OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the...OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.展开更多
由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD-like receptor family pyrin domain-containing protein 3)炎症小体在多种疾病过程中都发挥了关键作用.作为炎症反应的核心,NLRP3炎症小体可能为各种炎症性疾病的治疗提供新的靶点...由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD-like receptor family pyrin domain-containing protein 3)炎症小体在多种疾病过程中都发挥了关键作用.作为炎症反应的核心,NLRP3炎症小体可能为各种炎症性疾病的治疗提供新的靶点.泛素化作为一种多功能翻译后修饰,在NLRP3介导的炎症免疫反应中起着关键的调节作用.通过对NLRP3炎症小体的组成、结构及功能,泛素化过程,泛素化与去泛素化对NLRP3炎症小体的正、负性调控的详细阐述,对NLRP3泛素化靶向治疗的前景与现状深入分析,为炎症性疾病的治疗提供新思路.展开更多
文章从教学手段、教学目标、教学方法、教法举例等方面,论述了基于慕课的疑探教学法在《伤寒论》课程教学中的应用,论证了《伤寒论》课程知识特点和高等中医院校教学条件以及学生自身素养与疑探教学法的高度适配性,提出了设疑自探、解...文章从教学手段、教学目标、教学方法、教法举例等方面,论述了基于慕课的疑探教学法在《伤寒论》课程教学中的应用,论证了《伤寒论》课程知识特点和高等中医院校教学条件以及学生自身素养与疑探教学法的高度适配性,提出了设疑自探、解疑合探、质疑再探等教学环节的具体实施步骤和方法,并以《伤寒论》大青龙汤证为例予以说明。通过《伤寒论》课程疑探式教学实践与探索,认为《伤寒论》课程引入基于慕课(Massive Open Online Course,MOOC)的疑探教学法,能够彰显"以学生为中心"的教学理念,将课堂空间充分向学生思维开放,使学生处于不断思考、不断质疑、不断探究的学习状态,有效激发学生学习兴趣,克服学习倦怠,增强学习的主动性和积极性,培养学生的问题意识和创新能力。展开更多
基金the National Natural Science Foundation of China:Study on the Biological Basis of Jiawei Danzhi Xiaoyaosan in Treatment of Depression based on Network Pharmacology and Proteomics(No.81973739)Natural Science Excellent Youth Fund of Henan Province:the Mechanism of Baicalin Regulates the GSK3B-Mediated Axoplasmic Transport in the Treatment of Depression(No.202300410249)+1 种基金Science and Technology Research Project of Henan Province:Study on the Antidepressant Mechanism of Jiawei Danzhi Xiaoyaosan based on the NOD-like Receptor Thermal Protein Domainassociated Protein and Tripartite Motif-containing Protein 31 Ubiquitination Pathway(No.222102310233)Study on the Mechanism of Jiawei Danzhi Xiaoyaosan in the Treatment of Depression by Regulating M1/M2 Polarization and Microglia Autophagy(No.232102310419)。
文摘OBJECTIVE:To reveal the antidepressant mechanisms of Jiawei DanZhiXiaoYaoSan(加味丹栀逍遥散,JD)in chronic unpredictable mild stress(CUMS)-induced depression in mice.METHODS:Using the CUMS mouse model of depression,the antidepressant effects of JD were assessed using the sucrose preference test(SPT),forced swimming test(FST),and tail suspension test(TST).Tandem mass tag(TMT)-based quantitative proteomic analysis of the brain was performed following JD treatment.Hierarchical clustering,Gene Ontology function annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and protein-protein interactions(PPIs)were used to analyze differentially expressed proteins(DEPs),which were further validated using quantitative real-time polymerase chain reaction(qR T-PCR)and Western blotting.RESULTS:Behavioral tests confirmed the antidepressant effects of JD,and bioinformatics analysis revealed 59 DEPs,including 33 up-regulated and 26 down-regulated proteins,between the CUMS and JD-M groups.KEGG and PPI analyses revealed that neurofilament proteins and the Ras signaling pathway may be key targets of JD in the treatment of depression.q RTPCR and Western blotting results demonstrated that CUMS reduced the protein expression of neurofilament light(NEFL)and medium(NEFM)and inhibited the phosphorylation of extracellular regulated kinase 1/2(ERK1/2),whereas JD promoted the phosphorylation of ERK1/2 and up-regulated the protein expression of NEFL and NEFM.CONCLUSIONS:The antidepressant mechanism of JD may be related to the up-regulation of p-ERK1/2 and neurofilament proteins.
文摘由于能被多种类型的病原体或危险信号所激活,NLRP3(NOD-like receptor family pyrin domain-containing protein 3)炎症小体在多种疾病过程中都发挥了关键作用.作为炎症反应的核心,NLRP3炎症小体可能为各种炎症性疾病的治疗提供新的靶点.泛素化作为一种多功能翻译后修饰,在NLRP3介导的炎症免疫反应中起着关键的调节作用.通过对NLRP3炎症小体的组成、结构及功能,泛素化过程,泛素化与去泛素化对NLRP3炎症小体的正、负性调控的详细阐述,对NLRP3泛素化靶向治疗的前景与现状深入分析,为炎症性疾病的治疗提供新思路.
文摘文章从教学手段、教学目标、教学方法、教法举例等方面,论述了基于慕课的疑探教学法在《伤寒论》课程教学中的应用,论证了《伤寒论》课程知识特点和高等中医院校教学条件以及学生自身素养与疑探教学法的高度适配性,提出了设疑自探、解疑合探、质疑再探等教学环节的具体实施步骤和方法,并以《伤寒论》大青龙汤证为例予以说明。通过《伤寒论》课程疑探式教学实践与探索,认为《伤寒论》课程引入基于慕课(Massive Open Online Course,MOOC)的疑探教学法,能够彰显"以学生为中心"的教学理念,将课堂空间充分向学生思维开放,使学生处于不断思考、不断质疑、不断探究的学习状态,有效激发学生学习兴趣,克服学习倦怠,增强学习的主动性和积极性,培养学生的问题意识和创新能力。