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
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:探讨基于微小核糖核酸(micrornas,miR)-221-3p、miR-155-5p及英国胸科协会改良肺炎(confusion,uremia,respiratory,BP,age 65years,CURB-65)评分构建的Nomogram预测模型对重症肺炎(severe pneumonia,SP)预后不良的预测价值。方法:前瞻性选取2021年1月至2024年6月宜春市人民医院收治的439例SP患者,按7:3比例随机分为建模组(n=307)与验证组(n=132)。治疗前检测患者血清miR-221-3p、miR-155-5p水平,并使用CURB-65得分进行评估。观察患者住院28 d内预后情况,根据28 d内预后情况将SP患者分为死亡组与存活组。采用Lasso回归分析SP患者预后不好的影响因素,多元素Logistic回归分析SP预后不良的危险因素。构建SP患者预后不良Nomogram预测模型,并采用受试者工作特征(receiver operating characteristic,ROC)曲线评估Nomogram模型对SP预后不良的预测效能。结果:建模组、验证组死亡率分别为29.32%(90/307)、28.79%(38/132),两组死亡率以及临床资料比较无统计学差异(P>0.05)。建模、验证人群中死亡组的年龄、肺部基础疾病比例、肺炎严重指数(pneumonia severity index,PSI)评分、急性生理学和慢性健康状况评分系统Ⅱ(Acute Physiology and Chronic Health EvaluationⅡ,APACHEⅡ)评分、CURB-65评分、血清miR-221-3p、miR-155-5p、C反应蛋白(C-reactive protein,CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、降钙素原(procalcitonin,PCT)指标均高于存活组(P<0.05)。Logistic多因素回归分析显示高龄、高APACHEⅡ评分、miR-221-3p高表达、miR-155-5p高表达、高CURB-65评分是SP预后不良的危险因素(P<0.05)。构建的SP预后不良Nomogram预测模型对SP预后不良的曲线下面积(area under the curve,AUC)达0.824,具有良好的预测效能。结论:miR-221-3p高表达、miR-155-5p高表达、高CURB-65评分、高龄、高APACHEⅡ评分是SP患者预后不良的危险因素,基于上述因素构建的Nomogram预测模型对SP预后不良的预测价值较高。
