利用中药网络药理学和分子对接技术初步探索"清肺排毒汤"抗新型冠状病毒肺炎(coronavirus disease2019,COVID-19)作用机制。结合中国药典(2015版)以及中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems P...利用中药网络药理学和分子对接技术初步探索"清肺排毒汤"抗新型冠状病毒肺炎(coronavirus disease2019,COVID-19)作用机制。结合中国药典(2015版)以及中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)、OMIM(Online Mendelian Inheritance in Man)、GeneCard、STRING等在线数据库,进行一系列网络构建、核心靶点筛选以及信号通路富集分析,最后对重要化合物进行分子对接预测。结果发现,清肺排毒汤化合物-肺炎靶点网络包含292个化合物和相应靶点214个,核心靶点涉及AKT1(AKT serine/threonine kinase 1)、IL6(interleukin 6)、MAPK8(mitogen-activated protein kinase 8)、MAPK1(mitogen-activated protein kinase 1)和JUN(jun proto-oncogene)等。应用GO(Gene Ontology)数据库功能富集分析得到858个GO条目,应用KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库富集筛选得到122条有关通路,其中包含低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)通路、Toll样受体(Toll-like receptors,TLRs)通路等已报道与肺炎相关的通路,也包括T细胞受体(T-cell receptor,TCR)通路等与肺损伤保护相关的通路。分子对接结果显示,清肺排毒汤中药材部分核心化合物对新型冠状病毒(2019-nCoV)的3C类似蛋白酶(3C-like protease,3CLpro)和血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)蛋白具有一定的亲和力。本文初步探索了清肺排毒汤抗COVID-19的作用机制,且预测了其药效物质基础,期待本结果能为进一步确证清肺排毒汤抗COVID-19有效成分和作用机制提供帮助。展开更多
Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury （SCI）, and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by mul...Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury （SCI）, and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by multiple factors. Autophagy can result in cell death, and plays a key role in the development of SCI. It has been recognized that valproic acid （VPA） is neuroprotective in certain experimental animal models, however, the levels of autophagic changes in the process of neuroprotection by VPA treatment following SCI are still unknown. In the present study, we determined the extent of autophagy after VPA treatment in a rat model of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however, Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie-Bresnahan scale, increased the number of ventral horn motoneurons, and reduced myelin sheath damage compared with vehicle-treated animals at 42 days after SCI. Together, our results demonstrated the characteristics of autophagy expression following SCI, and foundthat VPA reduced autophagy and enhanced motor function.展开更多
A test for the wake vortex of a flexible oscillating caudal fin is carried out with Digital Particle Image Velocimetry （DPIV）, and the variation of vortex distance and the vorticity in the range of oscillating frequ...A test for the wake vortex of a flexible oscillating caudal fin is carried out with Digital Particle Image Velocimetry （DPIV）, and the variation of vortex distance and the vorticity in the range of oscillating frequency from 0.704 Hz to 1.17 Hz are analyzed. It is found that with the increase of the oscillating frequency, the vortex distance decreases and the peak of the vorticity increases, When the Strouhal number is smaller than 0.49, a larger thrust component is obtained. The distribution of the velocity circulation and the vortex distance in the different spanwise section of the caudal fin are given, and then the dimension of the vortex ring is determined. The radius of the vortex ring is 79.3 mm and the average velocity circulation is 28152.9 mm2/s at the oscillating frequency of 0.835 Hz. The model of 3-D vortex ring chain of flexible oscillating caudal fin is constructed based on the information of wake vortex field. Finally, an effective analysis method is provided for establishing the relationship of oscillating parameters for the caudal fin and the wake structure and the intrinsic mechanism of efficient fish swimming is investigated.展开更多
BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,ide...BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce int展开更多
文摘利用中药网络药理学和分子对接技术初步探索"清肺排毒汤"抗新型冠状病毒肺炎(coronavirus disease2019,COVID-19)作用机制。结合中国药典(2015版)以及中药系统药理学数据库及分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)、OMIM(Online Mendelian Inheritance in Man)、GeneCard、STRING等在线数据库,进行一系列网络构建、核心靶点筛选以及信号通路富集分析,最后对重要化合物进行分子对接预测。结果发现,清肺排毒汤化合物-肺炎靶点网络包含292个化合物和相应靶点214个,核心靶点涉及AKT1(AKT serine/threonine kinase 1)、IL6(interleukin 6)、MAPK8(mitogen-activated protein kinase 8)、MAPK1(mitogen-activated protein kinase 1)和JUN(jun proto-oncogene)等。应用GO(Gene Ontology)数据库功能富集分析得到858个GO条目,应用KEGG(Kyoto Encyclopedia of Genes and Genomes)数据库富集筛选得到122条有关通路,其中包含低氧诱导因子-1(hypoxia inducible factor-1,HIF-1)通路、Toll样受体(Toll-like receptors,TLRs)通路等已报道与肺炎相关的通路,也包括T细胞受体(T-cell receptor,TCR)通路等与肺损伤保护相关的通路。分子对接结果显示,清肺排毒汤中药材部分核心化合物对新型冠状病毒(2019-nCoV)的3C类似蛋白酶(3C-like protease,3CLpro)和血管紧张素转换酶2(angiotensin-converting enzyme 2,ACE2)蛋白具有一定的亲和力。本文初步探索了清肺排毒汤抗COVID-19的作用机制,且预测了其药效物质基础,期待本结果能为进一步确证清肺排毒汤抗COVID-19有效成分和作用机制提供帮助。
基金supported by Special Funds for the Introduction and Development of Talents of Shanxi Province, China
文摘Secondary damage is a critical determinant of the functional outcome in patients with spinal cord injury （SCI）, and involves multiple mechanisms of which the most important is the loss of nerve cells mediated by multiple factors. Autophagy can result in cell death, and plays a key role in the development of SCI. It has been recognized that valproic acid （VPA） is neuroprotective in certain experimental animal models, however, the levels of autophagic changes in the process of neuroprotection by VPA treatment following SCI are still unknown. In the present study, we determined the extent of autophagy after VPA treatment in a rat model of SCI. We found that both the mRNA and protein levels of Beclin-1 and LC3 were significantly increased at 1, 2, and 6 h after SCI and peaked at 2 h; however, Western blot showed that autophagy was markedly decreased by VPA treatment at 2 h post-injury. Besides, post-SCI treatment with VPA improved the Basso-Beattie-Bresnahan scale, increased the number of ventral horn motoneurons, and reduced myelin sheath damage compared with vehicle-treated animals at 42 days after SCI. Together, our results demonstrated the characteristics of autophagy expression following SCI, and foundthat VPA reduced autophagy and enhanced motor function.
基金supported by the National Natural Science Foundation of China(Grant No.50879031)the Key laboratory of Jiangsu Province(Grant No.CT0701)
文摘A test for the wake vortex of a flexible oscillating caudal fin is carried out with Digital Particle Image Velocimetry （DPIV）, and the variation of vortex distance and the vorticity in the range of oscillating frequency from 0.704 Hz to 1.17 Hz are analyzed. It is found that with the increase of the oscillating frequency, the vortex distance decreases and the peak of the vorticity increases, When the Strouhal number is smaller than 0.49, a larger thrust component is obtained. The distribution of the velocity circulation and the vortex distance in the different spanwise section of the caudal fin are given, and then the dimension of the vortex ring is determined. The radius of the vortex ring is 79.3 mm and the average velocity circulation is 28152.9 mm2/s at the oscillating frequency of 0.835 Hz. The model of 3-D vortex ring chain of flexible oscillating caudal fin is constructed based on the information of wake vortex field. Finally, an effective analysis method is provided for establishing the relationship of oscillating parameters for the caudal fin and the wake structure and the intrinsic mechanism of efficient fish swimming is investigated.
基金Supported by National Natural Science Foundation of China,No.82374449China Postdoctoral Science Foundation,No.2023M731782+1 种基金Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB806Jiangsu Province Postgraduate Scientific Research and Innovation Plan,No.KYCX23_2136.
文摘BACKGROUND Constipation,a highly prevalent functional gastrointestinal disorder,induces a significant burden on the quality of patients'life and is associated with substantial healthcare expenditures.Therefore,identifying efficient therapeutic modalities for constipation is of paramount importance.Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms.Consequently,we postulate that hydrogen therapy,an emerging and promising intervention,can serve as a safe and efficacious treatment for constipation.AIM To determine whether hydrogen-rich water(HRW)alleviates constipation and its potential mechanism.METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats.Rats freely consumed HRW,and were recorded their 24 h total stool weight,fecal water content,and charcoal propulsion rate.Fecal samples were subjected to 16S rDNA gene sequencing.Serum non-targeted metabolomic analysis,malondialdehyde,and superoxide dismutase levels were determined.Colonic tissues were stained with hematoxylin and eosin,Alcian blue-periodic acid-Schiff,reactive oxygen species(ROS)immunofluorescence,and immunohistochemistry for cell growth factor receptor kit(c-kit),PGP 9.5,sirtuin1(SIRT1),nuclear factor-erythroid-2-related factor 2(Nrf2),and heme oxygenase-1(HO-1).Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1,Nrf2 and HO-1.A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor,EX527,into constipated rats.NCM460 cells were induced with H2O2 and treated with the metabolites to evaluate ROS and SIRT1 expression.RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h,fecal water content,charcoal propulsion rate,thickness of the intestinal mucus layer,c-kit expression,and the number of intestinal neurons.HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism.HRW could also reduce int
