目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NA...目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)中的表达变化进行研究并探讨他们在NAFLD中的作用.方法:将30只Wistar大鼠随机分为正常组和NAFLD模型组,每组各15只.模型组大鼠采用高脂高糖饮食诱导NAFLD,正常组大鼠则给予普通饲料喂养,造模时间总计为16 wk.血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白(highdensity lipoprotein,HDL)和低密度脂蛋白(lowdensity lipoprotein,LDL)的含量采用全自动生化分析仪进行检测;应用PCR技术对肝脏中TRB3及CHOP m RNA水平的改变进行检测;应用免疫组织化学技术对肝脏中TRB3及CHOP蛋白水平的改变进行检测;采用流式细胞仪检测细胞凋亡改变.结果:模型组大鼠血清中TC、TG和LDL含量较正常组大鼠显著升高(P<0.05),而HDL则明显低于正常组(P<0.05);与正常组相比,模型组大鼠肝脏中TRB3及CHOP m RNA水平均显著增加(P<0.05或P<0.01);免疫组织化学结果显示模型组大鼠肝脏中TRB3及CHOP蛋白表达水平较正常组大鼠显著升高(P<0.01);此外流式细胞仪对大鼠肝细胞凋亡进行检测发现,模型组大鼠肝细胞凋亡与正常组相比明显增多.结论:TRB3和CHOP在基因及蛋白水平表达上调可能与高脂高糖诱导的NAFLD的发生发展有关.展开更多
The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of ...The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.展开更多
Objective：To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction（生脉散丹参饮合剂,abbreviated as the Mixture） in the rat model with type 2 diabetic cardiomyopathy （DCM）.Methods：Fo...Objective：To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction（生脉散丹参饮合剂,abbreviated as the Mixture） in the rat model with type 2 diabetic cardiomyopathy （DCM）.Methods：Forty-two SD rats with DCM model,established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet p cells by intraperitoneal injection of high dose streptozotocin （50 mg/kg） once,were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration;the extent of damage in the myocardial subcellular structure was observed by electron microscopy;the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test;the myocardial cell apoptosis was determined by TUNEL;the changes in the mRNA expression levels of thrombospodin-1（TSP-1） and tribbles homolog 3（TRB-3） by real-time quantitative PCR,the expression levels of myocardial TSP-1,tumor growth factorβ1（TGF-β1）,TRB-3,and chymase were detected by immunohistochemistry,and the changes in the expression levels of myocardial TSP-1,active-TGF-β1 （A-TGF-β1） and latent-TGF-β1（L-TGF-β1） protein were tested by Western blotting.Results：Compared with the control group,the myocardial tissue was less damaged,and the extent of damage in the myocardial subcellular structure was less;the collagen fiber content and the cell apoptosis were reduced;the expression levels of TSP-1 mRNA and TRB-3 mRNA,the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and chymase,as well as the average expression levels of the myocardial TSP-1,A-TGFβ1,and L-TGF-β1 protein were decreased in the Mixture group.Conclusion：The Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.展开更多
文摘目的:对Tribbles相关蛋白3(Tribbles related protein 3,TRB3)及CCAAT/增强子结合蛋白同源蛋白(CCAAT/enhancer-binding protein homologous protein,CHOP)在高脂高糖饮食诱导的大鼠非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)中的表达变化进行研究并探讨他们在NAFLD中的作用.方法:将30只Wistar大鼠随机分为正常组和NAFLD模型组,每组各15只.模型组大鼠采用高脂高糖饮食诱导NAFLD,正常组大鼠则给予普通饲料喂养,造模时间总计为16 wk.血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白(highdensity lipoprotein,HDL)和低密度脂蛋白(lowdensity lipoprotein,LDL)的含量采用全自动生化分析仪进行检测;应用PCR技术对肝脏中TRB3及CHOP m RNA水平的改变进行检测;应用免疫组织化学技术对肝脏中TRB3及CHOP蛋白水平的改变进行检测;采用流式细胞仪检测细胞凋亡改变.结果:模型组大鼠血清中TC、TG和LDL含量较正常组大鼠显著升高(P<0.05),而HDL则明显低于正常组(P<0.05);与正常组相比,模型组大鼠肝脏中TRB3及CHOP m RNA水平均显著增加(P<0.05或P<0.01);免疫组织化学结果显示模型组大鼠肝脏中TRB3及CHOP蛋白表达水平较正常组大鼠显著升高(P<0.01);此外流式细胞仪对大鼠肝细胞凋亡进行检测发现,模型组大鼠肝细胞凋亡与正常组相比明显增多.结论:TRB3和CHOP在基因及蛋白水平表达上调可能与高脂高糖诱导的NAFLD的发生发展有关.
基金supported by National Key R&D Program of China(Grant No.2017YFA0205400,China)the National Natural Science Foundation of China(Grant Nos.81530093 and 81773781,China)+43 种基金Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)CAMS Central Public-interest Scientific Institution Basic Research Fund(Grant No.2017PT3104,China)supported by grants of the National Natural Science Foundation of China(Grant No.81874316,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-008,China)supported by grants of from the BBSRC and NWCR(Grant Nos.1088 and 1097,UK)supported by grants of NSF(Grant No.IOS-1456023,USA)NIH(Grant No.NIH R21 CA197317,USA)supported by grants of Ministry of Education,Singapore(Grant Nos.MOE2014-T2-1-012 and 2012-T1-001-036,Singapore)supported by grants from the Health Research Council of New Zealandsupported by a Rutherford Discovery Fellowship from the New Zealand government administered by the Royal Society of New Zealandsupported by Funda??o para a Ciência e a Tecnologia(FCT)Research Center Grant UID/BIM/04773/2013 Centre for Biomedical Research 1334a research grant from Liga Portuguesa Contra o Cancro–Núcleo Regional do Sul(LPCC/NRS,Portugal)a FCT 2014 research grant SFRH/BPD/100434/2014a Pro Regem grant PD/BD/114258/2016(Portugal)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)Innovation Network and the British Heart Foundation(PG/16/44/32146,UK)supported by grants from The Howat Foundation Ltd.(UK),Children with Cancer UK,Bloodwise and the Friends of Paul O'Gorman(UK)supported by grants of P-CREATE from Japan Agency for Medical Research and Developmentsupported by grants from the NIH(NIAID,USA),Alex's Lemonade Stand Foundation(USA)and the Samuel Waxman Cancer Research Foundation(USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)the "Fondation Centaure"(RTRS),which supports a French transplantation research network,the IHU-Cesti project,the DHU Oncogreffefinancial support managed by the National Research Agency via the"Investment into the Future" program(Grant Nos.ANR-10-IBHU-005and ANR-11-LABX-0016-01,France)supported by Nantes Métropole and Région Pays de la Loire(France)supported by grants of the British Heart Foundation(PG/16/44/32146,UK)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by a joint Ph.D studentship beween the A*Star Institute and the University of Sheffield(UK)supported by funding from the National Institutes of Health National Heart,Lung,and Blood Institute(R01HL141745,USA)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by European Marie Sklodowska Curie ITNProject TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by the National Natural Science Foundation of China(Grant No.81503128,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-008,China)supported by National Institute of Health(NS R01-035546,USA)supported by the National Natural Science Foundation of China(Grant No.81400140,China)CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-011,China)supported by European Marie Sklodowska Curie ITN Project TRAIN-TRIBBLES Research and Innovation Network(Grant No.721532,EU)supported by Spanish Ministry of Economy and Competitiveness(MINECO)and Fondo Europeo de desarrollo Regional(FEDER)(Grant No.INNPACTO/IPT-2012-0614-010000,Spain)supported by the National Natural Science Foundation of China(Grant Nos.81400286 and 81530093,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-010,China)supported by the National Natural Science Foundation of China(Grant Nos.81472717 and 81673474,China)Beijing Natural Science Foundation(Grant No.7162133,China)the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-1-007,China)supported by the National Natural Science Foundation of China(Grant No.81703564,China)supported by the National Natural Science Foundation of China(Grant No.81603129,China)
文摘The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.
基金Supported by the First Grade of China Postdoctoral Science Foundation(No.20070410129)the Special Fund by China Postdoctoral Science Foundation(No.200801166)+1 种基金the Major Project of Beijing Municipal Science and Technology Committee (No.H020920010330)the Subject of Science and Technology Plan of Beijng Municipal Science and Technology Committee(No.D08050703020802)
文摘Objective：To study the protective effect of the Mixture of Shengmai Powder and Danshen Decoction（生脉散丹参饮合剂,abbreviated as the Mixture） in the rat model with type 2 diabetic cardiomyopathy （DCM）.Methods：Forty-two SD rats with DCM model,established by the combination of insulin resistance by a high-fat diet with the damage of pancreatic islet p cells by intraperitoneal injection of high dose streptozotocin （50 mg/kg） once,were evaluated in the damage of the myocardium by electrocardiogram at the end of 12 weeks of grouping and intervention administration;the extent of damage in the myocardial subcellular structure was observed by electron microscopy;the content of myocardial collagen in the left cardiac ventricle was quantified by Masson staining test;the myocardial cell apoptosis was determined by TUNEL;the changes in the mRNA expression levels of thrombospodin-1（TSP-1） and tribbles homolog 3（TRB-3） by real-time quantitative PCR,the expression levels of myocardial TSP-1,tumor growth factorβ1（TGF-β1）,TRB-3,and chymase were detected by immunohistochemistry,and the changes in the expression levels of myocardial TSP-1,active-TGF-β1 （A-TGF-β1） and latent-TGF-β1（L-TGF-β1） protein were tested by Western blotting.Results：Compared with the control group,the myocardial tissue was less damaged,and the extent of damage in the myocardial subcellular structure was less;the collagen fiber content and the cell apoptosis were reduced;the expression levels of TSP-1 mRNA and TRB-3 mRNA,the expression levels of myocardial TSP-1,TGF-β1,TRB-3,and chymase,as well as the average expression levels of the myocardial TSP-1,A-TGFβ1,and L-TGF-β1 protein were decreased in the Mixture group.Conclusion：The Mixture of Shengmai Powder and Danshen Decoction could inhibit the process of myocardial fibrosis in the rat myocardium of DCM through multiple pathways and significantly delay the genesis and progress of DCM in hyperglycemic rats.
