Objective:To observe the regulatory impact of immune inhibitors on T cells in rats.Method:Forty SD rats were selected and randomly divided into experimental group and control group.Rapamycin(SRL)0.4 mg/d to fill the s...Objective:To observe the regulatory impact of immune inhibitors on T cells in rats.Method:Forty SD rats were selected and randomly divided into experimental group and control group.Rapamycin(SRL)0.4 mg/d to fill the stomach of the former one,saline lavage was used with the latter one for two weeks.Using flow cytometry to detect the two groups of rats with spleen and thymus level of CD4+CD25+T cells;and the spleen cells FoxP3 mRNA expression;Using ELISA method to detect TGF-β,IL-10 levels.Results:The peripheral blood,spleen and thymus of CD4+CD25+T cells accounted for the proportion of mononuclear cells were significantly higher than that of control group(P<0.05);FoxP3 mRNA expression quantity also significantly higher than the control group(P<0.05);Experimental TGF-βin rats,IL-10 levels are significantly higher than control group(P<0.05).Conclusions:Immune inhibitors can regulatory CD4+CD25+foxp3+T cells in rats,a single nuclear cell proportion increase,shows that it can induce rat CD4+CD25+foxp3+regulatory T cells proliferation.展开更多
BACKGROUND:Regulatory T cells(Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and the...BACKGROUND:Regulatory T cells(Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases,but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation. DATA SOURCES:Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors’ laboratory. RESULTS:We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function,including using histone deacetylase(HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression,induction of Treg-sparing apoptosis via Nur77,and identification of the co-inhibitory molecule herpes virus entry mediator(HVEM) as an effector molecule for Treg function. CONCLUSION:Regulation of Treg function will definitely provide us very promising tools to achieve clinical tolerance in the future.展开更多
Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy me...Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.展开更多
The signal transduction system of microorganisms helps them adapt to changes in their complex living environment.Two-component system(TCS)is a representative signal transduction system that plays a crucial role in reg...The signal transduction system of microorganisms helps them adapt to changes in their complex living environment.Two-component system(TCS)is a representative signal transduction system that plays a crucial role in regulating cellular communication and secondary metabolism.In Gram-negative bacteria,an unorthodox TCS consist-ing of histidine kinase protein GacS(initially called LemA)and response regulatory protein GacA is widespread.It mainly regulates various physiological activities and behaviors of bacteria,such as quorum sensing,secondary metabolism,biofilm formation and motility,through the Gac/Rsm(Regulator of secondary metabolism)signaling cascade pathway.The global regulatory ability of GacS/GacA in cell physiological activities makes it a potential research entry point for developing natural products and addressing antibiotic resistance.In this review,we summarize the progress of research on GacS/GacA from various perspectives,including the reaction mechanism,related regulatory pathways,main functions and GacS/GacA-mediated applications.Hopefully,this review will facilitate further research on GacS/GacA and promote its application in regulating secondary metabolism and as a therapeutic target.展开更多
目的:探讨槲皮素对糖尿病肾病的影响及该影响与肾小球周期素激酶抑制剂P27的关系。方法:腹腔注射链脲佐菌素建立糖尿病(DM)模型,分别以生理盐水或槲皮素(100 mg·kg1·d-1)灌胃8周。蛋白印迹(Western杂交)法测定肾小球裂解液P2...目的:探讨槲皮素对糖尿病肾病的影响及该影响与肾小球周期素激酶抑制剂P27的关系。方法:腹腔注射链脲佐菌素建立糖尿病(DM)模型,分别以生理盐水或槲皮素(100 mg·kg1·d-1)灌胃8周。蛋白印迹(Western杂交)法测定肾小球裂解液P27蛋白水平,ELISA法测定肾小球裂解液细胞外基质(ECM)蛋白(Ⅳ型胶原及纤维连接蛋白)和尿白蛋白。结果:DM 8周大鼠肾小球P27水平增高,ECM蛋白水平增加,尿白蛋白排泄增多,肾质量/体质量比值增高。槲皮素灌胃8周显著降低DM大鼠。肾小球P27水平(10.6±3.1 vs 18.5±4.3,P<0.01)和ECM蛋白水平,减少尿白蛋白排泄[(17.62±3.02)vs(39.62±3.68)μg/24 h,P<0.01],降低DM大鼠肾质量/体质量比值(11.35±1.76 vs 14.87±2.02,P<0.01)。槲皮素不改变DM大鼠血糖水平。结论:槲皮素可能通过降低肾小球P27水平改善糖尿病肾病症状。展开更多
目的探讨肝移植患者在脓毒症不同阶段外周血调节性T细胞(Treg)比例和功能的变化。方法选取自2009年1月至2010年12月期间在中山大学附属第三医院行外科手术,术后合并脓毒症的47例患者作为研究对象,根据手术方式和美国胸科和危重症医师协...目的探讨肝移植患者在脓毒症不同阶段外周血调节性T细胞(Treg)比例和功能的变化。方法选取自2009年1月至2010年12月期间在中山大学附属第三医院行外科手术,术后合并脓毒症的47例患者作为研究对象,根据手术方式和美国胸科和危重症医师协会制订的脓毒症诊断和分期标准指南分为4组:肝移植脓毒症组(sepsis after liver transplantation group,TS组;11例)、肝移植严重脓毒症组(severe sepsis after liver transplantation group,TSS组;10例)、非肝移植脓毒症组(sepsis without liver transplantation group,NTS组;15例)、非肝移植严重脓毒症组(severe sepsis without liver transplantation group,NTSS组;11例),另外选取20名健康正常人作为健康对照组。4组脓毒症患者通过急性生理和慢性健康评估(acute physiology and chronic health evaluation,APACHE)Ⅱ和感染相关的序贯器官衰竭评估(sequential organ failure assessment,SOFA)来评价与比较脓毒症严重程度。分别采集各组研究对象的外周血,采用流式细胞术检测CD4+CD25+Foxp3+调节性T细胞比例(Treg%),采用荧光定量逆转录聚合酶链反应检测Foxp3信使核糖核酸(messenger RNA,mRNA)。结果 TSS和NTSS组的APACHEⅡ评分、SOFA评分均高于TS组和NTS组(均为P<0.01),且TS组的APACHEⅡ评分高于NTS组,TSS组的APACHEⅡ评分和SOFA评分均高于NTSS组(均为P<0.01)。与健康对照组比较,NTS组Treg%明显降低(P<0.001),NTSS组明显升高(P=0.003);而TS组与健康对照组相比差异无统计学意义(P=0.398),TSS组也高于健康对照组(P=0.006),但变化幅度不如NTSS组显著。4组脓毒症组的组间比较发现,NTSS组患者Treg%显著高于NTS组(P<0.01),而TSS组与TS组两组比较差异无统计学意义(P=0.099),NTS组患者Treg%低于TS组(P=0.05),而NTSS组则显著高于TSS组(P=0.002)。与健康对照组比较,NTSS组的Foxp3 mRNA表达显著升高,差异有统计学意义(P<0.05)。4组脓毒症组的组间比较发现,TSS组和NTSS组Foxp3 mRNA表达值均高于TS组和TSS组,但移植组内(TS组与TSS组)的差异没有非移植组(NTS组与NTSS组)显著(分别为P=0.038、P<0.001);另外NTSS组的Foxp3 mRNA表达显著高于TSS组(P=0.012)。结论免疫抑制剂的应用使移植患者在发生脓毒症时Treg的比例和功能的变化有别于普通人群,评估机体免疫状态时需要综合多个免疫指标。展开更多
基金supported by Hebei Province Baoding City Science and Technology Project(No:13ZF074)
文摘Objective:To observe the regulatory impact of immune inhibitors on T cells in rats.Method:Forty SD rats were selected and randomly divided into experimental group and control group.Rapamycin(SRL)0.4 mg/d to fill the stomach of the former one,saline lavage was used with the latter one for two weeks.Using flow cytometry to detect the two groups of rats with spleen and thymus level of CD4+CD25+T cells;and the spleen cells FoxP3 mRNA expression;Using ELISA method to detect TGF-β,IL-10 levels.Results:The peripheral blood,spleen and thymus of CD4+CD25+T cells accounted for the proportion of mononuclear cells were significantly higher than that of control group(P<0.05);FoxP3 mRNA expression quantity also significantly higher than the control group(P<0.05);Experimental TGF-βin rats,IL-10 levels are significantly higher than control group(P<0.05).Conclusions:Immune inhibitors can regulatory CD4+CD25+foxp3+T cells in rats,a single nuclear cell proportion increase,shows that it can induce rat CD4+CD25+foxp3+regulatory T cells proliferation.
基金This work is supported by NIH grant R01-AI 54720- 01 to WWH.
文摘BACKGROUND:Regulatory T cells(Tregs) play crucial roles in both induction and maintenance of tolerance. This active immune regulation may contribute not only to the control of immune responses to self-antigens and thereby prevent autoimmune diseases,but also the control of responses to non-self molecules in adaptive immunity. Numerous experimental and clinical studies indicate that manipulating the balance between regulatory and responder T cells is an effective strategy to control immune responsiveness after transplantation. DATA SOURCES:Literature search was conducted using PubMed on the related subjects. Part of the material was based on the most recent work in the authors’ laboratory. RESULTS:We propose some new strategies to achieve transplant tolerance in rodent animals via manipulating Treg function,including using histone deacetylase(HDAC) inhibitor to regulate Foxp3 transcription and enhance Treg suppression,induction of Treg-sparing apoptosis via Nur77,and identification of the co-inhibitory molecule herpes virus entry mediator(HVEM) as an effector molecule for Treg function. CONCLUSION:Regulation of Treg function will definitely provide us very promising tools to achieve clinical tolerance in the future.
基金supported by National Natural Science Foundation of China(NSFC)(No.81773637,82141216,U1803122)Chunhui Program-Cooperative Research Project of the Ministry of Education+2 种基金Shenyang Young and Middle-aged Innovative Talents Support Program(RC210446,China)Liaoning Province Natural Science Foundation(Nos.2022-MS-241,2020-MZLH-31,China)support from National-Local Joint Engineering Research Center for Molecular Biotechnology of Fujian&Taiwan TCM,Fujian Key Laboratory of Chinese Materia Medica,Fujian University Key Laboratory for Research and Development of TCM Resources,at Fujian University of Traditional Chinese Medicine。
文摘Reprogramming of energy metabolism is one of the basic characteristics of cancer and has been proved to be an important cancer treatment strategy.Isocitrate dehydrogenases(IDHs)are a class of key proteins in energy metabolism,including IDH1,IDH2,and IDH3,which are involved in the oxidative decarboxylation of isocitrate to yield a-ketoglutarate(a-KG).Mutants of IDH1 or IDH2 can produce D-2-hydroxyglutarate(D-2HG)with a-KG as the substrate,and then mediate the occurrence and development of cancer.At present,no IDH3 mutation has been reported.The results of pan-cancer research showed that IDH1 has a higher mutation frequency and involves more cancer types than IDH2,implying IDH1 as a promising anti-cancer target.Therefore,in this review,we summarized the regulatory mechanisms of IDH1 on cancer from four aspects:metabolic reprogramming,epigenetics,immune microenvironment,and phenotypic changes,which will provide guidance for the understanding of IDH1 and exploring leading-edge targeted treatment strategies.In addition,we also reviewed available IDH1 inhibitors so far.The detailed clinical trial results and diverse structures of preclinical candidates illustrated here will provide a deep insight into the research for the treatment of IDH1-related cancers.
基金supported by the National Natural Science Foundation of China(42176108,31870023)the Young Taishan Scholars Program of Shandong Province(tsqn202103029)the Fundamental Research Funds for the Central Universities(201941009).
文摘The signal transduction system of microorganisms helps them adapt to changes in their complex living environment.Two-component system(TCS)is a representative signal transduction system that plays a crucial role in regulating cellular communication and secondary metabolism.In Gram-negative bacteria,an unorthodox TCS consist-ing of histidine kinase protein GacS(initially called LemA)and response regulatory protein GacA is widespread.It mainly regulates various physiological activities and behaviors of bacteria,such as quorum sensing,secondary metabolism,biofilm formation and motility,through the Gac/Rsm(Regulator of secondary metabolism)signaling cascade pathway.The global regulatory ability of GacS/GacA in cell physiological activities makes it a potential research entry point for developing natural products and addressing antibiotic resistance.In this review,we summarize the progress of research on GacS/GacA from various perspectives,including the reaction mechanism,related regulatory pathways,main functions and GacS/GacA-mediated applications.Hopefully,this review will facilitate further research on GacS/GacA and promote its application in regulating secondary metabolism and as a therapeutic target.
文摘目的:探讨槲皮素对糖尿病肾病的影响及该影响与肾小球周期素激酶抑制剂P27的关系。方法:腹腔注射链脲佐菌素建立糖尿病(DM)模型,分别以生理盐水或槲皮素(100 mg·kg1·d-1)灌胃8周。蛋白印迹(Western杂交)法测定肾小球裂解液P27蛋白水平,ELISA法测定肾小球裂解液细胞外基质(ECM)蛋白(Ⅳ型胶原及纤维连接蛋白)和尿白蛋白。结果:DM 8周大鼠肾小球P27水平增高,ECM蛋白水平增加,尿白蛋白排泄增多,肾质量/体质量比值增高。槲皮素灌胃8周显著降低DM大鼠。肾小球P27水平(10.6±3.1 vs 18.5±4.3,P<0.01)和ECM蛋白水平,减少尿白蛋白排泄[(17.62±3.02)vs(39.62±3.68)μg/24 h,P<0.01],降低DM大鼠肾质量/体质量比值(11.35±1.76 vs 14.87±2.02,P<0.01)。槲皮素不改变DM大鼠血糖水平。结论:槲皮素可能通过降低肾小球P27水平改善糖尿病肾病症状。
文摘目的探讨肝移植患者在脓毒症不同阶段外周血调节性T细胞(Treg)比例和功能的变化。方法选取自2009年1月至2010年12月期间在中山大学附属第三医院行外科手术,术后合并脓毒症的47例患者作为研究对象,根据手术方式和美国胸科和危重症医师协会制订的脓毒症诊断和分期标准指南分为4组:肝移植脓毒症组(sepsis after liver transplantation group,TS组;11例)、肝移植严重脓毒症组(severe sepsis after liver transplantation group,TSS组;10例)、非肝移植脓毒症组(sepsis without liver transplantation group,NTS组;15例)、非肝移植严重脓毒症组(severe sepsis without liver transplantation group,NTSS组;11例),另外选取20名健康正常人作为健康对照组。4组脓毒症患者通过急性生理和慢性健康评估(acute physiology and chronic health evaluation,APACHE)Ⅱ和感染相关的序贯器官衰竭评估(sequential organ failure assessment,SOFA)来评价与比较脓毒症严重程度。分别采集各组研究对象的外周血,采用流式细胞术检测CD4+CD25+Foxp3+调节性T细胞比例(Treg%),采用荧光定量逆转录聚合酶链反应检测Foxp3信使核糖核酸(messenger RNA,mRNA)。结果 TSS和NTSS组的APACHEⅡ评分、SOFA评分均高于TS组和NTS组(均为P<0.01),且TS组的APACHEⅡ评分高于NTS组,TSS组的APACHEⅡ评分和SOFA评分均高于NTSS组(均为P<0.01)。与健康对照组比较,NTS组Treg%明显降低(P<0.001),NTSS组明显升高(P=0.003);而TS组与健康对照组相比差异无统计学意义(P=0.398),TSS组也高于健康对照组(P=0.006),但变化幅度不如NTSS组显著。4组脓毒症组的组间比较发现,NTSS组患者Treg%显著高于NTS组(P<0.01),而TSS组与TS组两组比较差异无统计学意义(P=0.099),NTS组患者Treg%低于TS组(P=0.05),而NTSS组则显著高于TSS组(P=0.002)。与健康对照组比较,NTSS组的Foxp3 mRNA表达显著升高,差异有统计学意义(P<0.05)。4组脓毒症组的组间比较发现,TSS组和NTSS组Foxp3 mRNA表达值均高于TS组和TSS组,但移植组内(TS组与TSS组)的差异没有非移植组(NTS组与NTSS组)显著(分别为P=0.038、P<0.001);另外NTSS组的Foxp3 mRNA表达显著高于TSS组(P=0.012)。结论免疫抑制剂的应用使移植患者在发生脓毒症时Treg的比例和功能的变化有别于普通人群,评估机体免疫状态时需要综合多个免疫指标。
