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
BACKGROUND Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal ...BACKGROUND Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma(HCC).AIM To understand the mechanism of exosomal microRNA-224(miR-224) in the development of HCC and evaluate its diagnostic and prognostic value.METHODS Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis.RESULTSBy targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.CONCLUSION Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.展开更多
Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD mo...Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.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 Scientific and Technological Research Project of Henan Province,No.162102310024
文摘BACKGROUND Exosomes contain proteins, lipids, and biological molecules such as DNA and RNA. Nucleic acids in exosomes are a group of molecules that can act as biomarkers. Currently, there are many reports on exosomal microRNAs, which are ideal biomarkers for the early diagnosis of cancer. However, there are few reports on the role of exosomal microRNAs in the diagnosis and prognosis of hepatocellular carcinoma(HCC).AIM To understand the mechanism of exosomal microRNA-224(miR-224) in the development of HCC and evaluate its diagnostic and prognostic value.METHODS Cell culture and transfection of exosomal miRNA-224, real-time quantitative PCR, luciferase reporter assay, and other methods were used to find new biomarkers related to the development of HCC that can be used to diagnose HCC and predict HCC prognosis.RESULTSBy targeting glycine N-methyltransferase, incubating exosomes with miR-224 mimic resulted in a significant increase in cell proliferation compared to that of the control group, while incubation with the miR-224 inhibitor significantly reduced cell proliferation. The same results were obtained for the cell invasion assay. Serum exosomal miR-224 did have some ability to differentiate patients with HCC from healthy controls, with an area under the curve of 0.910, and HCC patients with higher serum exosomal miR-224 expression had lower overall survival.CONCLUSION Exosomal miR-224 is a tumor promotor and can be a marker of diagnosis and prognosis of HCC patients, however, its ability to distinguish liver diseases needs further verification.
基金supported by the National Natural Science Foundation of China[grant numbers 81630018,82070538,,81870374]Guangdong Science and Technology Department[grant number 2017A030306021]Guangzhou Science and Technology Department[grant number 202002030041].
文摘Background:Crohn’s disease(CD)has a tendency for recurrence and requires adequate monitoring and personalized treatment.Since endoscopy is considerably invasive,serum biomarkers are required as alternatives for CD monitoring.Toward this,exosomal microRNAs(miRNAs)may serve as promising candidates.In this study,we aimed to assess the role of serum exosomal microRNA-144-3p(miR-144-3p)as a biomarker for CD monitoring.Methods:We prospectively recruited 154 patients without a history of surgery(Cohort 1)and 75 patients who were to undergo intestinal resection(Cohort 2).Serum samples were collected from Cohort 1 before colonoscopy and from Cohort 2 before surgery and during post-operative colonoscopic examination.The serum levels of exosomal miR-144-3p were measured using quantitative reverse-transcription polymerase chain reaction(PCR).Correlations between relative exosomal miR-144-3p levels,disease activity,and disease behavior were analysed.The area under the receiver-operating characteristic curve(AUC)was used to assess the predictive value of exosomal miR-144-3p regarding mucosal activity and postoperative recurrence.Results:A 3.33-fold increase in serum exosomal miR-144-3p levels was recorded in patients with CD compared with those in healthy controls(P<0.001).The exosomalmiR-144-3p levels were positively correlated with the simple endoscopic score of CD(q=0.547,P<0.001)as well as the Rutgeerts score(q=0.478,P<0.001).Elevated exosomalmiR-144-3p levels were correlated with the penetrating disease with high specificity(100%[95%confidence interval,95.1%–100%]).The accuracy of exosomalmiR-144-3p for identifying post-operative recurrence was higher than that of C-reactive protein(CRP)(AUC,0.775 vs 0.639;P<0.001).Conclusions:Serum exosomal miR-144-3p is a reliable biomarker of mucosal inflammation and penetrating CD.It may identify endoscopic CD recurrence after intestinal resection with higher accuracy than CRP testing.
