Nr4a3(nuclear receptor subfamily 4 group a member 3)属于核受体亚家族成员,参与细胞增殖、细胞迁移和细胞凋亡的调控。据报道,Nr4a3在多种肿瘤组织中表达下调。为探索Nr4a3在乳腺癌发生、发展中的作用,本文利用公共数据库分析NR4A3...Nr4a3(nuclear receptor subfamily 4 group a member 3)属于核受体亚家族成员,参与细胞增殖、细胞迁移和细胞凋亡的调控。据报道,Nr4a3在多种肿瘤组织中表达下调。为探索Nr4a3在乳腺癌发生、发展中的作用,本文利用公共数据库分析NR4A3在乳腺癌组织中的表达以及与乳腺癌患者总生存率的关系。在4T1细胞系上敲除Nr4a3基因,通过流式细胞术等检测细胞凋亡、细胞周期;CCK-8与集落形成实验检测细胞活力;细胞划痕与侵袭检测细胞迁移与侵袭能力;通过q-PCR检测细胞周期和凋亡基因的表达水平。结果表明:Nr4a3在乳腺癌组织中表达水平显著下调;与乳腺癌患者的总生存率呈正相关关系;Nr4a3敲除后,细胞增殖增强,细胞凋亡减少及细胞迁移能力和侵袭能力增强。本研究揭示了Nr4a3在乳腺癌细胞增殖、凋亡、迁移和侵袭的潜在作用,可能成为乳腺癌潜在的治疗靶点。展开更多
Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and prese...Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and preservation of the heart,especially when a long cold ischemic time is required.Here,we propose a novel donor heart procurement and preservation method—crystalloid cardioplegia(CC)+UW involving an initial cardioplegic flush with crystalloid cardioplegia followed by preservation in UW solution.Our results demonstrated that compared with using UW solution alone,the CC+UW method could effectively reduce metabolite consumption and suppress the activation of the NFκB signaling pathway in a pig model.NR4A3 was found to be upregulated in CC+UW,which could suppress the expression of DUSP2and thereby decrease p65 phosphorylation.In addition,the CC+UW method increased intraventricular pressure and improved electrical conduction and rhythm in Langendorff-perfused rat hearts.Mediumterm survival data for heart transplant patients also confirmed the benefits of this method.In conclusion,our study identifies the CC+UW method as an effective strategy for donor heart procurement and preservation,showing that it can reduce energy consumption and decrease inflammation;therefore,this method is a promising technique for expanding the criteria for heart transplantation and alleviating the shortage of donor hearts.展开更多
文摘Nr4a3(nuclear receptor subfamily 4 group a member 3)属于核受体亚家族成员,参与细胞增殖、细胞迁移和细胞凋亡的调控。据报道,Nr4a3在多种肿瘤组织中表达下调。为探索Nr4a3在乳腺癌发生、发展中的作用,本文利用公共数据库分析NR4A3在乳腺癌组织中的表达以及与乳腺癌患者总生存率的关系。在4T1细胞系上敲除Nr4a3基因,通过流式细胞术等检测细胞凋亡、细胞周期;CCK-8与集落形成实验检测细胞活力;细胞划痕与侵袭检测细胞迁移与侵袭能力;通过q-PCR检测细胞周期和凋亡基因的表达水平。结果表明:Nr4a3在乳腺癌组织中表达水平显著下调;与乳腺癌患者的总生存率呈正相关关系;Nr4a3敲除后,细胞增殖增强,细胞凋亡减少及细胞迁移能力和侵袭能力增强。本研究揭示了Nr4a3在乳腺癌细胞增殖、凋亡、迁移和侵袭的潜在作用,可能成为乳腺癌潜在的治疗靶点。
基金supported by the National Key Research and Development Program(2021YFA1101900)Key Research Development Program of Hubei Province(2020BCA061)+1 种基金the National Natural Science Foundation of China(82200410,82470423,82204659,and 82300413)Hubei Provincial Natural Science Foundation Projects(JCZRYB202500142)。
文摘Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and preservation of the heart,especially when a long cold ischemic time is required.Here,we propose a novel donor heart procurement and preservation method—crystalloid cardioplegia(CC)+UW involving an initial cardioplegic flush with crystalloid cardioplegia followed by preservation in UW solution.Our results demonstrated that compared with using UW solution alone,the CC+UW method could effectively reduce metabolite consumption and suppress the activation of the NFκB signaling pathway in a pig model.NR4A3 was found to be upregulated in CC+UW,which could suppress the expression of DUSP2and thereby decrease p65 phosphorylation.In addition,the CC+UW method increased intraventricular pressure and improved electrical conduction and rhythm in Langendorff-perfused rat hearts.Mediumterm survival data for heart transplant patients also confirmed the benefits of this method.In conclusion,our study identifies the CC+UW method as an effective strategy for donor heart procurement and preservation,showing that it can reduce energy consumption and decrease inflammation;therefore,this method is a promising technique for expanding the criteria for heart transplantation and alleviating the shortage of donor hearts.
