BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
目的探讨RAB22A在乳腺癌组织中的表达及临床意义。方法采用实时荧光定量PCR检测60例乳腺癌及其相应癌旁组织中RAB22A m RNA的表达,分析其与乳腺癌患者临床病理特征的关系。结果 RAB22A m RNA在乳腺癌组织中的表达高于癌旁组织(4.9±...目的探讨RAB22A在乳腺癌组织中的表达及临床意义。方法采用实时荧光定量PCR检测60例乳腺癌及其相应癌旁组织中RAB22A m RNA的表达,分析其与乳腺癌患者临床病理特征的关系。结果 RAB22A m RNA在乳腺癌组织中的表达高于癌旁组织(4.9±1.1 vs 1.1±0.3,P<0.01)。不同年龄、肿瘤大小以及不同ER、PR、HER-2表达状况乳腺癌患者中RAB22A m RNA的表达差异无统计学意义(P>0.05),但不同淋巴结转移数患者RAB22A m RNA表达差异有统计学意义(P<0.05),高表达RAB22A患者的总生存期较低表达患者差(P<0.05);多因素Cox比例风险回归模型分析结果显示RAB22A和淋巴结转移数是影响预后的独立因素(P<0.05)。结论 RAB22A在乳腺癌组织中表达升高,可能与乳腺癌转移和不良预后有关。展开更多
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
文摘目的探讨RAB22A在乳腺癌组织中的表达及临床意义。方法采用实时荧光定量PCR检测60例乳腺癌及其相应癌旁组织中RAB22A m RNA的表达,分析其与乳腺癌患者临床病理特征的关系。结果 RAB22A m RNA在乳腺癌组织中的表达高于癌旁组织(4.9±1.1 vs 1.1±0.3,P<0.01)。不同年龄、肿瘤大小以及不同ER、PR、HER-2表达状况乳腺癌患者中RAB22A m RNA的表达差异无统计学意义(P>0.05),但不同淋巴结转移数患者RAB22A m RNA表达差异有统计学意义(P<0.05),高表达RAB22A患者的总生存期较低表达患者差(P<0.05);多因素Cox比例风险回归模型分析结果显示RAB22A和淋巴结转移数是影响预后的独立因素(P<0.05)。结论 RAB22A在乳腺癌组织中表达升高,可能与乳腺癌转移和不良预后有关。
文摘目的:探讨miR-302通过靶向调控RAB22A影响膀胱癌进展的分子机制。方法:采用RT-qPCR检测miR-302在HTB1和RT112膀胱癌细胞系和膀胱内皮细胞系HBdNEC中的表达;以miRNA-NC、miR-302 mimic、miR-302 inhibitor转染细胞,并分为以下几组:NC+control si RNA、miR-302 inhibitor+control si RNA、miR-302 inhibitor+RAB22A si RNA、NC+vector、miR-302 mimic+vector或miR-302 mimic+RAB22A,再通过MTT实验分析膀胱癌细胞的增殖情况,细胞侵袭实验检测细胞侵袭情况,双荧光素酶报告载体检测分析miR-302靶基因,Western blot检测RAB22A在膀胱癌细胞中的表达。结果:HTB1和RT112细胞中miR-302的表达明显低于HBdNEC细胞(P<0.05)。miR-302高表达抑制膀胱癌细胞的增殖和侵袭;miR-302低表达时,膀胱癌细胞的增殖和侵袭能力上升。生物信息学和双荧光素酶报告结果显示RAB22A为miR-302的靶基因。miR-302过表达后,细胞荧光素酶活性显著下降(P<0.05),RAB22A表达下调(P<0.05);miR-302表达沉默后,细胞荧光素酶活性显著上升(P<0.05),RAB22A表达上调(P<0.01)。拯救实验显示RAB22A表达沉默可逆转miR-302表达沉默时对膀胱癌细胞增殖和侵袭能力上调的影响;而RAB22A过表达可逆转miR-302过表达对膀胱癌细胞增殖和侵袭的抑制。结论:miR-302可通过抑制靶基因RAB22A的表达,抑制膀胱癌细胞的增殖及侵袭。
