Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are unclear.Therapeutic treatment of cancer is suboptimal in many cases,with no accurate inde...Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are unclear.Therapeutic treatment of cancer is suboptimal in many cases,with no accurate index by which to evaluate the success of treatment or patient prognosis.In this study,we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia(AML)cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by RNA-seq.We found nuclear phospho-eIF4E,an exporter of oncogenic mRNAs,to be abundant in AML.Further,nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to chemotherapy.The results demonstrate“massive clustering and export of oncogenic mRNAs to the translation machinery”by highly abundant RNA-nuclear phospho-eIF4E bodies.This is an efficient mechanism that may drive the proliferation of cancer cells.Herein,nuclear phospho-eIF4E bodies were identified as potential markers of AML,which may be useful for prognosis and as targets for cancer therapy.展开更多
目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带...目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带状态、tau PET及高分辨结构MRI数据;利用随机森林法筛选tau PET诊断MCI的重要脑区,比较tau PET鉴别携带/未携带APOEε4基因MCI与HC的效能。结果利用tau PET诊断MCI的重要脑区依次为杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回。基于上述7个脑区ROI构建的tau PET标准摄取值比值(SUVR)模型鉴别携带APOEε4基因MCI与HC的准确率及曲线下面积(AUC)分别为86.68%及0.784,高于其鉴别MCI与HC、未携带APOEε4基因MCI与HC(准确率分别为70.57%及75.05%,AUC分别为0.711及0.609)。结论基于杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回构建的^(18)F-flortaucipir tau PET SUVR模型可用于诊断MCI;联合APOEε4基因可进一步提高其诊断效能。展开更多
目的 探讨利拉鲁肽调控核因子E2相关因子2(Nrf2)/谷胱甘肽过氧化物酶4(GPX4)铁死亡信号对DKD大鼠的保护作用。方法 12只雄性SD大鼠随机分为正常对照(NC)组、DKD组和利拉鲁肽治疗(Lir)组,每组4只。检测各组24 h UAlb、TC、TG、LDL-C、血...目的 探讨利拉鲁肽调控核因子E2相关因子2(Nrf2)/谷胱甘肽过氧化物酶4(GPX4)铁死亡信号对DKD大鼠的保护作用。方法 12只雄性SD大鼠随机分为正常对照(NC)组、DKD组和利拉鲁肽治疗(Lir)组,每组4只。检测各组24 h UAlb、TC、TG、LDL-C、血肌酐(Scr)、BUN、亚铁离子(Fe^(2+))、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA),采用HE、PAS、PASM?Masson染色观察肾脏病理学变化,免疫荧光检测肾组织中活性氧簇(ROS)定位及表达,Western blot法检测Nrf2和GPX4蛋白表达。结果 与NC组比较,DKD组24 h UAlb、Scr、BUN、TC、TG、LDL?C、MDA、ROS、Fe^(2+)升高(P<0.05或P<0.01),GSH-Px及Nrf2、GPX4蛋白表达降低(P<0.01)。与DKD组比较,Lir组24 h UAlb、BUN、TC、TG、LDL-C、MDA、ROS、Fe^(2+)降低(P<0.05或P<0.01),GSH-Px及Nrf2、GPX4蛋白表达升高(P<0.01)。结论 利拉鲁肽可能通过上调Nrf2/GPX4信号通路,抑制铁死亡,发挥DKD保护作用。展开更多
基金supported in part by the National Natural Science Foundation of China(Grant No.81600129)the Science and Technology Project of Hangzhou(Grant No.2016Z01)+1 种基金the Science and Technology Project of Hangzhou(Grant No.2017A11)Natural Science Foundation of Zhejiang Province(Grant No.LY21H080001).
文摘Uncontrolled proliferation is a hallmark of cancer cells,yet the molecular mechanisms that contribute to this proliferation are unclear.Therapeutic treatment of cancer is suboptimal in many cases,with no accurate index by which to evaluate the success of treatment or patient prognosis.In this study,we explored the protein levels of nuclear phospho-eIF4E in acute myeloid leukemia(AML)cell lines and primary leukemia samples by Western blot and immunofluorescence and as well analyzed transcriptomes by RNA-seq.We found nuclear phospho-eIF4E,an exporter of oncogenic mRNAs,to be abundant in AML.Further,nuclear phospho-eIF4E abundance was significantly associated with tumor burden as well as the response of AML patients to chemotherapy.The results demonstrate“massive clustering and export of oncogenic mRNAs to the translation machinery”by highly abundant RNA-nuclear phospho-eIF4E bodies.This is an efficient mechanism that may drive the proliferation of cancer cells.Herein,nuclear phospho-eIF4E bodies were identified as potential markers of AML,which may be useful for prognosis and as targets for cancer therapy.
文摘目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带状态、tau PET及高分辨结构MRI数据;利用随机森林法筛选tau PET诊断MCI的重要脑区,比较tau PET鉴别携带/未携带APOEε4基因MCI与HC的效能。结果利用tau PET诊断MCI的重要脑区依次为杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回。基于上述7个脑区ROI构建的tau PET标准摄取值比值(SUVR)模型鉴别携带APOEε4基因MCI与HC的准确率及曲线下面积(AUC)分别为86.68%及0.784,高于其鉴别MCI与HC、未携带APOEε4基因MCI与HC(准确率分别为70.57%及75.05%,AUC分别为0.711及0.609)。结论基于杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回构建的^(18)F-flortaucipir tau PET SUVR模型可用于诊断MCI;联合APOEε4基因可进一步提高其诊断效能。
文摘目的 探讨利拉鲁肽调控核因子E2相关因子2(Nrf2)/谷胱甘肽过氧化物酶4(GPX4)铁死亡信号对DKD大鼠的保护作用。方法 12只雄性SD大鼠随机分为正常对照(NC)组、DKD组和利拉鲁肽治疗(Lir)组,每组4只。检测各组24 h UAlb、TC、TG、LDL-C、血肌酐(Scr)、BUN、亚铁离子(Fe^(2+))、谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA),采用HE、PAS、PASM?Masson染色观察肾脏病理学变化,免疫荧光检测肾组织中活性氧簇(ROS)定位及表达,Western blot法检测Nrf2和GPX4蛋白表达。结果 与NC组比较,DKD组24 h UAlb、Scr、BUN、TC、TG、LDL?C、MDA、ROS、Fe^(2+)升高(P<0.05或P<0.01),GSH-Px及Nrf2、GPX4蛋白表达降低(P<0.01)。与DKD组比较,Lir组24 h UAlb、BUN、TC、TG、LDL-C、MDA、ROS、Fe^(2+)降低(P<0.05或P<0.01),GSH-Px及Nrf2、GPX4蛋白表达升高(P<0.01)。结论 利拉鲁肽可能通过上调Nrf2/GPX4信号通路,抑制铁死亡,发挥DKD保护作用。
