目的:分析二肽基肽酶样蛋白-6(dipeptidyl-peptidase-like protein 6,DPPX)抗体相关脑炎患者的临床特征。方法:对2016年1月—2025年2月南京医科大学附属脑科医院就诊的5例DPPX抗体相关脑炎患者的临床特点、脑电图、磁共振成像(magnetic ...目的:分析二肽基肽酶样蛋白-6(dipeptidyl-peptidase-like protein 6,DPPX)抗体相关脑炎患者的临床特征。方法:对2016年1月—2025年2月南京医科大学附属脑科医院就诊的5例DPPX抗体相关脑炎患者的临床特点、脑电图、磁共振成像(magnetic resonance imaging,MRI)及预后进行回顾性研究。结果:5例均为男性,年龄14~56岁。5例患者血清DPPX抗体均为阳性,滴度1∶100~1∶10,其中1例合并血清接触蛋白关联蛋白2(contactin-associated protein-like 2,CASPR2)抗体阳性,4例脑脊液DPPX抗体阴性,1例滴度1∶1。2例患者以行为异常起病,1例以癫痫发作起病,1例以记忆力减退起病,1例合并CASPR2抗体阳性患者以多部位游走性肌阵挛起病。4例患者头颅MRI正常,1例头颅MRI提示双侧颞叶异常信号。以癫痫发作起病的患者脑电图背景重度异常合并左前颞尖波、尖慢波频发。结论:DPPX抗体相关脑炎临床表现具有异质性,早期诊断与鉴别困难,免疫治疗有效,易复发。展开更多
Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.T...Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.This work investigates the role of prefoldin subunit 6-like protein(PFDN6L)in shaping LCSC traits and promoting or restraining HCC progression.Methods:PFDN6L,a cytoskeleton-associated chaperone,was studied using multiple in vitro assays—cell growth evaluation,cell cycle profiling,and spheroid culture—alongside analyses of stemness-associated markers(SOX2,CD133,CD44).Tumorigenic capacity was assessed in xenograft mouse models,and signaling pathway interrogation was performed to define underlying mechanisms.Results:In patient samples,higher PFDN6L expression correlated with improved survival outcomes.Forced expression of PFDN6L induced G2/M arrest,diminished sphere formation,and reduced pluripotency marker expression,whereas knockdown accelerated in vivo tumor formation.Mechanistic experiments demonstrated that PFDN6L suppressesmalignancy by simultaneously dampening AKT and ERK1/2 activation,thereby impairing oncogenic signaling cascades.Conclusion:PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis.Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action,supporting its potential as a prognostic biomarker and therapeutic target in HCC.展开更多
AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients un...AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.展开更多
基金supported by the National Natural Science Foundation of China(Grant Numbers 82350117,82160476,32360046,82260462)First-Class Discipline Team of Kunming Medical University 2024XKTDYS07,Yunnan Provincial Department of Science and Technology Key Research and Development Plan for Social Development Special Projects(202403AC100022)+4 种基金The Fundamental Research Project of Yunnan Provincial Department of Science and Technology(202301AT070129)the Joint Special Funds for the Department of Science and Technology of Yunnan Province KunmingMedical University(Grant Number 202401AY070001-360)the Yunnan Provincial Department of Education Science Research Fund Project(Grant Number 2023Y0655,2024Y234)Yunnan Province Science and Technology Talents and Platform Plan Project(202305AF150067)Beijing Sci-Tech Innovation Medical Development Foundation KC2023-JX-0288-PM94.
文摘Background:Liver cancer stem cells(LCSCs)are recognized as pivotal drivers of hepatocellular carcinoma(HCC)progression;however,the molecular mechanisms maintaining their stem-like phenotype remain largely unresolved.This work investigates the role of prefoldin subunit 6-like protein(PFDN6L)in shaping LCSC traits and promoting or restraining HCC progression.Methods:PFDN6L,a cytoskeleton-associated chaperone,was studied using multiple in vitro assays—cell growth evaluation,cell cycle profiling,and spheroid culture—alongside analyses of stemness-associated markers(SOX2,CD133,CD44).Tumorigenic capacity was assessed in xenograft mouse models,and signaling pathway interrogation was performed to define underlying mechanisms.Results:In patient samples,higher PFDN6L expression correlated with improved survival outcomes.Forced expression of PFDN6L induced G2/M arrest,diminished sphere formation,and reduced pluripotency marker expression,whereas knockdown accelerated in vivo tumor formation.Mechanistic experiments demonstrated that PFDN6L suppressesmalignancy by simultaneously dampening AKT and ERK1/2 activation,thereby impairing oncogenic signaling cascades.Conclusion:PFDN6L acts as a negative regulator of LCSC-driven tumorigenesis.Its dual blockade of AKT and ERK pathways forms the mechanistic basis of its tumor-suppressive action,supporting its potential as a prognostic biomarker and therapeutic target in HCC.
文摘AIM:To investigate the effect of Tenascin C(TNC)on the expression of pro-inflammatory cytokines and matrixmetalloproteinases in human cardiac myofibroblasts(CMF).METHODS:CMF were isolated and cultured from patients undergoing coronary artery bypass grafting.Cultured cells were treated with either TNC(0.1μmol/L,24 h)or a recombinant protein corresponding to different domains of the TNC protein;fibrinogen-like globe(FBG)and fibronectin typeⅢ-like repeats(TNⅢ5-7)(both 1μmol/L,24 h).The expression of the proinflammatory cytokines;interleukin(IL)-6,IL-1β,TNFαand the matrix metalloproteinases;MMPs(MMP1,2,3,9,10,MT1-MMP)was assessed using real time RT-PCR and western blot analysis.RESULTS:TNC increased both IL-6 and MMP3(P<0.01)mR NA levels in cultured human CMF but had no significant effect on the other markers studied.The increase in IL-6 mR NA expression was mirrored by an increase in protein secretion as assessed by enzymelinked immunosorbant assay(P<0.01).Treating CMF with the recombinant protein FBG increased IL-6mR NA and protein(P<0.01)whereas the recombinant protein TNⅢ5-7 had no effect.Neither FBG nor TNⅢ5-7 had any significant effect on MMP3 expression.The expression of toll-like receptor 4(TLR4)in human CMF was confirmed by real time RT-PCR,western blot and immunohistochemistry.Pre-incubation of cells with TLR4neutralising antisera attenuated the effect of both TNC and FBG on IL-6 mR NA and protein expression.CONCLUSION:TNC up-regulates IL-6 expression in human CMF,an effect mediated through the FBG domain of TNC and via the TLR4 receptor.
