Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan...Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.展开更多
目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数...目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数及近期疗效的关系。结果食管癌患者血清中miR-451的表达水平明显高于健康对照者(P<0.05),miR-451的ROC曲线下面积(area under the curve,AUC)值取0.911(95%CI=0.844~0.977)时,对食管癌诊断的灵敏度和特异度分别为88%和85%。miR-451的表达水平与食管癌患者的临床分期和淋巴结转移有关。食管癌患者放疗后miR-451表达水平下降(P<0.05),且miR-451的表达水平动态变化与食管癌治疗疗效一致,有效患者miR-451表达水平下降明显高于无效患者(P<0.05)。结论血清miR-451可能对食管癌的早期诊断及非手术治疗疗效的判断有一定的参考价值。展开更多
目的探讨microRNA-451(miR-451)在弥漫性大B细胞淋巴瘤(diffuse large B lymphoma,DLBCL)患者血浆中的表达水平及其临床意义。方法利用逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RTPCR)方法检测27例DLBCL患...目的探讨microRNA-451(miR-451)在弥漫性大B细胞淋巴瘤(diffuse large B lymphoma,DLBCL)患者血浆中的表达水平及其临床意义。方法利用逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RTPCR)方法检测27例DLBCL患者和27例健康体检者血浆中miR-451的表达水平,并统计分析DLBCL患者血浆中miR-451表达水平与临床病理参数之间的关系。结果 miR-451在DLBCL患者血浆中表达水平明显低于正常对照组[(0.41±0.15)vs.(0.64±0.21)],二者差异具有统计学意义(P<0.01);DLBCL患者血浆中miR-451表达水平在不同性别、年龄、血清LDH水平及原发部位之间差异无统计学意义(P>0.05),而与Ann Arbor分期及IPI评分明显相关(P<0.05)。结论 DLBCL患者血浆中miR-451表达水平降低,可能参与了DLBCL的病理过程。展开更多
Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been consider...Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.展开更多
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).Howev...Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.展开更多
基金supported by the tenth batch of"3221"industrial innovation and scientific research projects in Bengbu City(beng talent[2020]No.8)the 2021 Bengbu Medical College Science and Technology Project[Natural Science,Project Number:2021byzd217].
文摘Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.
文摘目的探讨microRNA-451(miR-451)在食管癌患者血清中的表达水平及其对早期诊断及非手术治疗疗效的判断价值。方法采用实时荧光定量PCR方法检测50例食管癌患者放疗前、后及20例健康对照者血清中miR-451的相对表达量,分析其与临床病理参数及近期疗效的关系。结果食管癌患者血清中miR-451的表达水平明显高于健康对照者(P<0.05),miR-451的ROC曲线下面积(area under the curve,AUC)值取0.911(95%CI=0.844~0.977)时,对食管癌诊断的灵敏度和特异度分别为88%和85%。miR-451的表达水平与食管癌患者的临床分期和淋巴结转移有关。食管癌患者放疗后miR-451表达水平下降(P<0.05),且miR-451的表达水平动态变化与食管癌治疗疗效一致,有效患者miR-451表达水平下降明显高于无效患者(P<0.05)。结论血清miR-451可能对食管癌的早期诊断及非手术治疗疗效的判断有一定的参考价值。
基金supported by the National Natural Science Foundation of China,Nos.82071283(to QH)and 81671130(to QH)Medical Engineering Cross Research Foundation of Shanghai Jiao Tong University of China,No.YG2017MS83(to QH)from Shanghai Municipal Science and Technology Commission Medical Guidance Science and Technology Support Project of China,No.19411968400(to QYM).
文摘Neuroinflammation is a major pathophysiological factor that results in the development of brain injury after cerebral ischemia/reperfusion.Downregulation of microRNA(miR)-455-5p after ischemic stroke has been considered a potential biomarker and therapeutic target for neuronal injury after ischemia.However,the role of miR-455-5p in the post-ischemia/reperfusion inflammatory response and the underlying mechanism have not been evaluated.In this study,mouse models of cerebral ischemia/reperfusion injury were established by transient occlusion of the middle cerebral artery for 1 hour followed by reperfusion.Agomir-455-5p,antagomir-455-5p,and their negative controls were injected intracerebroventricularly 2 hours before or 0 and 1 hour after middle cerebral artery occlusion(MCAO).The results showed that cerebral ischemia/reperfusion decreased miR-455-5p expression in the brain tissue and the peripheral blood.Agomir-455-5p pretreatment increased miR-455-5p expression in the brain tissue,reduced the cerebral infarct volume,and improved neurological function.Furthermore,primary cultured microglia were exposed to oxygen-glucose deprivation for 3 hours followed by 21 hours of reoxygenation to mimic cerebral ischemia/reperfusion.miR-455-5p reduced C-C chemokine receptor type 5 mRNA and protein levels,inhibited microglia activation,and reduced the production of the inflammatory factors tumor necrosis factor-αand interleukin-1β.These results suggest that miR-455-5p is a potential biomarker and therapeutic target for the treatment of cerebral ischemia/reperfusion injury and that it alleviates cerebral ischemia/reperfusion injury by inhibiting C-C chemokine receptor type 5 expression and reducing the neuroinflammatory response.
基金supported by the National Natural Science Foundation of China(Grant No.:82225048)the Dalian Science and Technology Leading Talents Project,China(Grant No.:2019RD15)Sanming Project of Medicine in Shenzhen,China(Grant No.:SZZYSM202106004).
文摘Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Interestingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
