Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bi...Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.展开更多
文摘目的明确TPT1-AS1在胃癌及远端基本正常组织中的差异表达,探讨其表达水平与胃癌临床病理特征的相关性,评价其作为胃癌生物标志物的可能性。方法采用实时荧光定量PCR(quantitative real-time PCR, qRT-PCR)方法检测TPT1-AS1在胃癌患者的肿瘤组织(73例)及远端基本正常组织(66例)标本的表达水平。结果TPT1-AS1在胃癌组织中的表达水平较远端基本正常组织低表达,其表达水平与胃癌临床病理特征如年龄、性别、肿瘤大小、肿瘤生长部位等无相关性( P >0.05)。TPT1-AS1作为胃癌诊断生物标志物时,曲线下面积、灵敏度及特异性分别为0.641、72.6%及51.5%。生存分析结果显示,高表达患者预后优于低表达患者,但差异无统计学意义( P >0.05)。结论TPT1-AS1在胃癌组织中表达降低,具有作为胃癌诊断生物标志物的可能,本研究为胃癌的早诊、早治提供新的线索。
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
基金Study on the Correlation between the Regulation of the miR-26a/PTEN Axis by lncRNA DLX6-AS1 and Post-Hepatitis Liver Fibrosis(Project No.:YKK22233)。
文摘Objective:To elucidate the role and clinical potential of the lncRNA DLX6-AS1/miR-26a/PTEN axis in liver fibrosis.Methods:Systematic studies were conducted using cellular and animal models through causal validation,bivariate experiments,single-cell sequencing,ROC analysis of clinical samples,and humanized mouse models.Results:LncRNA DLX6-AS1 inhibited PTEN by adsorbing miR-26a,promoting hepatic stellate cell activation in a dose/time-dependent manner;the axis demonstrated excellent diagnostic performance(AUC>0.9),and its inhibitors effectively reversed fibrosis in vivo.Conclusion:This study provides new biomarkers and targeted therapeutic strategies for liver fibrosis.
