目的:在小鼠骨性关节炎(osteoarthritis,OA)模型中观察沉默信息转录调控因子1(sirtuin type 1,SIRT1)信号通路对软骨细胞代谢的影响以及线粒体抗氧化应激能力的改变,探讨SIRT1信号通路及薯蓣皂苷元(diosgenin,Dgn)在OA过程中的作用。方...目的:在小鼠骨性关节炎(osteoarthritis,OA)模型中观察沉默信息转录调控因子1(sirtuin type 1,SIRT1)信号通路对软骨细胞代谢的影响以及线粒体抗氧化应激能力的改变,探讨SIRT1信号通路及薯蓣皂苷元(diosgenin,Dgn)在OA过程中的作用。方法:选择10只C57BL/6小鼠(13.5~18.0 g)建立OA模型,4周后取材,培养软骨细胞并随机分为4组:OA组、Dgn+OA组、Dgn+Sirtinol(SIRT1通路阻断剂)+OA组及Sirtinol+OA组。运用Western印迹法检测各组细胞SIRT1,乙酰化-调节叉头转录因子1(acetylation-regulated transcription factor 1,Ac-FOXO1)和Bax蛋白的表达,同时检测各组线粒体氧化应激指标琥珀酸脱氢酶(succinate dehydrogenase,SDH)、细胞色素C氧化酶(cytochrome C oxidase,COX)、超氧化物歧化酶(superoxide dismutase,SOD)水平的改变。结果:与OA组比较,Dgn明显增高SIRT1表达水平(P<0.05),降低Ac-FOXO1和Bax蛋白表达水平(P<0.05),SDH和COX蛋白表达水平及SOD含量均升高(P<0.05);而与OA+Dgn组相比,Sirtinol明显降低SIRT1的表达,增高Ac-FOXO1蛋白和Bax蛋白表达水平,降低SDH和COX蛋白表达水平及SOD含量(P<0.05)。结论:SIRT1信号通路和OA中软骨细胞变化密切相关,Dgn通过激活SIRT1通路,有效减轻OA病理过程中软骨细胞的线粒体氧化应激损伤,从而发挥抗OA中软骨细胞保护作用。展开更多
目的探讨沉默信息调节因子1(Sirtuin Type 1,SIRTl)在人乳腺癌组织、癌旁正常组织中的表达及临床意义。方法通过免疫组织化学法检测107例人乳腺癌组织及相匹配的44例癌旁正常组织中的SIRTl表达情况,结合临床病理资料进行统计学分析。结...目的探讨沉默信息调节因子1(Sirtuin Type 1,SIRTl)在人乳腺癌组织、癌旁正常组织中的表达及临床意义。方法通过免疫组织化学法检测107例人乳腺癌组织及相匹配的44例癌旁正常组织中的SIRTl表达情况,结合临床病理资料进行统计学分析。结果 SIRTl蛋白在人乳腺癌组织中呈现高表达69.2%(74/107),癌旁组织中低表达或缺失9.1%(4/44),二者差异有统计学意义(P<0.01);SIRTl在人乳腺癌组织中表达与组织学分级、淋巴结转移相关,组织学分级越高、淋巴结转移越多,其阳性表达率越高(P<0.05);SIRTl表达与PR、Ki-67表达呈正相关(P<0.01)。结论 SIRTl在人乳腺癌组织中呈现高表达,SIRT1在乳腺癌中与组织学分级、淋巴结转移有关,且与PR、Ki-67表达呈正相关。展开更多
Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
文摘目的探讨沉默信息调节因子1(Sirtuin Type 1,SIRTl)在人乳腺癌组织、癌旁正常组织中的表达及临床意义。方法通过免疫组织化学法检测107例人乳腺癌组织及相匹配的44例癌旁正常组织中的SIRTl表达情况,结合临床病理资料进行统计学分析。结果 SIRTl蛋白在人乳腺癌组织中呈现高表达69.2%(74/107),癌旁组织中低表达或缺失9.1%(4/44),二者差异有统计学意义(P<0.01);SIRTl在人乳腺癌组织中表达与组织学分级、淋巴结转移相关,组织学分级越高、淋巴结转移越多,其阳性表达率越高(P<0.05);SIRTl表达与PR、Ki-67表达呈正相关(P<0.01)。结论 SIRTl在人乳腺癌组织中呈现高表达,SIRT1在乳腺癌中与组织学分级、淋巴结转移有关,且与PR、Ki-67表达呈正相关。
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
