家族性高胆固醇血症(familial hypercholesterolemia,FH)的临床特征为血总胆固醇升高,尤其是低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-c)升高,沉积于组织,形成皮肤或肌腱黄色瘤,导致动脉粥样硬化甚至早发冠心病。F...家族性高胆固醇血症(familial hypercholesterolemia,FH)的临床特征为血总胆固醇升高,尤其是低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-c)升高,沉积于组织,形成皮肤或肌腱黄色瘤,导致动脉粥样硬化甚至早发冠心病。FH的发病机制为LDL受体(LDL receptor,LDLR)或apoB基因突变引起LDL受体途径功能缺陷,主要为常染色体显性遗传疾患,具有基因剂量效应;部分患者为常染色体隐性遗传,机制为LDL受体衔接蛋白1(LDL receptor adaptor protein 1,LDLRAP1)失功能型突变,导致LDL内化活性降低。罕见的人类枯草溶菌素转化酶9(proprotein convertase subtilisin/kexin type 9,PCSK9)发生功能型突变也可引起严重的FH表型。PCSK9通过降解LDLR蛋白间接下调LDL受体途径,其失功能突变可致血浆LDL水平下降。因此PCSK9是目前降脂药物的研究热点。展开更多
Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery...Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery.FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription,cytoarchitecture,cell proliferation,and signal transduction.Several studies have validated the importance of FHL1 in muscle development,myopathy,and cardiovascular diseases.Mutations in the FHL1 gene are associated with various myopathies.Recently,FHL1 was identified as a major host factor for chikungunya virus(CHIKV)infection in both humans and mice.Based on more recent findings over the last decade,FHL1 is proposed to play a dual role in cancer progression.On the one hand,FHL1 expression is suppressed in several cancer types,which correlates with increased metastatic disease and decreased survival.Moreover,FHL1 is reported to inhibit tum or cell growth and migration by associating with diverse signals,such as TGF-P and ER,and therefore considered a tumor suppressor.On the other hand,FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation,reflecting complex roles in cancer.This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.展开更多
A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall f...A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall focus on the regulation of their development and function in health and disease. T FH can be characterized on the basis of their phenotype and the pattern of secretion of cytokines. This fact is useful to study their participation in the generation of antibody deficiency in primary immunodeficiency diseases such as common variable immunodeficiency, X-linked hyper Ig M syndrome orX-linked lymphoproliferative disease. Increased numbers of T FH have been demonstrated in several autoimmune diseases and are thought to play a role in the development of autoantibodies. In chronic viral infections caused by the human immunodeficiency virus, hepatitis B or C virus, increased circulating T FH have been observed, but their role in the protective immune response to these agents is under discussion. Likewise, an important role of T FH in the control of some experimental protozoan infections has been proposed, and it will be important to assess their relevance in order to design effective vaccination strategies.展开更多
文摘家族性高胆固醇血症(familial hypercholesterolemia,FH)的临床特征为血总胆固醇升高,尤其是低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-c)升高,沉积于组织,形成皮肤或肌腱黄色瘤,导致动脉粥样硬化甚至早发冠心病。FH的发病机制为LDL受体(LDL receptor,LDLR)或apoB基因突变引起LDL受体途径功能缺陷,主要为常染色体显性遗传疾患,具有基因剂量效应;部分患者为常染色体隐性遗传,机制为LDL受体衔接蛋白1(LDL receptor adaptor protein 1,LDLRAP1)失功能型突变,导致LDL内化活性降低。罕见的人类枯草溶菌素转化酶9(proprotein convertase subtilisin/kexin type 9,PCSK9)发生功能型突变也可引起严重的FH表型。PCSK9通过降解LDLR蛋白间接下调LDL受体途径,其失功能突变可致血浆LDL水平下降。因此PCSK9是目前降脂药物的研究热点。
基金grants from the National Natural Science Foundation of China(Grant No.81730071,81472734,and 81670626)Ministry of Science and Technology of China(Grant No.2016YFC1302103,and 2015CB553906)+1 种基金Beijing Natural Science Foundation grants(Grant No.7171005,7202084,and 7202080)Peking University grants(Grant No.BMU2018JC004 and BMU20120314)to H.Z.
文摘Four and a half LIM domains protein 1(FH L1),as the name suggests,contains four and a half LIM domains capable o f interacting with various molecules,including structural proteins,kinases,and transcriptional machinery.FHL1 contains a zinc-finger domain and performs diverse roles in regulation of gene transcription,cytoarchitecture,cell proliferation,and signal transduction.Several studies have validated the importance of FHL1 in muscle development,myopathy,and cardiovascular diseases.Mutations in the FHL1 gene are associated with various myopathies.Recently,FHL1 was identified as a major host factor for chikungunya virus(CHIKV)infection in both humans and mice.Based on more recent findings over the last decade,FHL1 is proposed to play a dual role in cancer progression.On the one hand,FHL1 expression is suppressed in several cancer types,which correlates with increased metastatic disease and decreased survival.Moreover,FHL1 is reported to inhibit tum or cell growth and migration by associating with diverse signals,such as TGF-P and ER,and therefore considered a tumor suppressor.On the other hand,FHL1 can function as an oncogenic protein that promotes tumor progression upon phosphorylation,reflecting complex roles in cancer.This review primarily focuses on the dual role and underlying mechanisms of action of FHL1 in human cancer progression and its clinical relevance.
基金Supported by Consejo Nacional de Investigaciones Científicas y Técnicas,CONICET,PIP Nos.0032 and 11220120100619CO
文摘A correct antibody response requires the participation of both B and T lymphocytes and antigen presenting cells. In this review we address the role of follicular helper T lymphocytes(T FH) in this reaction. We shall focus on the regulation of their development and function in health and disease. T FH can be characterized on the basis of their phenotype and the pattern of secretion of cytokines. This fact is useful to study their participation in the generation of antibody deficiency in primary immunodeficiency diseases such as common variable immunodeficiency, X-linked hyper Ig M syndrome orX-linked lymphoproliferative disease. Increased numbers of T FH have been demonstrated in several autoimmune diseases and are thought to play a role in the development of autoantibodies. In chronic viral infections caused by the human immunodeficiency virus, hepatitis B or C virus, increased circulating T FH have been observed, but their role in the protective immune response to these agents is under discussion. Likewise, an important role of T FH in the control of some experimental protozoan infections has been proposed, and it will be important to assess their relevance in order to design effective vaccination strategies.
