This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profi...This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profiles from OA patients and healthy controls were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified and intersected with autophagy-related genes from the Human Autophagy Database to pinpoint OA-specific autophagy candidates.Functional enrichment analyses via GO and KEGG highlighted involvement in nutrient response,apoptosis,and PI3K-Akt/FoxO signaling pathways.Core genes were prioritized using machine learning algorithms combined with protein-protein interaction(PPI)network analysis,followed by diagnostic validation in an independent cohort.Molecular docking and 100-ns molecular dynamics simulations were conducted to assess the binding stability between Eucommin A and the core targets.Interaction mechanisms were characterized using root mean square deviation(RMSD),root mean square fluctuation(RMSF),radius of gyration(Rg),and MM/GBSA binding free energy calculations.Among 2436 DEGs,56 were autophagy-related and significantly enriched in key biological processes.Machine learning identified EGFR,MAPK3,and MAPK8 as hub genes,with EGFR and MAPK8 exhibiting significant diagnostic value(AUC>0.5).Eucommin A demonstrated strong binding affinity to EGFR and MAPK8 via hydrogen bonding and hydrophobic interactions.Molecular dynamics simulations confirmed stable ligand-target complexes and favorable binding free energy profiles.These findings suggested EGFR and MAPK8 as diagnostic biomarkers for OA-related autophagy.Moreover,Eucommin A exerted multi-target therapeutic effects by stabilizing these autophagy-related proteins,proposing a novel strategy for OA treatment through modulation of autophagy.展开更多
Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing mi...Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.展开更多
This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A compr...This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.展开更多
Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic p...Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic proportions.Conventional Western medical treatments often come with a range of adverse effects.According to traditional Chinese medicine(TCM),the root cause of HUA lies in the spleen’s insufficient healthy movement,with phlegm,dampness,turbidity,and stasis being symptomatic manifestations.Research has shown that spleen-strengthening herbal remedies can effectively treat HUA by inhibiting uric acid synthesis enzymes,promoting uric acid excretion,reducing inflammation,providing antioxidant benefits,regulating gut microbiota,and modulating cellular processes.Clinical applications have substantiated these findings.Therefore,from the standpoint of symptomatic treatment of HUA,spleen-strengthening therapies hold significant importance and potential.展开更多
In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of t...In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.展开更多
This study aimed to systematically analyze the research status and trends in animal models for gout and hyperuricemia(HUA)through a bibliometric approach.We retrieved relevant literature on animal models of gout and H...This study aimed to systematically analyze the research status and trends in animal models for gout and hyperuricemia(HUA)through a bibliometric approach.We retrieved relevant literature on animal models of gout and HUA from the Web of Science(WOS)database.Utilizing analysis software such as Citespace and VOSviewer,we conducted a comprehensive examination of annual publication trends,contributing countries,institutions,and authors.Our analysis revealed a steady increase in the number of publications in this field.China emerged as the leading country,with 113 publications.Zhen Liu was identified as the most influential author,while Nanjing University stood out as the most influential institution.Keyword analysis elucidated current focal points,uncovering evolving patterns and emerging hotspots within the research landscape.Current research predominantly centered on understanding the pathogenesis and exploring new treatment modalities for gout and HUA.This study offered valuable insights into research trends and hotspots related to animal models for gout and HUA,enabling researchers to stay informed about the latest developments in this field.展开更多
基金Guangzhou University of Chinese Medicine Shenzhen Hospital(Futian)Postdoctoral Foundation。
文摘This study aimed to investigate the role of autophagy-related genes in osteoarthritis(OA)and evaluate the therapeutic potential of Eucommin A,a key lignan component derived from Eucommia ulmoides.Gene expression profiles from OA patients and healthy controls were retrieved from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified and intersected with autophagy-related genes from the Human Autophagy Database to pinpoint OA-specific autophagy candidates.Functional enrichment analyses via GO and KEGG highlighted involvement in nutrient response,apoptosis,and PI3K-Akt/FoxO signaling pathways.Core genes were prioritized using machine learning algorithms combined with protein-protein interaction(PPI)network analysis,followed by diagnostic validation in an independent cohort.Molecular docking and 100-ns molecular dynamics simulations were conducted to assess the binding stability between Eucommin A and the core targets.Interaction mechanisms were characterized using root mean square deviation(RMSD),root mean square fluctuation(RMSF),radius of gyration(Rg),and MM/GBSA binding free energy calculations.Among 2436 DEGs,56 were autophagy-related and significantly enriched in key biological processes.Machine learning identified EGFR,MAPK3,and MAPK8 as hub genes,with EGFR and MAPK8 exhibiting significant diagnostic value(AUC>0.5).Eucommin A demonstrated strong binding affinity to EGFR and MAPK8 via hydrogen bonding and hydrophobic interactions.Molecular dynamics simulations confirmed stable ligand-target complexes and favorable binding free energy profiles.These findings suggested EGFR and MAPK8 as diagnostic biomarkers for OA-related autophagy.Moreover,Eucommin A exerted multi-target therapeutic effects by stabilizing these autophagy-related proteins,proposing a novel strategy for OA treatment through modulation of autophagy.
基金National Natural Science Foundation of China(82170747),and Shanghai Key Laboratory of Traditional Chinese Clinical Medicine(20DZ2272200).
文摘Objective To predict the autophagy-related pathogenesis and key diagnostic genes of diabetic kidney disease(DKD)through bioinformatics analysis,and to identify related Chinese medicines.Methods Data from sequencing microarrays GSE30528,GSE30529,and GSE1009 in the Gene Expression Omnibus(GEO)were employed.Differentially expressed genes(DEGs)with adjusted P<0.05 from GSE30528 and GSE30529 were identified.Combining these DEGs with the human autophagy gene database,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and protein-protein interaction(PPI)network analysis were conducted on the obtained DKD autophagy-related genes.Subsequently,the least absolute shrinkage and selection operator(LASSO)regression and support vector machinerecursive feature elimination(SVM-RFE)algorithms were adopted to select autophagy-related genes.The diagnostic capability of these genes was assessed through analysis with the external validation set from microarray GSE1009,and relevant Chinese medicines were inversely predicted using the SymMap database.Results A total of 2014 DEGs were selected from GSE30528 and GSE30529,leading to the identification of 37 DKD autophagy-related genes.GO analysis indicated 681 biological mechanisms,including autophagy regulation and plasma membrane microdomain activity.KEGG enrichment analysis identified 112 related signaling pathways.PPI network analysis showed a marked enrichment of autophagy-related genes in DKD.Through LASSO regression and SVM-RFE,four core diagnostic genes for autophagy in DKD were identified:protein phosphatase 1 regulatory subunit 15A(PPP1R15A),hypoxia inducible factor 1 alpha subunit(HIF1α),deleted in liver cancer 1(DLC1),and ceroid lipofuscinosis neuronal 3(CLN3).The external validation set demonstrated high diagnostic efficiency for these genes.Finally,146 kinds of potential Chinese medicines were predicted using the SymMap database,with heatclearing and detoxifying medicine and blood-activating and stasis-eliminating medicine accounting for the largest proportion(25/146 and 13/146,respectively).Conclusion This study analyzed and validated bioinformatics sequencing databases to elucidate the potential molecular mechanisms of DKD autophagy and predicted key diagnostic genes,potential therapeutic targets,and related Chinese medicines,laying a solid foundation for clinical research and application.
基金supported by the Key Research and Development Program of Yunnan Science and Technology Department(Grant No.202303AC100326)the National Natural Science Foundation of China(Grant No.81960863)the Education Department of Yunnan Province(Grant No.2023Y0463 and 2024Y380).
文摘This study aimed to systematically evaluate the clinical efficacy of combining wax therapy with conventional drug therapy for rheumatoid arthritis(RA)and to provide evidence supporting its clinical application.A comprehensive search was conducted across PubMed,Cochrane Library,China Biomedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),Wanfang,and VIP databases from their inception to May 2024.Randomized controlled trials(RCTs)investigating the combination of wax therapy and conventional drug therapy for RA were included in the analysis.Statistical analysis was performed using Review Manager 5.3 software.Nine studies,encompassing a total of 843 patients,were included.The results demonstrated that the combination therapy significantly improved clinical efficacy compared to conventional drug therapy alone[RR=1.22,95%CI(1.11,1.34)].Moreover,the combination therapy led to notable improvements in DAS 28 scores[MD=-0.90,95%CI(-1.23,-0.57),P<0.00001],VAS scores[MD=-0.90,95%CI(-1.13,-0.66),P<0.00001],reduction in joint tenderness[MD=-1.27,95%CI(-1.81,-0.72),P<0.00001],decreased duration of morning stiffness[MD=-25.47,95%CI(-34.33,-16.61),P<0.00001],and lowered C-reactive protein levels[MD=-6.29,95%CI(-12.02,-0.57),P<0.05].In conclusion,wax therapy combined with conventional anti-rheumatic drugs significantly enhanced the clinical outcomes for RA patients by alleviating symptoms,reducing joint pain and morning stiffness,and decreasing inflammatory markers more effectively than conventional drug therapy alone.
基金National Natural Science Foundations of China(Grant No.81960863)the Education Department of Yunnan Province(Grant No.2023Y0463 and 2024Y380)Yunnan Clinical Research Center for rheumatism in Traditional Chinese Medicine(Grant No.202405AJ310004).
文摘Hyperuricemia(HUA)is a metabolic disorder characterized by elevated levels of uric acid in the blood,resulting from either increased production or decreased excretion of uric acid.This condition has reached epidemic proportions.Conventional Western medical treatments often come with a range of adverse effects.According to traditional Chinese medicine(TCM),the root cause of HUA lies in the spleen’s insufficient healthy movement,with phlegm,dampness,turbidity,and stasis being symptomatic manifestations.Research has shown that spleen-strengthening herbal remedies can effectively treat HUA by inhibiting uric acid synthesis enzymes,promoting uric acid excretion,reducing inflammation,providing antioxidant benefits,regulating gut microbiota,and modulating cellular processes.Clinical applications have substantiated these findings.Therefore,from the standpoint of symptomatic treatment of HUA,spleen-strengthening therapies hold significant importance and potential.
基金National Natural Science Foundations of China (Grant No. 81960863)the Education Department of Yunnan Province (Grant No. 2023Y0463)。
文摘In the present study, we explored the therapeutic potential of Cang Zhu-Huang Bai (CZ-HB) against rheumatoid arthritis (RA) and elucidated the associated mechanisms. The approach involved a systematic examination of the chemical ingredients of CZ-HB using TCMSP database. Subsequently, we predicted the targets corresponding to the active ingredients through the SwissTargetPrediction database. We constructed a comprehensive drug-ingredient-target network using Cytoscape (v 3.8.0), with the main ingredients of the drugs identified based on their degree values. We conducted a meticulous search across GEO, GeneCards, Therapeutic Target Database (TTD), and PharmGkb databases to identify target proteins associated with RA. The intersection of targets corresponding to the drugs' active ingredients and those associated with RA provided crucial insights. Functional analysis, including GO and KEGG pathway enrichment analyses, was performed on the intersecting targets using R (v 4.2.2). Additionally, a protein-protein interaction (PPI) network of the intersecting targets was constructed using the String platform. The resulting drug-ingredient-target-disease topology network was visualized using Cytoscape (v 3.8.0), and the Cytohubba plugin facilitated the identification of hub genes. The study revealed 35 active ingredients of CZ-HB and their corresponding 673 targets. We identified 14 major active ingredients crucial to the drug’s effects by focusing on the degree values. Furthermore, our investigation uncovered 784 targets associated with RA. Through the intersection of drug and disease targets, we pinpointed 34 active ingredients of CZ-HB capable of acting on 126 targets implicated in RA. The topological network analysis of the intersected genes identified five hub genes. The binding affinity of these hub genes to the 14 primary active ingredients of the drug was confirmed through molecular docking. The enrichment results of the intersecting genes suggested that CZ-HB exerted its anti-RA effects through a multi-component, multi-target, and multi-pathway approach.
基金The National Natural Science Foundation of China(Grant No.82160901)Special Project for Social Development under the Key Research and Development Plan of the Yunnan Provincial Science and Technology Department(Grant No.202403AC100019)supported by Yunnan Key Laboratory of Dai and Yi Medicines(Yunnan University of Chinese Medicine)(Grant No.2024SS24032)。
文摘This study aimed to systematically analyze the research status and trends in animal models for gout and hyperuricemia(HUA)through a bibliometric approach.We retrieved relevant literature on animal models of gout and HUA from the Web of Science(WOS)database.Utilizing analysis software such as Citespace and VOSviewer,we conducted a comprehensive examination of annual publication trends,contributing countries,institutions,and authors.Our analysis revealed a steady increase in the number of publications in this field.China emerged as the leading country,with 113 publications.Zhen Liu was identified as the most influential author,while Nanjing University stood out as the most influential institution.Keyword analysis elucidated current focal points,uncovering evolving patterns and emerging hotspots within the research landscape.Current research predominantly centered on understanding the pathogenesis and exploring new treatment modalities for gout and HUA.This study offered valuable insights into research trends and hotspots related to animal models for gout and HUA,enabling researchers to stay informed about the latest developments in this field.
