We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repet...We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.展开更多
Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the stu...Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.展开更多
目的探讨微小RNA(miR)-483-3p在原发性高血压患者血清中的水平及诊断价值。方法选取2021年1月至2023年3月于三亚中心医院心内科就诊并确诊为原发性高血压的患者180例作为研究组,选取同期来我院体检且与研究组一般资料匹配的健康志愿者16...目的探讨微小RNA(miR)-483-3p在原发性高血压患者血清中的水平及诊断价值。方法选取2021年1月至2023年3月于三亚中心医院心内科就诊并确诊为原发性高血压的患者180例作为研究组,选取同期来我院体检且与研究组一般资料匹配的健康志愿者160例作为对照组。实时荧光定量聚合酶链反应检测2组血清miR-483-3p水平。结果与对照组比较,研究组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、收缩压、舒张压水平升高(P<0.01)。研究组血清miR-483-3p水平高于对照组(2.15±0.57 vs 1.00±0.05,P<0.01)。研究组中高血压1级、2级、3级患者血清miR-483-3p水平呈明显升高趋势(1.44±0.45 vs 1.79±0.58 vs 3.35±0.64,P<0.05)。相关性分析显示,研究组血清miR-483-3p水平与高血压分级呈正相关(r=0.745,P=0.000);研究组血清miR-483-3p水平与TC、TG、LDL-C、收缩压、舒张压水平均呈正相关(P<0.01)。miR-483-3p、TC、LDL-C、收缩压、舒张压是原发性高血压的独立影响因素(P<0.05,P<0.01)。血清miR-483-3p水平预测原发性高血压的曲线下面积为0.923(95%CI:0.890~0.949)。结论miR-483-3p在原发性高血压患者血清中的水平随病情严重程度的加重呈上升趋势,对原发性高血压有较高的诊断价值。展开更多
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBSS00047(to PL)the National Natural Science Foundation of China,Nos.82072166(to PL),82071394(to XG)+4 种基金Science and Technology Planning Project of Tianjin,No.20YFZCSY00030(to PL)Science and Technology Project of Tianjin Municipal Health Commission,No.TJWJ2021QN005(to XG)Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-006ATianjin Municipal Education Commission Scientific Research Program Project,No.2020KJ164(to JZ)China Postdoctoral Science Foundation,No.2022M712392(to ZY).
文摘We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.
文摘Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.
文摘目的探讨微小RNA(miR)-483-3p在原发性高血压患者血清中的水平及诊断价值。方法选取2021年1月至2023年3月于三亚中心医院心内科就诊并确诊为原发性高血压的患者180例作为研究组,选取同期来我院体检且与研究组一般资料匹配的健康志愿者160例作为对照组。实时荧光定量聚合酶链反应检测2组血清miR-483-3p水平。结果与对照组比较,研究组总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、收缩压、舒张压水平升高(P<0.01)。研究组血清miR-483-3p水平高于对照组(2.15±0.57 vs 1.00±0.05,P<0.01)。研究组中高血压1级、2级、3级患者血清miR-483-3p水平呈明显升高趋势(1.44±0.45 vs 1.79±0.58 vs 3.35±0.64,P<0.05)。相关性分析显示,研究组血清miR-483-3p水平与高血压分级呈正相关(r=0.745,P=0.000);研究组血清miR-483-3p水平与TC、TG、LDL-C、收缩压、舒张压水平均呈正相关(P<0.01)。miR-483-3p、TC、LDL-C、收缩压、舒张压是原发性高血压的独立影响因素(P<0.05,P<0.01)。血清miR-483-3p水平预测原发性高血压的曲线下面积为0.923(95%CI:0.890~0.949)。结论miR-483-3p在原发性高血压患者血清中的水平随病情严重程度的加重呈上升趋势,对原发性高血压有较高的诊断价值。
