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
目的以RNA干扰抑制血管平滑肌细胞(vascu lar smooth musc le cells,VSMCs)ORC1基因,探讨ORC1基因表达抑制后VSMCs增殖的变化。方法实验设置正常对照组、阴性siRNA组及阳性(ORC1+A、ORC1+B、ORC1+C)siR-NA组。应用W estern b lot检测ORC...目的以RNA干扰抑制血管平滑肌细胞(vascu lar smooth musc le cells,VSMCs)ORC1基因,探讨ORC1基因表达抑制后VSMCs增殖的变化。方法实验设置正常对照组、阴性siRNA组及阳性(ORC1+A、ORC1+B、ORC1+C)siR-NA组。应用W estern b lot检测ORC1基因表达的变化;应用MTT比色试验、3H-TdR掺入试验检测VSMCs增殖的情况。免疫细胞化学染色观察增殖细胞核抗原(proliferating cell nuc lear antigen,PCNA)表达。结果①siRNA转染后,3个阳性siRNA转染组ORC1基因表达水平均降低,尤以第2对阳性siRNA抑制效果最为显著,而空白对照组及阴性对照组间ORC1基因表达水平无显著差异。②siRNA转染使ORC1表达减弱后,VSMCs的MTT吸光度值3、H-TdR掺入量和PCNA表达量均较空白对照组及阴性对照组显著降低。结论RNA干扰介导的ORC1基因沉寂可显著抑制VSMCs增殖。展开更多
目的:研究组蛋白乙酰转移酶结合起始复合物1(histone acetyltransferase binding to ORC1,HBO1)和Geminin在胶质瘤中表达及其与胶质瘤临床病理特征关系。方法:运用免疫组织化学方法检测59例胶质瘤中HBO1和Geminin的表达,分析HBO1和Gemi...目的:研究组蛋白乙酰转移酶结合起始复合物1(histone acetyltransferase binding to ORC1,HBO1)和Geminin在胶质瘤中表达及其与胶质瘤临床病理特征关系。方法:运用免疫组织化学方法检测59例胶质瘤中HBO1和Geminin的表达,分析HBO1和Geminin二者表达的相关性,以及HBO1与临床病理因素间的关系。结果:HBO1、Geminin的总阳性率分别为78.0%、83.1%。HBO1在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为40.0%(6/15)、81.0%(17/21)、100.0%(23/23),并与肿瘤坏死及细胞核分裂像多少有关(P<0.05)。Geminin在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为53.3%(8/15)、85.7%(18/21)、100.0%(23/23),在不同级别胶质瘤中HBO1和Geminin表达差异有统计学意义(P<0.05),表达强度与肿瘤分级呈正相关(r=27.802、32.340,P<0.05)。胶质瘤中HBO1与Geminin表达呈正相关(r=0.692,P<0.05),在胶质瘤中随着Geminin表达增高,HBO1也表达增高。结论:HBO1和Geminin表达与胶质瘤分级相关,联合检测HBO1和Geminin有助于判断胶质瘤恶性程度及预后。展开更多
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.
文摘目的以RNA干扰抑制血管平滑肌细胞(vascu lar smooth musc le cells,VSMCs)ORC1基因,探讨ORC1基因表达抑制后VSMCs增殖的变化。方法实验设置正常对照组、阴性siRNA组及阳性(ORC1+A、ORC1+B、ORC1+C)siR-NA组。应用W estern b lot检测ORC1基因表达的变化;应用MTT比色试验、3H-TdR掺入试验检测VSMCs增殖的情况。免疫细胞化学染色观察增殖细胞核抗原(proliferating cell nuc lear antigen,PCNA)表达。结果①siRNA转染后,3个阳性siRNA转染组ORC1基因表达水平均降低,尤以第2对阳性siRNA抑制效果最为显著,而空白对照组及阴性对照组间ORC1基因表达水平无显著差异。②siRNA转染使ORC1表达减弱后,VSMCs的MTT吸光度值3、H-TdR掺入量和PCNA表达量均较空白对照组及阴性对照组显著降低。结论RNA干扰介导的ORC1基因沉寂可显著抑制VSMCs增殖。
文摘目的:研究组蛋白乙酰转移酶结合起始复合物1(histone acetyltransferase binding to ORC1,HBO1)和Geminin在胶质瘤中表达及其与胶质瘤临床病理特征关系。方法:运用免疫组织化学方法检测59例胶质瘤中HBO1和Geminin的表达,分析HBO1和Geminin二者表达的相关性,以及HBO1与临床病理因素间的关系。结果:HBO1、Geminin的总阳性率分别为78.0%、83.1%。HBO1在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为40.0%(6/15)、81.0%(17/21)、100.0%(23/23),并与肿瘤坏死及细胞核分裂像多少有关(P<0.05)。Geminin在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性率分别为53.3%(8/15)、85.7%(18/21)、100.0%(23/23),在不同级别胶质瘤中HBO1和Geminin表达差异有统计学意义(P<0.05),表达强度与肿瘤分级呈正相关(r=27.802、32.340,P<0.05)。胶质瘤中HBO1与Geminin表达呈正相关(r=0.692,P<0.05),在胶质瘤中随着Geminin表达增高,HBO1也表达增高。结论:HBO1和Geminin表达与胶质瘤分级相关,联合检测HBO1和Geminin有助于判断胶质瘤恶性程度及预后。
