BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric ac...BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.展开更多
Objective:To explore the molecular mechanism of Zixinyin oral liquid(ZOL)in the treatment of insomnia.Methods:The compounds and action targets of four herbal medicines in ZOL were collected via Traditional Chinese Med...Objective:To explore the molecular mechanism of Zixinyin oral liquid(ZOL)in the treatment of insomnia.Methods:The compounds and action targets of four herbal medicines in ZOL were collected via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes corresponding to the targets were queried from the UniProt database.Genecards database was searched to screen the related targets of insomnia.A Gene Ontologyfunction enrichment analysis and a Kyoto Encyclopedia of Genes and Genomespathway enrichment analysis were performed by Database for Annotation,Visualization and Integrated Discovery.AutoDock software was used for molecular docking to verify the results of network analysis.Results:A total of 47 effective compounds and 187 potential targets of ZOL were screened out from the four drugs.A total of 2592 disease targets were screened out from the genecards database,and there were 1576 genes whose relevance score≥0.5.46 genes were obtained by taking the intersection of 187 potential targets of ZOL and 1,576 targets of insomnia.A total of 3,405 entries were obtained from Gene Ontologyfunctional enrichment(P<0.05).A total of 195 signaling pathways were obtained through a Kyoto Encyclopedia of Genes and Genomespathway analysis(P<0.05).Tumor necrosis factor,interleukin 17and hypoxia inducible factor-1signaling pathways were closely related to insomnia.The results of molecular docking show that all the core compounds of ZOL had a certain degree of affinity with gamma-aminobutyric acid receptor subunit alpha-1(GABRA1)and tumor necrosis factor-α(TNF-α).Paeoniflorgenone shows the highest affinity with GABRA1,and beta-sitosterol shows the highest affinity withTNF-α.ZOLmay have a therapeutic effect on insomnia through its action on targets such as GABRA1 and TNF-α,meanwhile regulating many signaling pathways.展开更多
文摘BACKGROUND Gamma-aminobutyric acid type A receptor has long been acknowledged as a key target in the pathophysiology of epilepsy.The GABRA1 and GABRG2 genes encode the α1 and γ2 subunits of the gamma-aminobutyric acid type A receptor,a key protein implicated in the development of epilepsy.However,the specific association of the GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 polymorphisms with antiepileptic drug resistance has been elucidated in only a limited number of investigations.AIM To elucidate the association between GABRA1 IVS11+15 A>G rs2279020 and GABRG2 G3145A rs211013 gene mutations and drug resistance in epilepsy patients.METHODS A total of 100 epilepsy patients(50 drug responsive and 50 drug resistant subjects)were recruited and rs2279020-and rs211013-polymorphism analyzed by restriction fragment length polymorphism-polymerase chain reaction technique.RESULTS For GABRA1 rs2279020 polymorphism,AG genotype exhibited risk association with an odds ratio of 0.966(95%confidence interval=0.346-2.698)with P value=0.948;however,this association did not achieve statistical significance(P=0.948).Additionally,a higher risk association was identified with the GG genotype,with an odds ratio of 1.808(P=0.382).GABRG2 rs211013 polymorphism revealed no significant association with drug resistance.CONCLUSION The GABRA1 rs2279020 genetic variation is associated with an increased risk for the AG and GG variants,although this association was not statistically significant.Limited investigations have explored the relevance of genetic variations in epilepsy and drug resistance.Longitudinal research is needed to better understand their significance in epilepsy management and to optimize therapeutic strategies.
基金This work was supported by the Hubei Science and Technology Program(No.2020CFB231)Youth Talent Project of Health Commission of Hubei Province(No.ZY2021Q026)Hubei University of Science and Technology Doctoral Startup Fund Project(No.BK202029).
文摘Objective:To explore the molecular mechanism of Zixinyin oral liquid(ZOL)in the treatment of insomnia.Methods:The compounds and action targets of four herbal medicines in ZOL were collected via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes corresponding to the targets were queried from the UniProt database.Genecards database was searched to screen the related targets of insomnia.A Gene Ontologyfunction enrichment analysis and a Kyoto Encyclopedia of Genes and Genomespathway enrichment analysis were performed by Database for Annotation,Visualization and Integrated Discovery.AutoDock software was used for molecular docking to verify the results of network analysis.Results:A total of 47 effective compounds and 187 potential targets of ZOL were screened out from the four drugs.A total of 2592 disease targets were screened out from the genecards database,and there were 1576 genes whose relevance score≥0.5.46 genes were obtained by taking the intersection of 187 potential targets of ZOL and 1,576 targets of insomnia.A total of 3,405 entries were obtained from Gene Ontologyfunctional enrichment(P<0.05).A total of 195 signaling pathways were obtained through a Kyoto Encyclopedia of Genes and Genomespathway analysis(P<0.05).Tumor necrosis factor,interleukin 17and hypoxia inducible factor-1signaling pathways were closely related to insomnia.The results of molecular docking show that all the core compounds of ZOL had a certain degree of affinity with gamma-aminobutyric acid receptor subunit alpha-1(GABRA1)and tumor necrosis factor-α(TNF-α).Paeoniflorgenone shows the highest affinity with GABRA1,and beta-sitosterol shows the highest affinity withTNF-α.ZOLmay have a therapeutic effect on insomnia through its action on targets such as GABRA1 and TNF-α,meanwhile regulating many signaling pathways.
