目的探讨G蛋白信号传导调节蛋白6(regulator of G protein signaling 6,RGS6)表达与肝细胞癌(hepatocellular carcinoma,HCC)预后的关系。方法收集HCC肿瘤组织样本100例,通过免疫组织化学检测RGS6在肿瘤组织中的表达情况,采用Kaplan-Me...目的探讨G蛋白信号传导调节蛋白6(regulator of G protein signaling 6,RGS6)表达与肝细胞癌(hepatocellular carcinoma,HCC)预后的关系。方法收集HCC肿瘤组织样本100例,通过免疫组织化学检测RGS6在肿瘤组织中的表达情况,采用Kaplan-Meier生存法和Cox回归模型分析RGS6表达对HCC预后的影响。结果肿瘤组织中RGS6表达减少与更高肿瘤分级、微血管侵犯、肿瘤生长、Ki67高分值等病理特征密切相关(P<0.05);Kaplan-Meier生存曲线分析结果显示肿瘤组织中RGS6表达减少的患者具有更低的生存率(P=0.027),多因素Cox回归分析均显示具有RGS6表达减少的患者死亡风险增加,具体风险值(HR)为157.747(95%CI=5.769~4313.674,P=0.003)。结论RGS6表达是一个影响HCC预后的独立指标,RGS6表达影响HCC预后的可能机制与其影响肿瘤分化、生长、血管浸润等相关。展开更多
Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rode...Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.展开更多
文摘目的探讨G蛋白信号传导调节蛋白6(regulator of G protein signaling 6,RGS6)表达与肝细胞癌(hepatocellular carcinoma,HCC)预后的关系。方法收集HCC肿瘤组织样本100例,通过免疫组织化学检测RGS6在肿瘤组织中的表达情况,采用Kaplan-Meier生存法和Cox回归模型分析RGS6表达对HCC预后的影响。结果肿瘤组织中RGS6表达减少与更高肿瘤分级、微血管侵犯、肿瘤生长、Ki67高分值等病理特征密切相关(P<0.05);Kaplan-Meier生存曲线分析结果显示肿瘤组织中RGS6表达减少的患者具有更低的生存率(P=0.027),多因素Cox回归分析均显示具有RGS6表达减少的患者死亡风险增加,具体风险值(HR)为157.747(95%CI=5.769~4313.674,P=0.003)。结论RGS6表达是一个影响HCC预后的独立指标,RGS6表达影响HCC预后的可能机制与其影响肿瘤分化、生长、血管浸润等相关。
基金supported by the National Institutes of Health,Nos.AA025919,AA025919-03S1,and AA025919-05S1(all to RAF).
文摘Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.
