Concerns about the long-term safety and efficacy of glibenclamide(GLIB),a type 2 diabetes mellitus(T2DM)treatment,have been reported[1].Recent evidence indicates the gut microbiota composition significantly affects ho...Concerns about the long-term safety and efficacy of glibenclamide(GLIB),a type 2 diabetes mellitus(T2DM)treatment,have been reported[1].Recent evidence indicates the gut microbiota composition significantly affects host glucose metabolism and drugbioavailability,increasingthe efficacy of T2DM therapy[2].In this context,probiotic-drug coadministration,an emerging adjunct approach for treating metabolic diseases,improves therapeutic outcomes and ameliorates side effects[3].展开更多
背景:肿瘤双向调控因子核因子κB激活激酶的研究成果逐年增多,但是却没有相关文献计量学分析。目的:通过文献计量学分析肿瘤逃避因子核因子κB激活激酶的研究现状、热点及趋势。方法:基于Web of Science核心合集中的SCIE数据库筛选近10...背景:肿瘤双向调控因子核因子κB激活激酶的研究成果逐年增多,但是却没有相关文献计量学分析。目的:通过文献计量学分析肿瘤逃避因子核因子κB激活激酶的研究现状、热点及趋势。方法:基于Web of Science核心合集中的SCIE数据库筛选近10年来核因子κB激活激酶相关研究文献,导入Cite Space 6.3.R1软件中分别以国家(地区)、作者、机构、参考文献和关键词5个选项进行文献计量及可视化分析,并运用Origin 2021软件绘制相关统计图。结果与结论:核因子κB激活激酶的发文量、文献共被引次数呈现上升的趋势,Chen,Dan-Dan、Gui,Jian-Fang、Qin,Qiwei和Li,Shun 4位作者发文量最多(11篇),中国科学院、中国科学院大学、浙江大学、中国农业科学院、武汉大学的发文量较大(>50篇)。近10年来关于核因子κB激活激酶的研究热点主要集中在innate immunity、c GAS-STING pathway、NF-κB、inflammation、optineurin、expression、cancer等模块。结果表明,近年来各国学者在相关领域进行了持续且深入的研究,核因子κB激活激酶在自身免疫系统、信号通路、基因表达、肿瘤防治等方面显示出巨大的科研潜力。但是学者之间、机构之间的学术合作并不紧密,今后学者应加强合作与交流,把握核因子κB激活激酶的研究热点与趋势,拓展在疾病领域中的研究范围,为进一步阐明疾病的药效机制和病理变化提供更多证据。展开更多
The published article titled“Long Noncoding RNA PVT1 PromotesMelanoma Progression via Endogenous Sponging miR-26b”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.675–681.DOI:10.3727/096504017X14920318...The published article titled“Long Noncoding RNA PVT1 PromotesMelanoma Progression via Endogenous Sponging miR-26b”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.675–681.DOI:10.3727/096504017X14920318811730 URL:https://www.techscience.com/or/v26n5/56680 Following the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 An imbalance in the rumen microbiota caused by high-concentrate diets(HCD)is a significant endogenous trigger of mastitis.However,the underlying mechanisms remain largely unknown.Microbial extracellular ves...Background An imbalance in the rumen microbiota caused by high-concentrate diets(HCD)is a significant endogenous trigger of mastitis.However,the underlying mechanisms remain largely unknown.Microbial extracellular vesicles(mEVs)are critical mediators of microbe-host communication.However,the role of mEVs in rumen microbiota-mediated mastitis has not yet been reported.In this study,we used an HCD-induced rumen microbiota dysbiosis model to investigate the role of mEVs-derived from rumen microbiota in the pathogenesis of mastitis.Results Our results indicate that HCD leads to mastitis and systemic inflammation.Meanwhile,HCD-fed goats exhibited substantial rumen microbiota dysbiosis and the disruption of the rumen barrier.Transplanting rumen microbiota from HCD goats into mice induced both mastitis and systemic inflammation in the recipients.Specifically,HCD increases the production of mEVs carrying microbial DNA,which can translocate across the compromised rumen barrier to the mammary gland,triggering a mammary inflammatory response via activation of the cGAS-STING-NF-κB/NLRP3 pathway.Furthermore,treating mice with mEVs isolated from the rumen fluid of HCD goats directly induced mastitis,whereas depletion of microbial DNA attenuated mEVs-induced mastitis.Conclusion Our findings suggest that HCD induces rumen microbiota dysbiosis and impairs rumen barrier function.This dysfunction leads to an increase in microbial DNA-containing mEVs,which subsequently leak into the mammary gland.Once there,these mEVs activate the cGAS-STING-NF-κB/NLRP3 signaling pathway,ultimately inducing mastitis.This study provides a new perspective on the“rumen microbiota-mammary gland axis”and enhances the understanding of the pathogenesis of mastitis.展开更多
Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular st...Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.展开更多
基金supported by the National Natural Science Foundation of China(32525049).
文摘Concerns about the long-term safety and efficacy of glibenclamide(GLIB),a type 2 diabetes mellitus(T2DM)treatment,have been reported[1].Recent evidence indicates the gut microbiota composition significantly affects host glucose metabolism and drugbioavailability,increasingthe efficacy of T2DM therapy[2].In this context,probiotic-drug coadministration,an emerging adjunct approach for treating metabolic diseases,improves therapeutic outcomes and ameliorates side effects[3].
文摘背景:肿瘤双向调控因子核因子κB激活激酶的研究成果逐年增多,但是却没有相关文献计量学分析。目的:通过文献计量学分析肿瘤逃避因子核因子κB激活激酶的研究现状、热点及趋势。方法:基于Web of Science核心合集中的SCIE数据库筛选近10年来核因子κB激活激酶相关研究文献,导入Cite Space 6.3.R1软件中分别以国家(地区)、作者、机构、参考文献和关键词5个选项进行文献计量及可视化分析,并运用Origin 2021软件绘制相关统计图。结果与结论:核因子κB激活激酶的发文量、文献共被引次数呈现上升的趋势,Chen,Dan-Dan、Gui,Jian-Fang、Qin,Qiwei和Li,Shun 4位作者发文量最多(11篇),中国科学院、中国科学院大学、浙江大学、中国农业科学院、武汉大学的发文量较大(>50篇)。近10年来关于核因子κB激活激酶的研究热点主要集中在innate immunity、c GAS-STING pathway、NF-κB、inflammation、optineurin、expression、cancer等模块。结果表明,近年来各国学者在相关领域进行了持续且深入的研究,核因子κB激活激酶在自身免疫系统、信号通路、基因表达、肿瘤防治等方面显示出巨大的科研潜力。但是学者之间、机构之间的学术合作并不紧密,今后学者应加强合作与交流,把握核因子κB激活激酶的研究热点与趋势,拓展在疾病领域中的研究范围,为进一步阐明疾病的药效机制和病理变化提供更多证据。
文摘The published article titled“Long Noncoding RNA PVT1 PromotesMelanoma Progression via Endogenous Sponging miR-26b”has been retracted from Oncology Research,Vol.26,No.5,2018,pp.675–681.DOI:10.3727/096504017X14920318811730 URL:https://www.techscience.com/or/v26n5/56680 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.
基金supported by the National Natural Science Foundation of China(32330105 and 32301247)National Key R&D Program of China(2023YFD1801100)。
文摘Background An imbalance in the rumen microbiota caused by high-concentrate diets(HCD)is a significant endogenous trigger of mastitis.However,the underlying mechanisms remain largely unknown.Microbial extracellular vesicles(mEVs)are critical mediators of microbe-host communication.However,the role of mEVs in rumen microbiota-mediated mastitis has not yet been reported.In this study,we used an HCD-induced rumen microbiota dysbiosis model to investigate the role of mEVs-derived from rumen microbiota in the pathogenesis of mastitis.Results Our results indicate that HCD leads to mastitis and systemic inflammation.Meanwhile,HCD-fed goats exhibited substantial rumen microbiota dysbiosis and the disruption of the rumen barrier.Transplanting rumen microbiota from HCD goats into mice induced both mastitis and systemic inflammation in the recipients.Specifically,HCD increases the production of mEVs carrying microbial DNA,which can translocate across the compromised rumen barrier to the mammary gland,triggering a mammary inflammatory response via activation of the cGAS-STING-NF-κB/NLRP3 pathway.Furthermore,treating mice with mEVs isolated from the rumen fluid of HCD goats directly induced mastitis,whereas depletion of microbial DNA attenuated mEVs-induced mastitis.Conclusion Our findings suggest that HCD induces rumen microbiota dysbiosis and impairs rumen barrier function.This dysfunction leads to an increase in microbial DNA-containing mEVs,which subsequently leak into the mammary gland.Once there,these mEVs activate the cGAS-STING-NF-κB/NLRP3 signaling pathway,ultimately inducing mastitis.This study provides a new perspective on the“rumen microbiota-mammary gland axis”and enhances the understanding of the pathogenesis of mastitis.
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the National Italian Research Council(CNR)“Progetto DSB.AD007.305.001”to Monica Rinaldi。
文摘Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.
