Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human ...Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human society worldwide.Conventional strategies,such as renin-angiotensinaldosterone system blockade,blood glucose level control,and bodyweight reduction,may not achieve satisfactory outcomes in many clinical practices for DN management.Notably,due to the multi-target function,Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment.Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines.Signaling pathways involved in glucose/lipid metabolism regulation,antioxidation,anti-inflammation,anti-fibrosis,and podocyte protection have been identified as crucial mechanisms of action.Herein,we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials,systematic reviews,and meta-analyses,with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments.We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.展开更多
microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant exp...microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-ceU communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.展开更多
AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was...AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H202)-induced PC 12 cells by Western blotting. RESULTS: Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK 14, CREBI, IFNG, APR and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-KB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of 1KKct, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION: The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-arB signaling pathway as the key targets and pathways for schisandrin.展开更多
Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitate...Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.展开更多
目的:鉴定六味地黄丸入血入脑化学成分,采用网络药理学方法探讨六味地黄丸治疗阿尔茨海默症(AD)潜在作用机制。方法:通过超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UPLC-LTQ-Orbitrap-MS)技术鉴定入血入脑成分,通过T...目的:鉴定六味地黄丸入血入脑化学成分,采用网络药理学方法探讨六味地黄丸治疗阿尔茨海默症(AD)潜在作用机制。方法:通过超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UPLC-LTQ-Orbitrap-MS)技术鉴定入血入脑成分,通过TCMSP、Swiss Target Prediction、OMIM、GeneCards、TTD、DisGeNET、DrugBank数据库预测成分和疾病作用靶点,通过String数据库、Cytoscape软件筛选核心靶点并构建“成分-靶点-疾病-通路”相互作用网络;采用Metascape数据库对核心靶点进行京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)、基因本体分析(gene ontology,GO)。结果:测得六味地黄丸入血入脑成分21个,涉及AD相关靶点蛋白169个。KEGG共富集175条代谢通路,主要涉及神经活性配体-受体相互作用信号通路、糖尿病并发症中AGE-RAGE信号通路、阿尔茨海默症信号通路等。GO功能富集分析主要涉及突触、细胞对氮化合物反应,G蛋白偶联受体活性等过程。结论:六味地黄丸治疗AD具有多靶点、多通路特点,其可能通过改善体内神经活性配体-受体异常、胰岛素受损等过程进行干预,为进一步实验验证其作用机制提供参考依据。展开更多
Parkinson’s disease(PD),known as one of the most universal neurodegenerative diseases,is a serious threat to the health of the elderly.The current treatment has been demonstrated to relieve symptoms,and the discovery...Parkinson’s disease(PD),known as one of the most universal neurodegenerative diseases,is a serious threat to the health of the elderly.The current treatment has been demonstrated to relieve symptoms,and the discovery of new small-molecule compounds has been regarded as a promising strategy.Of note,the homeostasis of the autolysosome pathway(ALP)is closely associated with PD,and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD.Thus,pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far.In this review,we focus on summarizing several autophagy-associated targets,such as AMPK,m TORC1,ULK1,IMPase,LRRK2,beclin-1,TFEB,GCase,ERRα,C-Abelson,and as well as their relevant small-molecule compounds in PD models,which will shed light on a clue on exploiting more potential targeted small-molecule drugs tracking PD treatment in the near future.展开更多
基金financially supported by General Research Fund from the Research Grant Council,Hong Kong Special Administrative Region(Project code:17152116,China)Health and Medical Research Fund from the Food and Health Bureau,Hong Kong Special Administrative Region(Project codes:15162961,16172751,and 17181101,China)+2 种基金Wong’s Donation(Project code:200006276,China)a donation from the Gaia Family Trust of New Zealand(Project code:200007008,New Zealand)a contract research(Project code:CR-BL03,New Zealand)
文摘Diabetic nephropathy(DN) has been recognized as a severe complication of diabetes mellitus and a dominant pathogeny of end-stage kidney disease,which causes serious health problems and great financial burden to human society worldwide.Conventional strategies,such as renin-angiotensinaldosterone system blockade,blood glucose level control,and bodyweight reduction,may not achieve satisfactory outcomes in many clinical practices for DN management.Notably,due to the multi-target function,Chinese medicine possesses promising clinical benefits as primary or alternative therapies for DN treatment.Increasing studies have emphasized identifying bioactive compounds and molecular mechanisms of reno-protective effects of Chinese medicines.Signaling pathways involved in glucose/lipid metabolism regulation,antioxidation,anti-inflammation,anti-fibrosis,and podocyte protection have been identified as crucial mechanisms of action.Herein,we summarize the clinical efficacies of Chinese medicines and their bioactive components in treating and managing DN after reviewing the results demonstrated in clinical trials,systematic reviews,and meta-analyses,with a thorough discussion on the relative underlying mechanisms and molecular targets reported in animal and cellular experiments.We aim to provide comprehensive insights into the protective effects of Chinese medicines against DN.
文摘microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-ceU communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.
基金supported by the National Natural Science Foundation of China(No.81274004)National Key Technologies R&D Program of China(No.2008BAI51B03)+1 种基金2011’Program for Excellent Scientific and Technological Innovation Team of Jiangsu Higher Education,a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,the Project Program of the State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.JKGZ201107)the Graduate Student Scientific Research Innovation Plan of Jiangsu Higher Education Institutions(No.CXZZ11_0795)
文摘AIM: To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification. METHOD: A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H202)-induced PC 12 cells by Western blotting. RESULTS: Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK 14, CREBI, IFNG, APR and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-KB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of 1KKct, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting. CONCLUSION: The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-arB signaling pathway as the key targets and pathways for schisandrin.
基金Supported by a grant from UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases(No.900142,930143,960103,970074,990490)the National Science and Technology Development Agency of Thailand(Career Development Award ID no.01-38-007)the Thailand Research Fund(BasicResearch Grants ID No.BRG/13/2543.BRG4580020.BRG 4880006)
文摘Plasmodium falciparum(P.falciparum) is responsible for the majority of life-threatening cases of human malaria,causing 1.5-2.7 million annual deaths.The global emergence of drug-resistant malaria parasites necessitates identification and characterisation of novel drug targets and their potential inhibitors.We identified the carbonic anhydrase(CA) genes in P.falciparum.The pfGA gene encodes an α-carbonic anhydrase,a Zn^(2+)-metalloenzme,possessing catalytic properties distinct from that of the human host CA enzyme.The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes.A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions.The structure of the groups substituting the aromatic-ureido-or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides.One derivative,that is,4-(3,4-dichlorophenylureido)thioureidobcnzcnesulfonamide(compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor,and was also the most effective antimalarial compound on the in vitro P.falciparum growth inhibition.The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei,an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria.
文摘目的:鉴定六味地黄丸入血入脑化学成分,采用网络药理学方法探讨六味地黄丸治疗阿尔茨海默症(AD)潜在作用机制。方法:通过超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UPLC-LTQ-Orbitrap-MS)技术鉴定入血入脑成分,通过TCMSP、Swiss Target Prediction、OMIM、GeneCards、TTD、DisGeNET、DrugBank数据库预测成分和疾病作用靶点,通过String数据库、Cytoscape软件筛选核心靶点并构建“成分-靶点-疾病-通路”相互作用网络;采用Metascape数据库对核心靶点进行京都基因与基因组百科全书分析(Kyoto encyclopedia of genes and genomes,KEGG)、基因本体分析(gene ontology,GO)。结果:测得六味地黄丸入血入脑成分21个,涉及AD相关靶点蛋白169个。KEGG共富集175条代谢通路,主要涉及神经活性配体-受体相互作用信号通路、糖尿病并发症中AGE-RAGE信号通路、阿尔茨海默症信号通路等。GO功能富集分析主要涉及突触、细胞对氮化合物反应,G蛋白偶联受体活性等过程。结论:六味地黄丸治疗AD具有多靶点、多通路特点,其可能通过改善体内神经活性配体-受体异常、胰岛素受损等过程进行干预,为进一步实验验证其作用机制提供参考依据。
基金financially supported by National Science and Technology Major Project of the Ministry of Science and Technology of the People’s Republic of China(No.2018ZX09735005)National Natural Science Foundation of China(Grant Nos.81803755,81673455 and 81922064)+1 种基金Sichuan University Postdoctoral Research and Development Foundation(Grant No.2020SCU12062,China)Sichuan Science and Technology Program(Grant No.2019JDRC0091,China)。
文摘Parkinson’s disease(PD),known as one of the most universal neurodegenerative diseases,is a serious threat to the health of the elderly.The current treatment has been demonstrated to relieve symptoms,and the discovery of new small-molecule compounds has been regarded as a promising strategy.Of note,the homeostasis of the autolysosome pathway(ALP)is closely associated with PD,and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD.Thus,pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far.In this review,we focus on summarizing several autophagy-associated targets,such as AMPK,m TORC1,ULK1,IMPase,LRRK2,beclin-1,TFEB,GCase,ERRα,C-Abelson,and as well as their relevant small-molecule compounds in PD models,which will shed light on a clue on exploiting more potential targeted small-molecule drugs tracking PD treatment in the near future.