Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that ...Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.展开更多
Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed ...Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.The primary treatment strategies for HCC currently include liver transplantation and surgical resection.However,these methods often yi...BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.The primary treatment strategies for HCC currently include liver transplantation and surgical resection.However,these methods often yield unsatisfactory outcomes,leading to a poor prognosis for many patients.This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients.AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC.METHODS Gene expression,clinical parameters,HCC-related radiomics,and fibroblastrelated genes were acquired from public databases.A gene model was developed,and its clinical efficacy was assessed statistically.Drug sensitivity analysis was conducted with identified hub genes.Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes.A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes.RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model.This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis.A negative correlation was observed between EZH2 expression and drug sensitivity.Elevated EZH2 expression was linked to poorer prognosis,and its diagnostic value in HCC surpassed that of the risk model.A radiomics model,developed using a logistic algorithm,also showed superior efficiency in predicting EZH2 expression.The Radscore was higher in the group with high EZH2 expression.A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients.CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy.A radiomics model,developed using a logistic algorithm,efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.展开更多
目的探讨EZH2基因在肝细胞癌(HCC)中的表达水平及临床价值,为HCC的诊断和靶向治疗提供依据。方法利用THE HUMAN PROTEIN ATLAS、GEPIA、TIMER、Oncomine数据库在线分析EZH2基因在健康人体各器官组织、正常肝组织和HCC组织中的mRNA表达...目的探讨EZH2基因在肝细胞癌(HCC)中的表达水平及临床价值,为HCC的诊断和靶向治疗提供依据。方法利用THE HUMAN PROTEIN ATLAS、GEPIA、TIMER、Oncomine数据库在线分析EZH2基因在健康人体各器官组织、正常肝组织和HCC组织中的mRNA表达情况。利用Kaplan-Meier Plotter和Ualcan数据库的HCC数据集在线分析患者生存期与EZH2表达的关系。通过String数据库在线检索EZH2的相关蛋白网络图,并进行功能注释和KEGG通路富集分析。TIMER数据分析免疫浸润物的表达水平及对肝癌患者生存预后的影响。结果EZH2基因在各级HCC组织中的mRNA和蛋白均显著高于正常肝组织。EZH2基因的差异表达水平与病理分级、临床分期以及患者体质量显著相关。生存分析发现,EZH2基因高表达水平的HCC患者的总生存期(OS)、无病生存期(PFS)、无远处转移生存期(RFS)、后进展生存期(DDS)显著缩短。String数据库分析发现,EZH2基因相关蛋白主要富集于12类细胞学组分、5类分子功能和7类生物学过程,并参与了4条信号通路。EZH2基因与增殖相关基因BUB1、KIF4A、TPX2、MELK、DLGAP5、KIF20A等共同表达。TIMER数据库分析显示,EZH2 mRNA在HCC免疫微环境中与肿瘤纯度、B细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞的表达水平呈正相关。结论HCC组织中EZH2基因呈现高表达水平,其表达水平与HCC的发生、发展及预后密切相关,可能是肝癌潜在的预后生物学标志物及治疗靶标。展开更多
基金financially supported by the National Natural Science Foundation of China,Nos.82172104(to CX),81873767(to HZ)a grant from Jiangsu Provincial Research Hospital,Nos.YJXYY202204(to HZ),YJXYY202204-ZD04(to HZ)+5 种基金a grant from Jiangsu Provincial Key Medical CenterJiangsu Provincial Medical Innovation Center,No.CXZX202212Jiangsu Provincial Medical Key Discipline,No.ZDXK202240the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)Technology Project of Nantong,No.MS22022008(to HZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.SJCX21_1457(to WW)。
文摘Demyelination and remyelination have been major focal points in the study of peripheral nerve regeneration following peripheral nerve injury.Notably,the gene regulatory network of regenerated myelin differs from that of native myelin.Silencing of enhancer of zeste homolog 2(EZH2)hinders the differentiation,maturation,and myelination of Schwann cells in vitro.To further determine the role of EZH2 in myelination and recovery post-peripheral nerve injury,conditional knockout mice lacking Ezh2 in Schwann cells(Ezh2^(fl/fl);Dhh-Cre and Ezh2^(fl/fl);Mpz-Cre)were generated.Our results show that a significant proportion of axons in the sciatic nerve of Ezh2-depleted mice remain unmyelinated.This highlights the crucial role of Ezh2 in initiating Schwann cell myelination.Furthermore,we observed that 21 days after inducing a sciatic nerve crush injury in these mice,most axons had remyelinated at the injury site in the control nerve,while Ezh2^(fl/fl);Mpz-Cre mice had significantly fewer remyelinated axons compared with their wild-type littermates.This suggests that the absence of Ezh2 in Schwann cells impairs myelin formation and remyelination.In conclusion,EZH2 has emerged as a pivotal regulatory factor in the process of demyelination and myelin regeneration following peripheral nerve injury.Modulating EZH2 activity during these processes may offer a promising therapeutic target for the treatment of peripheral nerve injuries.
文摘Following the publication,concerns have been raised about a number of figures in this article.An unexpected area of similarity was identified in terms of the cellular data,where the results from differently performed experiments were intended to have been shown,although the areas immediately surrounding this area featured comparatively different distributions of cells.In addition,the western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is the most common subtype of liver cancer.The primary treatment strategies for HCC currently include liver transplantation and surgical resection.However,these methods often yield unsatisfactory outcomes,leading to a poor prognosis for many patients.This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients.AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC.METHODS Gene expression,clinical parameters,HCC-related radiomics,and fibroblastrelated genes were acquired from public databases.A gene model was developed,and its clinical efficacy was assessed statistically.Drug sensitivity analysis was conducted with identified hub genes.Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes.A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes.RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model.This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis.A negative correlation was observed between EZH2 expression and drug sensitivity.Elevated EZH2 expression was linked to poorer prognosis,and its diagnostic value in HCC surpassed that of the risk model.A radiomics model,developed using a logistic algorithm,also showed superior efficiency in predicting EZH2 expression.The Radscore was higher in the group with high EZH2 expression.A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients.CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy.A radiomics model,developed using a logistic algorithm,efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.
文摘目的探讨EZH2基因在肝细胞癌(HCC)中的表达水平及临床价值,为HCC的诊断和靶向治疗提供依据。方法利用THE HUMAN PROTEIN ATLAS、GEPIA、TIMER、Oncomine数据库在线分析EZH2基因在健康人体各器官组织、正常肝组织和HCC组织中的mRNA表达情况。利用Kaplan-Meier Plotter和Ualcan数据库的HCC数据集在线分析患者生存期与EZH2表达的关系。通过String数据库在线检索EZH2的相关蛋白网络图,并进行功能注释和KEGG通路富集分析。TIMER数据分析免疫浸润物的表达水平及对肝癌患者生存预后的影响。结果EZH2基因在各级HCC组织中的mRNA和蛋白均显著高于正常肝组织。EZH2基因的差异表达水平与病理分级、临床分期以及患者体质量显著相关。生存分析发现,EZH2基因高表达水平的HCC患者的总生存期(OS)、无病生存期(PFS)、无远处转移生存期(RFS)、后进展生存期(DDS)显著缩短。String数据库分析发现,EZH2基因相关蛋白主要富集于12类细胞学组分、5类分子功能和7类生物学过程,并参与了4条信号通路。EZH2基因与增殖相关基因BUB1、KIF4A、TPX2、MELK、DLGAP5、KIF20A等共同表达。TIMER数据库分析显示,EZH2 mRNA在HCC免疫微环境中与肿瘤纯度、B细胞、CD8+T细胞、CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞的表达水平呈正相关。结论HCC组织中EZH2基因呈现高表达水平,其表达水平与HCC的发生、发展及预后密切相关,可能是肝癌潜在的预后生物学标志物及治疗靶标。
