为了探究NUPR1基因在奶牛乳房炎中的表达及分布规律,通过构建脂磷壁酸(LTA)诱导奶牛乳腺上皮细胞(MAC-T)体外炎症模型,以奶牛核蛋白1(Nucleus Protein 1,NUPR1)基因为研究对象,利用免疫组织化学技术(IHC)测定NUPR1在患病奶牛乳腺组织中...为了探究NUPR1基因在奶牛乳房炎中的表达及分布规律,通过构建脂磷壁酸(LTA)诱导奶牛乳腺上皮细胞(MAC-T)体外炎症模型,以奶牛核蛋白1(Nucleus Protein 1,NUPR1)基因为研究对象,利用免疫组织化学技术(IHC)测定NUPR1在患病奶牛乳腺组织中的分布情况。通过实时荧光定量PCR(qRT-PCR)及蛋白免疫印迹(WB)检测炎症相关因子、NUPR1基因及其上下游基因在奶牛乳腺炎组织及乳腺上皮细胞炎症模型中的表达规律。qRT-PCR和WB结果显示,IL-1β、IL-6、IL-8和TNF-α在乳腺病理组织及细胞炎症模型中均极显著上调表达(P<0.01),NUPR1在奶牛乳房炎病理乳腺组织及乳腺上皮细胞炎症模型中均显著或极显著上调表达(P<0.05,P<0.01),同时,DNMT1下调表达,KLF4、SESN2和SOCS3基因上调极显著表达(P<0.01)。IHC结果显示,NUPR1主要表达于奶牛乳腺上皮细胞中,并且在奶牛患病乳腺组织中的表达量高于正常组。本研究结果为进一步探究NUPR1基因在乳房炎病理进程中的调控机理提供了试验和理论基础。展开更多
毒品滥用给社会、经济、政治和人们身心健康带来严重危害,已成为许多国家普遍关注的世界性社会问题。甲基苯丙胺(methamphetamine,METH),属于苯丙胺类兴奋剂,俗称“冰毒”。根据我国最新毒品报告显示,METH滥用已成为我国滥用人数最多的...毒品滥用给社会、经济、政治和人们身心健康带来严重危害,已成为许多国家普遍关注的世界性社会问题。甲基苯丙胺(methamphetamine,METH),属于苯丙胺类兴奋剂,俗称“冰毒”。根据我国最新毒品报告显示,METH滥用已成为我国滥用人数最多的毒品。核蛋白1(nuclear protein 1,Nupr1)和内质网应激(endoplasmic reticulum stress,ERS)参与机体多种功能的调节。NLRP3炎性小体是一种复合体,在炎症反应中发挥重要作用。大量研究表明,毒品滥用或在某些疾病发展过程中,可激活Nupr1以及氧化应激和ERS,从而激活NLRP3炎性小体,使IL-1β和IL-18大量释放,从而诱导炎症反应,该过程可诱导细胞炎症性死亡(又称细胞焦亡),从而增加毒品滥用的毒性作用和疾病的发展。Nupr1、ERS和NLRP3炎性小体在甲基苯丙胺诱导神经毒性作用中发挥重要作用,本文主要从Nupr1、ERS和NLRP3炎性小体对甲基苯丙胺毒性作用机制方面进行综述,旨在为进一步研究甲基苯丙胺毒性作用机制提供参考。展开更多
试验旨在研究核蛋白1(nuclear protein 1,Nupr1)mRNA在小鼠早期妊娠子宫中的表达,探讨Nupr1与小鼠胚胎着床的相关性。通过建立小鼠早期妊娠模型、假孕妊娠模型、延迟着床及激活模型、人工蜕膜化模型和激素处理模型,采用原位杂交的方法检...试验旨在研究核蛋白1(nuclear protein 1,Nupr1)mRNA在小鼠早期妊娠子宫中的表达,探讨Nupr1与小鼠胚胎着床的相关性。通过建立小鼠早期妊娠模型、假孕妊娠模型、延迟着床及激活模型、人工蜕膜化模型和激素处理模型,采用原位杂交的方法检测Nupr1mRNA在小鼠各种模型子宫组织中的定位表达情况,并应用实时荧光定量PCR法检测早期妊娠模型和假孕妊娠模型中Nupr1mRNA的相对表达量。结果显示,Nupr1mRNA在小鼠早期妊娠第1~4天子宫的腔上皮和腺上皮表达,第5~8天表达于蜕膜区域;假孕妊娠第1~5天,Nupr1mRNA主要表达于小鼠子宫腔上皮和腺上皮;延迟着床模型中信号表达于在小鼠子宫的腔上皮和腺上皮,与正常妊娠第4天结果相似;延迟激活模型中信号表达于蜕膜区,与早期妊娠第5天表达结果相似;人工蜕膜化模型中信号表达于蜕膜区,而蜕膜对照组中信号表达于腔上皮和腺上皮;17β-雌二醇(oestrogen,E2)处理组信号表达于腔上皮和腺上皮,信号增强,孕酮(progesterone,P4)和E2共同处理表达无明显变化;实时荧光定量PCR结果显示,正常妊娠第2天Nupr1mRNA相对表达量较高,假孕妊娠第2天Nupr1mRNA相对表达量也较高。本研究结果表明,Nupr1mRNA在小鼠子宫中的表达与小鼠早期妊娠过程相关,Nupr1mRNA在腔上皮和腺上皮的表达可能受激素调节,在子宫基质中的表达与蜕膜化及活化胚泡相关。展开更多
核蛋白1 (Nuclear protein 1, NUPR1)是一种位于细胞核内的转录调控因子,可在不同的应激环境和条件下被诱导表达,并参与多种细胞生理过程,如染色质重塑、细胞周期和细胞凋亡。近期研究已经证实,NUPR1可促进多种肿瘤的进展及转移,如非小...核蛋白1 (Nuclear protein 1, NUPR1)是一种位于细胞核内的转录调控因子,可在不同的应激环境和条件下被诱导表达,并参与多种细胞生理过程,如染色质重塑、细胞周期和细胞凋亡。近期研究已经证实,NUPR1可促进多种肿瘤的进展及转移,如非小细胞肺癌、乳腺癌、胰腺癌等。在本综述中,我们旨在讨论NUPR1在恶性肿瘤中的研究进展,为后续NUPR1作为预测肿瘤转移和预后的分子生物标志物指导临床提供新思路。展开更多
Ovarian tumor(OT)is the most lethal form of gynecologic malignancy,with minimal improvements in patient outcomes over the past several decades.Metastasis is the leading cause of ovarian cancer-related deaths,yet the u...Ovarian tumor(OT)is the most lethal form of gynecologic malignancy,with minimal improvements in patient outcomes over the past several decades.Metastasis is the leading cause of ovarian cancer-related deaths,yet the underlying mechanisms remain poorly understood.Psychological stress is known to activate the glucocorticoid receptor(NR3C1),a factor associated with poor prognosis in OT patients.However,the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated.In this study,we demonstrate that chronic restraint stress accelerates epithelialemesenchymal transition(EMT)and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1(NUPR1).Mechanistically,NR3C1 directly regulates the transcription of NUPR1,which in turn increases the expression of snail family transcriptional repressor 2(SNAI2),a key driver of EMT.Clinically,elevated NR3C1 positively correlates with NUPR1 expression in OT patients,and both are positively associated with poorer prognosis.Overall,our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis,suggesting a potential therapeutic target for intervention in OT metastasis.展开更多
Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated gliom...Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated glioma cells and its mechanism in modulating autophagy.We treated TMZ-resistant cells U251-TMZ and T98G-TMZ to normoxia or hypoxia and silenced NUPR1 in hypoxia-treated U251-TMZ and T98G-TMZ cells to assess cell viability,proliferation,apoptosis,LC3-II/LC3-I and p62 expressions,and autophagic flux under different concentrations of TMZ.We found that hypoxia upregulated NUPR1 expression and autophagy while NUPR1 silencing suppressed hypoxia-induced TMZ resistance and autophagy in glioma cells.We also investigated the interaction between NUPR1 and lysine demethylase 3A(KDM3A),as well as the enrichments of KDM3A and H3 lysine 9 dimethylation(H3K9me2)in the transcription factor EB(TFEB)promoter region.Our results suggest that hypoxia-induced NUPR1 promotes TFEB transcription by binding to KDM3A and reducing H3K9me2 levels,thereby augmenting glioma cell autophagy and TMZ resistance.Moreover,the overexpression of KDM3A or TFEB promoted glioma cell autophagy.In a xenograft tumor model,silencing NUPR1 suppressed TMZ resistance in glioma cells in vivo.Overall,our findings highlight a mechanism by which NUPR1 enhances glioma cell autophagy and TMZ resistance via the KDM3A/TFEB axis.展开更多
文摘为了探究NUPR1基因在奶牛乳房炎中的表达及分布规律,通过构建脂磷壁酸(LTA)诱导奶牛乳腺上皮细胞(MAC-T)体外炎症模型,以奶牛核蛋白1(Nucleus Protein 1,NUPR1)基因为研究对象,利用免疫组织化学技术(IHC)测定NUPR1在患病奶牛乳腺组织中的分布情况。通过实时荧光定量PCR(qRT-PCR)及蛋白免疫印迹(WB)检测炎症相关因子、NUPR1基因及其上下游基因在奶牛乳腺炎组织及乳腺上皮细胞炎症模型中的表达规律。qRT-PCR和WB结果显示,IL-1β、IL-6、IL-8和TNF-α在乳腺病理组织及细胞炎症模型中均极显著上调表达(P<0.01),NUPR1在奶牛乳房炎病理乳腺组织及乳腺上皮细胞炎症模型中均显著或极显著上调表达(P<0.05,P<0.01),同时,DNMT1下调表达,KLF4、SESN2和SOCS3基因上调极显著表达(P<0.01)。IHC结果显示,NUPR1主要表达于奶牛乳腺上皮细胞中,并且在奶牛患病乳腺组织中的表达量高于正常组。本研究结果为进一步探究NUPR1基因在乳房炎病理进程中的调控机理提供了试验和理论基础。
文摘毒品滥用给社会、经济、政治和人们身心健康带来严重危害,已成为许多国家普遍关注的世界性社会问题。甲基苯丙胺(methamphetamine,METH),属于苯丙胺类兴奋剂,俗称“冰毒”。根据我国最新毒品报告显示,METH滥用已成为我国滥用人数最多的毒品。核蛋白1(nuclear protein 1,Nupr1)和内质网应激(endoplasmic reticulum stress,ERS)参与机体多种功能的调节。NLRP3炎性小体是一种复合体,在炎症反应中发挥重要作用。大量研究表明,毒品滥用或在某些疾病发展过程中,可激活Nupr1以及氧化应激和ERS,从而激活NLRP3炎性小体,使IL-1β和IL-18大量释放,从而诱导炎症反应,该过程可诱导细胞炎症性死亡(又称细胞焦亡),从而增加毒品滥用的毒性作用和疾病的发展。Nupr1、ERS和NLRP3炎性小体在甲基苯丙胺诱导神经毒性作用中发挥重要作用,本文主要从Nupr1、ERS和NLRP3炎性小体对甲基苯丙胺毒性作用机制方面进行综述,旨在为进一步研究甲基苯丙胺毒性作用机制提供参考。
文摘试验旨在研究核蛋白1(nuclear protein 1,Nupr1)mRNA在小鼠早期妊娠子宫中的表达,探讨Nupr1与小鼠胚胎着床的相关性。通过建立小鼠早期妊娠模型、假孕妊娠模型、延迟着床及激活模型、人工蜕膜化模型和激素处理模型,采用原位杂交的方法检测Nupr1mRNA在小鼠各种模型子宫组织中的定位表达情况,并应用实时荧光定量PCR法检测早期妊娠模型和假孕妊娠模型中Nupr1mRNA的相对表达量。结果显示,Nupr1mRNA在小鼠早期妊娠第1~4天子宫的腔上皮和腺上皮表达,第5~8天表达于蜕膜区域;假孕妊娠第1~5天,Nupr1mRNA主要表达于小鼠子宫腔上皮和腺上皮;延迟着床模型中信号表达于在小鼠子宫的腔上皮和腺上皮,与正常妊娠第4天结果相似;延迟激活模型中信号表达于蜕膜区,与早期妊娠第5天表达结果相似;人工蜕膜化模型中信号表达于蜕膜区,而蜕膜对照组中信号表达于腔上皮和腺上皮;17β-雌二醇(oestrogen,E2)处理组信号表达于腔上皮和腺上皮,信号增强,孕酮(progesterone,P4)和E2共同处理表达无明显变化;实时荧光定量PCR结果显示,正常妊娠第2天Nupr1mRNA相对表达量较高,假孕妊娠第2天Nupr1mRNA相对表达量也较高。本研究结果表明,Nupr1mRNA在小鼠子宫中的表达与小鼠早期妊娠过程相关,Nupr1mRNA在腔上皮和腺上皮的表达可能受激素调节,在子宫基质中的表达与蜕膜化及活化胚泡相关。
文摘核蛋白1 (Nuclear protein 1, NUPR1)是一种位于细胞核内的转录调控因子,可在不同的应激环境和条件下被诱导表达,并参与多种细胞生理过程,如染色质重塑、细胞周期和细胞凋亡。近期研究已经证实,NUPR1可促进多种肿瘤的进展及转移,如非小细胞肺癌、乳腺癌、胰腺癌等。在本综述中,我们旨在讨论NUPR1在恶性肿瘤中的研究进展,为后续NUPR1作为预测肿瘤转移和预后的分子生物标志物指导临床提供新思路。
基金supported,in part,by the National Natural Science Foundation of China(Nos.82374327,81973718,T2341004,and 82321004)Natural Science Foundation of Guangdong Province(Nos.2021A1515011297,2023B1515040016,2019A1515110952and 2022A1515012240,China)+7 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036,China)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2019,China)Guangzhou Basic and Applied Basic Research Foundation(No.2024A04J4020,China)Science and Technology Program of Guangzhou(Nos.202201020483 and 202201010786,China)Foundation of Guangdong Second Provincial General Hospital(No.3DA2021015,China)Innovation Team Project of Guangdong Provincial Department of Education(No.2020KCXTD003,China)GuangdongeHong KongeMacao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine(No.2023LSYS002,China)Guangzhou Key Laboratory of Traditional Chinese Medicine&Disease Susceptibility(No.2024A03J090,China).
文摘Ovarian tumor(OT)is the most lethal form of gynecologic malignancy,with minimal improvements in patient outcomes over the past several decades.Metastasis is the leading cause of ovarian cancer-related deaths,yet the underlying mechanisms remain poorly understood.Psychological stress is known to activate the glucocorticoid receptor(NR3C1),a factor associated with poor prognosis in OT patients.However,the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated.In this study,we demonstrate that chronic restraint stress accelerates epithelialemesenchymal transition(EMT)and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1(NUPR1).Mechanistically,NR3C1 directly regulates the transcription of NUPR1,which in turn increases the expression of snail family transcriptional repressor 2(SNAI2),a key driver of EMT.Clinically,elevated NR3C1 positively correlates with NUPR1 expression in OT patients,and both are positively associated with poorer prognosis.Overall,our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis,suggesting a potential therapeutic target for intervention in OT metastasis.
基金supported by Scientific Research Project of Education Department of Liaoning Province(Grant Number LJKZ0854).
文摘Temozolomide(TMZ)resistance is a major obstacle in glioma treatment.Nuclear protein-1(NUPR1)is a regulator of glioma progression.This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxiatreated glioma cells and its mechanism in modulating autophagy.We treated TMZ-resistant cells U251-TMZ and T98G-TMZ to normoxia or hypoxia and silenced NUPR1 in hypoxia-treated U251-TMZ and T98G-TMZ cells to assess cell viability,proliferation,apoptosis,LC3-II/LC3-I and p62 expressions,and autophagic flux under different concentrations of TMZ.We found that hypoxia upregulated NUPR1 expression and autophagy while NUPR1 silencing suppressed hypoxia-induced TMZ resistance and autophagy in glioma cells.We also investigated the interaction between NUPR1 and lysine demethylase 3A(KDM3A),as well as the enrichments of KDM3A and H3 lysine 9 dimethylation(H3K9me2)in the transcription factor EB(TFEB)promoter region.Our results suggest that hypoxia-induced NUPR1 promotes TFEB transcription by binding to KDM3A and reducing H3K9me2 levels,thereby augmenting glioma cell autophagy and TMZ resistance.Moreover,the overexpression of KDM3A or TFEB promoted glioma cell autophagy.In a xenograft tumor model,silencing NUPR1 suppressed TMZ resistance in glioma cells in vivo.Overall,our findings highlight a mechanism by which NUPR1 enhances glioma cell autophagy and TMZ resistance via the KDM3A/TFEB axis.
