the respondents' attributes and personality traits. The effects were consistently correlated with a sense of familial support, with the effect sizes varying according to country (US &gt; Japan &gt; Canada). Attributes that positively contributed to the message being more effective were higher agreeableness, lower Machiavellianism, lower psychopathy, and being a woman. Although personal fear about COVID-19 moderated the message effects, concern about the threats to relatives and family boosted the effects. Although the effect sizes were influenced by external factors, the results suggested that our proposed framework for information provision has the potential to be applied to a wider variety of risk-related topics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632847/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
25467 5001 비임상 COVID-19 Disease covid-19 title 코로나-19 78884 10.1186/s12967-022-03660-9 Efficacy and safety of Treamid in the rehabilitation of patients after COVID-19 pneumonia: a phase 2, randomized, double-blind, placebo-controlled trial Evgeny Bazdyrev@@@Maria Panova@@@Maria Brachs@@@Elena Smolyarchuk@@@Daria Tsygankova@@@Liudmila Gofman@@@Yana Abdyusheva@@@Fedor Novikov 202211 Article PMC {{{ Abstract }}} !!{{ Background: }} Many patients who recovered from COVID are still suffering from pulmonary dysfunction that can be persistent even for months after infection. Therefore, treatment to prevent irreversible impairment of lung function is needed. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory and antifibrotic effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae. !!{{ Methods: }} The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history (with the first symptoms of COVID appear no earlier than 2 months before screening) and having fibrotic changes in the lungs, decreased lung function (percentage of predicted FVC and/or DLCO &lt; 80%), and moderate or severe dyspnea according to mMRC scale were enrolled and randomly assigned in a 1:1 ratio (stratified by the initial degree of lung damage, age, and concomitant chronic diseases) by use of interactive responsive technology to peroral administration of Treamid 50 mg or placebo once a day for 4 weeks. The primary outcome was the proportion of patients who achieved clinically significant improvement in FVC and/or DLCO (defined as a relative increase in FVC of ≥ 10% or a relative increase in FVC in the range of ≥ 5 to &lt; 10% plus a relative increase in DLCO of ≥ 15%) at week 4 compared with baseline. Secondary endpoints included changes from baseline in dyspnea scoring evaluated by the modified Borg and mMRC scales, pulmonary function (FEV 1 , FVC, FEV 1 /FVC ratio, DLCO, TLC, FRC), 6-min walk distance, the overall score of the KBILD questionnaire, and the proportion of patients with a reduction in the degree of lung damage assessed by CT scores. This trial was registered on ClinicalTrials.gov (Identifier: NCT04527354 ). The study was fully funded by PHARMENTERPRISES LLC. !!{{ Results: }} 12 out of 29 patients (41%) in Treamid group achieved clinically significant improvement in FVC and/or DLCO compared to 5 out of 30 patients (17%) in placebo group (p = 0.036). There was a significant decrease of dyspnea according to modified Borg scale observed in the Treamid group (- 0.9 ± 0.7 vs. - 0.4 ± 0.8, p = 0.018). No significant differences in the adverse events were noted. Exploratory analysis of the female population indicated superiority of Treamid over placebo by decreasing dyspnea and the extent of lung damage as well as increasing TLC. !!{{ Conclusions: }} 4 weeks oral administration of 50 mg Treamid was associated with clinically significant improvement in the post-COVID patients, evident by an increase in FVC and/or DLCO as well as decreasing dyspnea. Treamid was well tolerated and can be safely administered to patients discharged after COVID. Treamid was more effective in women visible by superior improvement of COVID sequalae after 4 weeks treatment. Considering that female gender is a risk factor associated with the development of post-COVID symptoms, Treamid might offer a pharmacological treatment for long-term sequalae after COVID and supports further investigation in future clinical trials in post-COVID patients. !!{{ Keywords: }} COVID; Lung fibrosis; Lung function; NCT04527354 ; Post-COVID rehabilitation; SARS-CoV-2; Treamid. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632561/ 78 1479-5876 Journal of Translational Medicine [London] : BioMed Central
25440 5001 비임상 positive attitude Term positive attitude abstract None 78883 10.1371/journal.pone.0277183 Cross-cultural comparison of nudging effects for environmental protection: A case-study of risk-averse attitudes toward disposable plastics Hidenori Komatsu@@@Hiromi Kubota@@@Nobuyuki Tanaka@@@Mariah Griffin@@@Jennifer Link@@@Glenn Geher@@@Maryanne L Fisher 202211 Article PMC {{{ Abstract }}} !! Disposable plastics are drawing considerable attention as a source of environmental risk despite their benefits in daily life. Banning the use of disposable plastics could increase other types of risks, which may damage the public good in the long run. Considering the trade-off of the risks and benefits, one way to improve social welfare is to conduct proper recycling and to continue using plastics but limit them to essential use, avoiding an unnecessary ban. A potential barrier to such a policy might be risk-averse attitudes toward actions that are perceived to threaten future generations, which is a well-known phenomenon. We previously designed a framework for information provision using messages that remind individuals about familial support, which had significant effects in multiple countries on increasing positive attitudes toward air pollution caused by industrialization. We hypothesized that this information provision could also be effective for disposable plastic use. Thus, we conducted a randomized controlled trial via online surveys in Japan, Canada, and the US to identify the effects of our designed messages about recycling on increasing positive attitudes toward disposable plastics. The intervention effects were measured by the difference-in-difference method and panel analysis based on linear regression models using the respondents' attributes and personality traits. The effects were consistently correlated with a sense of familial support, with the effect sizes varying according to country (US &gt; Japan &gt; Canada). Attributes that positively contributed to the message being more effective were higher agreeableness, lower Machiavellianism, lower psychopathy, and being a woman. Although personal fear about COVID-19 moderated the message effects, concern about the threats to relatives and family boosted the effects. Although the effect sizes were influenced by external factors, the results suggested that our proposed framework for information provision has the potential to be applied to a wider variety of risk-related topics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632847/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
25441 5001 비임상 Randomized controlled trial Term randomized controlled trial abstract 무작위대조시험 78883 10.1371/journal.pone.0277183 Cross-cultural comparison of nudging effects for environmental protection: A case-study of risk-averse attitudes toward disposable plastics Hidenori Komatsu@@@Hiromi Kubota@@@Nobuyuki Tanaka@@@Mariah Griffin@@@Jennifer Link@@@Glenn Geher@@@Maryanne L Fisher 202211 Article PMC {{{ Abstract }}} !! Disposable plastics are drawing considerable attention as a source of environmental risk despite their benefits in daily life. Banning the use of disposable plastics could increase other types of risks, which may damage the public good in the long run. Considering the trade-off of the risks and benefits, one way to improve social welfare is to conduct proper recycling and to continue using plastics but limit them to essential use, avoiding an unnecessary ban. A potential barrier to such a policy might be risk-averse attitudes toward actions that are perceived to threaten future generations, which is a well-known phenomenon. We previously designed a framework for information provision using messages that remind individuals about familial support, which had significant effects in multiple countries on increasing positive attitudes toward air pollution caused by industrialization. We hypothesized that this information provision could also be effective for disposable plastic use. Thus, we conducted a randomized controlled trial via online surveys in Japan, Canada, and the US to identify the effects of our designed messages about recycling on increasing positive attitudes toward disposable plastics. The intervention effects were measured by the difference-in-difference method and panel analysis based on linear regression models using the respondents' attributes and personality traits. The effects were consistently correlated with a sense of familial support, with the effect sizes varying according to country (US &gt; Japan &gt; Canada). Attributes that positively contributed to the message being more effective were higher agreeableness, lower Machiavellianism, lower psychopathy, and being a woman. Although personal fear about COVID-19 moderated the message effects, concern about the threats to relatives and family boosted the effects. Although the effect sizes were influenced by external factors, the results suggested that our proposed framework for information provision has the potential to be applied to a wider variety of risk-related topics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632847/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
25468 5001 비임상 COVID pneumonia Term covid pneumonia abstract 코비드 폐렴 78884 10.1186/s12967-022-03660-9 Efficacy and safety of Treamid in the rehabilitation of patients after COVID-19 pneumonia: a phase 2, randomized, double-blind, placebo-controlled trial Evgeny Bazdyrev@@@Maria Panova@@@Maria Brachs@@@Elena Smolyarchuk@@@Daria Tsygankova@@@Liudmila Gofman@@@Yana Abdyusheva@@@Fedor Novikov 202211 Article PMC {{{ Abstract }}} !!{{ Background: }} Many patients who recovered from COVID are still suffering from pulmonary dysfunction that can be persistent even for months after infection. Therefore, treatment to prevent irreversible impairment of lung function is needed. Treamid (bisamide derivative of dicarboxylic acid, BDDA) was shown to have anti-inflammatory and antifibrotic effects in animal models of pulmonary fibrosis. This study was designed to assess the safety, tolerability, and efficacy of Treamid in the rehabilitation of patients after COVID pneumonia. The aim was to establish whether Treamid could be effective in ameliorating post-COVID sequelae. !!{{ Methods: }} The phase 2, randomized, double-blind, placebo-controlled clinical trial was done at 8 medical centers in Russia. Patients with a diagnosis of COVID in the past medical history (with the first symptoms of COVID appear no earlier than 2 months before screening) and having fibrotic changes in the lungs, decreased lung function (percentage of predicted FVC and/or DLCO &lt; 80%), and moderate or severe dyspnea according to mMRC scale were enrolled and randomly assigned in a 1:1 ratio (stratified by the initial degree of lung damage, age, and concomitant chronic diseases) by use of interactive responsive technology to peroral administration of Treamid 50 mg or placebo once a day for 4 weeks. The primary outcome was the proportion of patients who achieved clinically significant improvement in FVC and/or DLCO (defined as a relative increase in FVC of ≥ 10% or a relative increase in FVC in the range of ≥ 5 to &lt; 10% plus a relative increase in DLCO of ≥ 15%) at week 4 compared with baseline. Secondary endpoints included changes from baseline in dyspnea scoring evaluated by the modified Borg and mMRC scales, pulmonary function (FEV 1 , FVC, FEV 1 /FVC ratio, DLCO, TLC, FRC), 6-min walk distance, the overall score of the KBILD questionnaire, and the proportion of patients with a reduction in the degree of lung damage assessed by CT scores. This trial was registered on ClinicalTrials.gov (Identifier: NCT04527354 ). The study was fully funded by PHARMENTERPRISES LLC. !!{{ Results: }} 12 out of 29 patients (41%) in Treamid group achieved clinically significant improvement in FVC and/or DLCO compared to 5 out of 30 patients (17%) in placebo group (p = 0.036). There was a significant decrease of dyspnea according to modified Borg scale observed in the Treamid group (- 0.9 ± 0.7 vs. - 0.4 ± 0.8, p = 0.018). No significant differences in the adverse events were noted. Exploratory analysis of the female population indicated superiority of Treamid over placebo by decreasing dyspnea and the extent of lung damage as well as increasing TLC. !!{{ Conclusions: }} 4 weeks oral administration of 50 mg Treamid was associated with clinically significant improvement in the post-COVID patients, evident by an increase in FVC and/or DLCO as well as decreasing dyspnea. Treamid was well tolerated and can be safely administered to patients discharged after COVID. Treamid was more effective in women visible by superior improvement of COVID sequalae after 4 weeks treatment. Considering that female gender is a risk factor associated with the development of post-COVID symptoms, Treamid might offer a pharmacological treatment for long-term sequalae after COVID and supports further investigation in future clinical trials in post-COVID patients. !!{{ Keywords: }} COVID; Lung fibrosis; Lung function; NCT04527354 ; Post-COVID rehabilitation; SARS-CoV-2; Treamid. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632561/ 78 1479-5876 Journal of Translational Medicine [London] : BioMed Central
25444 5001 비임상 suggested Action suggested abstract None 78883 10.1371/journal.pone.0277183 Cross-cultural comparison of nudging effects for environmental protection: A case-study of risk-averse attitudes toward disposable plastics Hidenori Komatsu@@@Hiromi Kubota@@@Nobuyuki Tanaka@@@Mariah Griffin@@@Jennifer Link@@@Glenn Geher@@@Maryanne L Fisher 202211 Article PMC {{{ Abstract }}} !! Disposable plastics are drawing considerable attention as a source of environmental risk despite their benefits in daily life. Banning the use of disposable plastics could increase other types of risks, which may damage the public good in the long run. Considering the trade-off of the risks and benefits, one way to improve social welfare is to conduct proper recycling and to continue using plastics but limit them to essential use, avoiding an unnecessary ban. A potential barrier to such a policy might be risk-averse attitudes toward actions that are perceived to threaten future generations, which is a well-known phenomenon. We previously designed a framework for information provision using messages that remind individuals about familial support, which had significant effects in multiple countries on increasing positive attitudes toward air pollution caused by industrialization. We hypothesized that this information provision could also be effective for disposable plastic use. Thus, we conducted a randomized controlled trial via online surveys in Japan, Canada, and the US to identify the effects of our designed messages about recycling on increasing positive attitudes toward disposable plastics. The intervention effects were measured by the difference-in-difference method and panel analysis based on linear regression models using the respondents' attributes and personality traits. The effects were consistently correlated with a sense of familial support, with the effect sizes varying according to country (US &gt; Japan &gt; Canada). Attributes that positively contributed to the message being more effective were higher agreeableness, lower Machiavellianism, lower psychopathy, and being a woman. Although personal fear about COVID-19 moderated the message effects, concern about the threats to relatives and family boosted the effects. Although the effect sizes were influenced by external factors, the results suggested that our proposed framework for information provision has the potential to be applied to a wider variety of risk-related topics. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9632847/ 49 1932-6203 PLoS ONE San Francisco, CA : Public Library of Science.
4812 5001 비임상 determine Action determine abstract None 3546 10.1186/s13063-021-05132-9 Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial 202103 Study Protocol PMC Background Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2. Methods Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population. Discussion This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis. Trial registration ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s13063-021-05132-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942514/ 54 1745-6215 Trials [London] : BioMed Central
4348 5001 비임상 Traditional Chinese medicine Term traditional chinese medicine abstract 중국의_의학 2304 10.1016/j.jep.2021.114838 Inhibitory effects and mechanisms of the anti-covid-19 traditional Chinese prescription, Keguan-1, on acute lung injury Zhaofang Bai@@@Pengyan Li@@@Jincai Wen@@@Yanzhong Han@@@Yuanyuan Cui@@@Yongfeng Zhou@@@Zhuo Shi@@@Shuaishuai Chen@@@Qiang Li@@@Xu Zhao@@@Zhongxia Wang@@@Ruisheng Li@@@Yuming Guo@@@Xiaoyan Zhan@@@Guang Xu@@@Kaixin Ding@@@Jiabo Wang@@@Xiaohe Xiao 202203 Article PMC {{{ Abstract }}} !!{{ Ethnopharmacological relevance: }} Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. !!{{ Aim of the study: }} To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. !!{{ Materials and methods: }} Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. administration of LPS. The levels of inflammatory factors tumour necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. !!{{ Results: }} Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1β, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. !!{{ Conclusion: }} These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases. !!{{ Keywords: }} ALI; COVID-19; Inflammation; Keguan-1; Pulmonary vascular endothelial injury. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590745/ 275 0378-8741 Journal of ethnopharmacology Limerick : Elsevier Sequoia.
4963 5001 비임상 Parkinson&#8217;s disease Term parkinson’s disease author 파킨슨병 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4964 5001 비임상 Parkinson’s disease Term parkinson’s disease abstract 파킨슨병 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4084 5001 비임상 caused Action caused abstract None 698 10.1038/s41422-021-00531-8 Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 Shiyu Sun@@@Yueqi Cai@@@Tian-Zhang Song@@@Yang Pu@@@Lin Cheng@@@Hairong Xu@@@Jing Sun@@@Chaoyang Meng@@@Yifan Lin@@@Haibin Huang@@@Fang Zhao@@@Silin Zhang@@@Yu Gao@@@Jian-Bao Han@@@Xiao-Li Feng@@@Dan-Dan Yu@@@Yalan Zhu@@@Pu Gao@@@Haidong Tang@@@Jincun Zhao@@@Zheng Zhang@@@Jiaming Yang@@@Zhenxiang Hu@@@Yang-Xin Fu@@@Yong-Tang Zheng@@@Hua Peng 202107 Clinical Trial PMC Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global crisis, urgently necessitating the development of safe, efficacious, convenient-to-store, and low-cost vaccine options. A major challenge is that the receptor-binding domain (RBD)-only vaccine fails to trigger long-lasting protective immunity if used alone for vaccination. To enhance antigen processing and cross-presentation in draining lymph nodes (DLNs), we developed an interferon (IFN)-armed RBD dimerized by an immunoglobulin fragment (I-R-F). I-R-F efficiently directs immunity against RBD to DLNs. A low dose of I-R-F induces not only high titers of long-lasting neutralizing antibodies (NAbs) but also more comprehensive T cell responses than RBD. Notably, I-R-F provides comprehensive protection in the form of a one-dose vaccine without an adjuvant. Our study shows that the pan-epitope modified human I-R-F (I-P-R-F) vaccine provides rapid and complete protection throughout the upper and lower respiratory tracts against a high-dose SARS-CoV-2 challenge in rhesus macaques. Based on these promising results, we have initiated a randomized, placebo-controlled, phase I/II trial of the human I-P-R-F vaccine (V-01) in 180 healthy adults, and the vaccine appears safe and elicits strong antiviral immune responses. Due to its potency and safety, this engineered vaccine may become a next-generation vaccine candidate in the global effort to overcome COVID-19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280646/ 114 1001-0602 Cell Research Basingstoke, England : Nature Publishing Group.
4965 5001 비임상 participant Patient participant abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
4966 5001 비임상 Participants Patient participant abstract None 5577 10.1186/s12883-021-02248-y Improvements in clinical signs of Parkinson’s disease using photobiomodulation: a prospective proof-of-concept study Ann Liebert@@@Brian Bicknell@@@E-Liisa Laakso@@@Gillian Heller@@@Parastoo Jalilitabaei@@@Sharon Tilley@@@John Mitrofanis@@@Hosen Kiat 202107 Article PMC Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12?weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14?weeks before commencing the same?treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4?weeks of treatment, after 12?weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved ( p <?0.05) with PBM treatment for 12?weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted. Trial registration Australian New Zealand Clinical Trials Registry, registration number: ACTRN12618000038291p , registered on 12/01/2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-021-02248-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249215/ 446 1471-2377 BMC Neurology London : BioMed Central
상품 미리보기
연락처 및 데이터 관리
판매제공처 홈페이지 판매담당자 연락처 이메일
www.vinea.co.kr (주)비네아 010-8703-2109 bongbong@vinea.co.kr
연관 상품
상품명 가격
COVID19 데이터셋 3000000
진단 데이터셋 공개데이터 0
신종인플루엔자 데이터셋 2000000
홍역 데이터셋 3000000
제약 및 취소환불 규정
제약 및 취소/환불 규정 안내
데이터 상품은 디지털화된 상품의 특성상 반품, 취소, 환불 되지 않으나 데이터의 심각한 오류, 상이한 데이터에 한하여 구매자가 요구하는 경우 환불을 진행할 수 있습니다.
상품 Q&A

※ 본인의 글만 수정이 가능하며, 타인의 글에 댓글을 남길 수 없습니다.
※ 댓글이 달린 글은 수정과 삭제가 불가능합니다.

등록된 글이 없습니다.

닫기버튼
해당 문의 내역을 삭제하시겠습니까?

닫기버튼
해당 문의 내역을 삭제하시겠습니까?