Immunoglobulin G4‐related disease(IgG4‐RD),first identified two decades ago,is an immune‐mediated pro‐inflammatory and profibrotic disease entity affecting multiple organs.The main histopathological features are a...Immunoglobulin G4‐related disease(IgG4‐RD),first identified two decades ago,is an immune‐mediated pro‐inflammatory and profibrotic disease entity affecting multiple organs.The main histopathological features are a dense lymphoplasmacytic infiltrate rich in IgG4+plasma cells,storiform fibrosis,and obliterative phlebitis.The precise immunopathology of IgG4‐RD is still unclear.Substantial research has validated the central role of B cells in IgG4‐RD,which can be further demonstrated by the responsiveness to B cell depletion treatment and the identification of multiple autoantibodies.Whether and how antibodies are pathogenic remains mechanistically undefined,warranting systematic investigation.Through integrative analysis of experimental studies and clinical findings,this review discussed the common characteristics of different classes of antibodies and their potential corresponding unique mechanisms involved in IgG4‐RD.Despite belonging to distinct classes,antibodies share conserved structural features that mediate common effector functions including neutralization and opsonization.In IgG4‐RD pathogenesis,the soluble IgG4 form appears non‐pathogenic,whereas its membrane‐bound counterpart demonstrates enhanced antigen‐binding avidity and facilitates epitope spreading cascades.Among other IgG subclasses,IgG1 emerges as a more potentially pathogenic subclass of antibody.Emerging evidence from multidisciplinary investigations progressively delineates the pathogenetic contributions of IgE and IgM.Systematic interrogation of antibodies with different classes and their pathogenic mechanisms in IgG4‐RD advances our understanding of disease immunopathogenesis while unveiling novel therapeutic targets with translational implications.展开更多
As China enters WTO,more college graduates with higher English proficiency are required.They are required to pass CET4,while some college graduates even forced to pass CET6.However,we learned that even students in som...As China enters WTO,more college graduates with higher English proficiency are required.They are required to pass CET4,while some college graduates even forced to pass CET6.However,we learned that even students in some distinguished universities are lack of the ability of listening and speaking.In this paper,it mainly talks about the role of English listening class in CBT4.展开更多
背景:课题组以往研究证实,骨形态发生蛋白4对生长发育期下颌骨的生长有促进作用,而骨形态发生蛋白2是否能与骨形态发生蛋白4相互促进下颌骨生长目前未见有相关报道。目的:检测生长发育高峰期骨性Ⅱ类错畸形患者血液中骨形态发生蛋白2...背景:课题组以往研究证实,骨形态发生蛋白4对生长发育期下颌骨的生长有促进作用,而骨形态发生蛋白2是否能与骨形态发生蛋白4相互促进下颌骨生长目前未见有相关报道。目的:检测生长发育高峰期骨性Ⅱ类错畸形患者血液中骨形态发生蛋白2和骨形态发生蛋白4的表达情况,以探究骨形态发生蛋白2和骨形态发生蛋白4的表达量与下颌骨生长的关系。方法:生长发育高峰期骨性Ⅰ类错畸形患者为Ⅰ组,以下颌后缩为主的骨性Ⅱ类错畸形患者为Ⅱ组,每组18人。采用实时荧光定量PCR(RT-PCR)分别检测两组血液骨形态发生蛋白2和骨形态发生蛋白4的表达。结果与结论:骨性Ⅱ类错畸形组中骨形态发生蛋白2 mR NA的表达量明显低于对照组骨性Ⅰ类错畸形组(P<0.05),骨性Ⅱ类错畸形组中骨形态发生蛋白4 m RNA的表达量明显低于对照组骨性Ⅰ类错畸形组(P<0.05),骨性Ⅱ组中骨形态发生蛋白2与骨形态发生蛋白4的表达有显著相关性。结果证实,骨形态发生蛋白2和骨形态发生蛋白4在生长发育高峰期的表达量均降低与下颌骨发育不足有密切关系,且骨形态发生蛋白2和骨形态发生蛋白4相互协同,共同参与调节下颌骨的生长。展开更多
目的探讨头框转录因子O家族4(class O of forkhead box transcriptionfactor 4,FOXO4)对喉癌细胞增殖凋亡能力的影响。方法应用Western blot法检测喉癌组织及对应癌旁组织中FOXO4的表达水平。细胞转染FOXO4过表达载体(p-EGFP-C1/FOXO4组...目的探讨头框转录因子O家族4(class O of forkhead box transcriptionfactor 4,FOXO4)对喉癌细胞增殖凋亡能力的影响。方法应用Western blot法检测喉癌组织及对应癌旁组织中FOXO4的表达水平。细胞转染FOXO4过表达载体(p-EGFP-C1/FOXO4组)和空载体(p-EGFP-C1组),同时设置未转染组,未转染组中只加入转染试剂。Western blot法检测转染后细胞中FOXO4蛋白水平。四甲基偶氮唑蓝(MTT)检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测细胞中活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)、Caspase-3、活化的含半胱氨酸的天冬氨酸蛋白水解酶9(Cleaved Caspase-9)、Caspase-9、β-连环蛋白(β-catenin)、Wnt1表达水平。用Wnt/β-catenin信号通路激活剂作用于转染p-EGFP-C1/FOXO4后的喉癌细胞(激活剂组),检测细胞增殖、凋亡情况。结果 FOXO4在喉癌组织中表达水平明显低于癌旁组织(P=0.000)。p-EGFP-C1/FOXO4组细胞中FOXO4表达水平明显高于未转染组(P=0.000)。p-EGFP-C1/FOXO4组细胞存活率及β-catenin、Wnt1水平明显低于未转染组(P=0.002,P=0.004,P=0.006),细胞凋亡率及Cleaved Caspase-3、Caspase-3、Cleaved Caspase-9、C a s p a s e-9表达水平均明显高于未转染组(P=0.0 0 2,P=0.001,h P<0.05,P=0.004,j P<0.05)。Wnt/β-catenin信号通路激活剂可以部分逆转FOXO4抑增殖和促凋亡作用。结论 FOXO4能够促进人喉癌细胞凋亡,抑制喉癌细胞增殖,作用机制可能与Wnt/β-catenin信号通路有关。展开更多
基金National Natural Science Foundation of China,Grant/Award Number:82271847Tongji Hospital Clinical Research Flagship Program,Grant/Award Number:2024TJCR008Research Fund of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology,Grant/Award Number:2023B17。
文摘Immunoglobulin G4‐related disease(IgG4‐RD),first identified two decades ago,is an immune‐mediated pro‐inflammatory and profibrotic disease entity affecting multiple organs.The main histopathological features are a dense lymphoplasmacytic infiltrate rich in IgG4+plasma cells,storiform fibrosis,and obliterative phlebitis.The precise immunopathology of IgG4‐RD is still unclear.Substantial research has validated the central role of B cells in IgG4‐RD,which can be further demonstrated by the responsiveness to B cell depletion treatment and the identification of multiple autoantibodies.Whether and how antibodies are pathogenic remains mechanistically undefined,warranting systematic investigation.Through integrative analysis of experimental studies and clinical findings,this review discussed the common characteristics of different classes of antibodies and their potential corresponding unique mechanisms involved in IgG4‐RD.Despite belonging to distinct classes,antibodies share conserved structural features that mediate common effector functions including neutralization and opsonization.In IgG4‐RD pathogenesis,the soluble IgG4 form appears non‐pathogenic,whereas its membrane‐bound counterpart demonstrates enhanced antigen‐binding avidity and facilitates epitope spreading cascades.Among other IgG subclasses,IgG1 emerges as a more potentially pathogenic subclass of antibody.Emerging evidence from multidisciplinary investigations progressively delineates the pathogenetic contributions of IgE and IgM.Systematic interrogation of antibodies with different classes and their pathogenic mechanisms in IgG4‐RD advances our understanding of disease immunopathogenesis while unveiling novel therapeutic targets with translational implications.
文摘As China enters WTO,more college graduates with higher English proficiency are required.They are required to pass CET4,while some college graduates even forced to pass CET6.However,we learned that even students in some distinguished universities are lack of the ability of listening and speaking.In this paper,it mainly talks about the role of English listening class in CBT4.
文摘背景:课题组以往研究证实,骨形态发生蛋白4对生长发育期下颌骨的生长有促进作用,而骨形态发生蛋白2是否能与骨形态发生蛋白4相互促进下颌骨生长目前未见有相关报道。目的:检测生长发育高峰期骨性Ⅱ类错畸形患者血液中骨形态发生蛋白2和骨形态发生蛋白4的表达情况,以探究骨形态发生蛋白2和骨形态发生蛋白4的表达量与下颌骨生长的关系。方法:生长发育高峰期骨性Ⅰ类错畸形患者为Ⅰ组,以下颌后缩为主的骨性Ⅱ类错畸形患者为Ⅱ组,每组18人。采用实时荧光定量PCR(RT-PCR)分别检测两组血液骨形态发生蛋白2和骨形态发生蛋白4的表达。结果与结论:骨性Ⅱ类错畸形组中骨形态发生蛋白2 mR NA的表达量明显低于对照组骨性Ⅰ类错畸形组(P<0.05),骨性Ⅱ类错畸形组中骨形态发生蛋白4 m RNA的表达量明显低于对照组骨性Ⅰ类错畸形组(P<0.05),骨性Ⅱ组中骨形态发生蛋白2与骨形态发生蛋白4的表达有显著相关性。结果证实,骨形态发生蛋白2和骨形态发生蛋白4在生长发育高峰期的表达量均降低与下颌骨发育不足有密切关系,且骨形态发生蛋白2和骨形态发生蛋白4相互协同,共同参与调节下颌骨的生长。
文摘目的以卷曲受体4(FZD4)为例,探索细胞膜上受体蛋白的表达变化能否作为损伤时间推断的指标。方法 78只大鼠随机分为对照组和损伤后4h、8h、12h、16h、20h、24h、28h、32h、36h、40h、44h和48 h组(n=6)。麻醉后,采用重力锤自由落体方式砸伤大鼠右后肢,取股四头肌处挫伤的组织。应用免疫荧光、real-time PCR和western blotting方法检测肌肉中FZD4蛋白及m RNA的表达量。结果免疫荧光结果显示FZD4表达于骨骼肌细胞膜上,胞浆和细胞核内均未见表达;Real-time PCR结果表明FZD4 m RNA在损伤后8h、12h、36h和40h显著上调(P<0.05),均超过对照组的两倍;Western blotting结果示FZD4蛋白的表达在8h、36h、40h、44h和48h组明显增加(P<0.05),但均未超过对照组的两倍。结论 FZD4 m RNA和蛋白在肌肉挫伤后呈时序性变化规律可作为损伤时间推断的指标,在一定程度上FZD4 m RNA比FZD4更适用于损伤时间推断。
文摘目的探讨头框转录因子O家族4(class O of forkhead box transcriptionfactor 4,FOXO4)对喉癌细胞增殖凋亡能力的影响。方法应用Western blot法检测喉癌组织及对应癌旁组织中FOXO4的表达水平。细胞转染FOXO4过表达载体(p-EGFP-C1/FOXO4组)和空载体(p-EGFP-C1组),同时设置未转染组,未转染组中只加入转染试剂。Western blot法检测转染后细胞中FOXO4蛋白水平。四甲基偶氮唑蓝(MTT)检测细胞增殖,流式细胞术检测细胞凋亡,Western blot检测细胞中活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)、Caspase-3、活化的含半胱氨酸的天冬氨酸蛋白水解酶9(Cleaved Caspase-9)、Caspase-9、β-连环蛋白(β-catenin)、Wnt1表达水平。用Wnt/β-catenin信号通路激活剂作用于转染p-EGFP-C1/FOXO4后的喉癌细胞(激活剂组),检测细胞增殖、凋亡情况。结果 FOXO4在喉癌组织中表达水平明显低于癌旁组织(P=0.000)。p-EGFP-C1/FOXO4组细胞中FOXO4表达水平明显高于未转染组(P=0.000)。p-EGFP-C1/FOXO4组细胞存活率及β-catenin、Wnt1水平明显低于未转染组(P=0.002,P=0.004,P=0.006),细胞凋亡率及Cleaved Caspase-3、Caspase-3、Cleaved Caspase-9、C a s p a s e-9表达水平均明显高于未转染组(P=0.0 0 2,P=0.001,h P<0.05,P=0.004,j P<0.05)。Wnt/β-catenin信号通路激活剂可以部分逆转FOXO4抑增殖和促凋亡作用。结论 FOXO4能够促进人喉癌细胞凋亡,抑制喉癌细胞增殖,作用机制可能与Wnt/β-catenin信号通路有关。
