Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low...Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
目的探讨外周血miR-141、miR-451a与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者化疗应答的预测价值。方法选取2021年6月至2023年4月我院92例DLBCL患者作为DLBCL组,根据化疗效果分为化疗无效亚组(n=29)与化疗有效亚组(...目的探讨外周血miR-141、miR-451a与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者化疗应答的预测价值。方法选取2021年6月至2023年4月我院92例DLBCL患者作为DLBCL组,根据化疗效果分为化疗无效亚组(n=29)与化疗有效亚组(n=63)。随机选取同期92例入院体检健康者为对照组,采用实时荧光定量聚合酶链反应测定miR-141、miR-451a相对表达量。比较DLBCL组与健康对照组外周血miR-141、miR-451a表达,以logistic回归模型分析筛选DLBCL患者化疗应答影响因素,相关性分析DLBCL患者外周血miR-141、miR-451a与国际预后指数(international prognositic index,IPI)评分、Ann Arbor分期间相关性,受试者工作特征(receiver operating characteristic,ROC)曲线评价DLBCL患者miR-141、miR-451a单项检测及联合检测预测化疗应答的价值。结果DLBCL患者外周血miR-141、miR-451a表达均低于健康对照组(P<0.05);logistic回归分析结果显示Ann Arbor分期、IPI评分均为DLBCL患者化疗应答独立危险因素,外周血miR-141、miR-451a均为DLBCL患者化疗应答性独立保护因素(P<0.05);DLBCL患者外周血miR-141、miR-451a与IPI评分、Ann Arbor分期均具有显著负相关关系(P<0.05);外周血miR-141、miR-451a单独预测DLBCL患者化疗应答的曲线下面积(area under the curve,AUC)值分别为0.770、0.794,二者联合预测AUC值高达0.929,明显高于miR-141、miR-451a单独预测,此时灵敏度、特异度分别为86.21%、85.71%。结论DCBCL患者血清miR-141、miR-451a表达下调,且与应答有关,检测二者水平,可预测DCBCL患者化疗应答,为临床工作提供参考。展开更多
基金supported by China International Medical Foundation(Z-2019-42-1908-4)Natural Science Basic Research Program of Shaanxi Province(2019JM-440).
文摘Objective:To investigate the antifibrotic effects of curcumin in a transverse aortic constriction(TAC)mouse model and elucidate its molecular mechanisms.Methods:Male C57BL/6 mice underwent TAC and received vehicle,low-dose curcumin(50 mg/kg),high-dose curcumin(200 mg/kg),high-dose curcumin plus a scrambled control antagomir,or high-dose curcumin plus anti-miR-29b treatments.Cardiac function was assessed by echocardiography.Fibrosis was evaluated by histology,collagen volume fraction,and hydroxyproline content.Expression of miR-29b,HDAC4,and fibrosis-related markers(Col1a1,Col3a1,TGF-β1)was measured by quantitative RT-PCR and Western blotting assays.Myocardial procollagen type I carboxy-terminal propeptide was determined by ELISA,and HDAC4-specific enzymatic activity was assayed using a fluorogenic kit.Results:Curcumin improved cardiac function,reduced fibrosis,restored miR-29b expression,and suppressed HDAC4 expression and activity in a dose-dependent manner.Furthermore,curcumin decreased myocardial procollagen type I carboxy-terminal propeptide levels,confirming reduced collagen synthesis.Anti-miR-29b administration partially abrogated the antifibrotic and cardioprotective effects of curcumin.Conclusions:Curcumin attenuates pressure overload-induced cardiac fibrosis and dysfunction in a TAC mouse model via modulation of the miR-29b/HDAC4 axis and suppression of collagen synthesis.
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
文摘目的探讨外周血miR-141、miR-451a与弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者化疗应答的预测价值。方法选取2021年6月至2023年4月我院92例DLBCL患者作为DLBCL组,根据化疗效果分为化疗无效亚组(n=29)与化疗有效亚组(n=63)。随机选取同期92例入院体检健康者为对照组,采用实时荧光定量聚合酶链反应测定miR-141、miR-451a相对表达量。比较DLBCL组与健康对照组外周血miR-141、miR-451a表达,以logistic回归模型分析筛选DLBCL患者化疗应答影响因素,相关性分析DLBCL患者外周血miR-141、miR-451a与国际预后指数(international prognositic index,IPI)评分、Ann Arbor分期间相关性,受试者工作特征(receiver operating characteristic,ROC)曲线评价DLBCL患者miR-141、miR-451a单项检测及联合检测预测化疗应答的价值。结果DLBCL患者外周血miR-141、miR-451a表达均低于健康对照组(P<0.05);logistic回归分析结果显示Ann Arbor分期、IPI评分均为DLBCL患者化疗应答独立危险因素,外周血miR-141、miR-451a均为DLBCL患者化疗应答性独立保护因素(P<0.05);DLBCL患者外周血miR-141、miR-451a与IPI评分、Ann Arbor分期均具有显著负相关关系(P<0.05);外周血miR-141、miR-451a单独预测DLBCL患者化疗应答的曲线下面积(area under the curve,AUC)值分别为0.770、0.794,二者联合预测AUC值高达0.929,明显高于miR-141、miR-451a单独预测,此时灵敏度、特异度分别为86.21%、85.71%。结论DCBCL患者血清miR-141、miR-451a表达下调,且与应答有关,检测二者水平,可预测DCBCL患者化疗应答,为临床工作提供参考。
