BAFF在自身免疫性疾病方面的研究进展

自身免疫性疾病的特征是B细胞耐受丧失,B细胞激活因子（B cell activating factor belonging to theTNF family,BAFF）通过与受体结合,对B细胞的增殖、存活起重要作用。BAFF转基因小鼠易出现自身免疫性疾病。因此,拮抗或抑制BAFF的表达可能是治疗自身免疫性疾病的靶点。本文主要对BAFF在自身免疫性疾病方面的研究进展进行综述。     

B淋巴细胞激活因子研究进展

B淋巴细胞刺激因子(BAFF)在B细胞免疫中具有促进B细胞的分化、成熟,调节体液中的抗体反应等重要的作用。然而过多的BANFF表达可使B细胞存活时间延长,B细胞数目增多,活性过高而导致自身免疫性疾病。BAFF与细胞表面的三种受体结合,执行着并不完全相同的功能。由于BAFF在B细胞发育、分化及白体免疫性疾病(特别是系统性红斑狼疮)中具有重要的作用,BAFF及其下游的信号转导因子成为疾病治疗的理想靶位。     

人sBCMA cDNA的克隆、高可溶性融合表达及活性分析

BCMA是除TACI外BAFF和APRIL共用的另一细胞表面受体。为了研究sBCMA作为拮抗受体的可能及获得活性sBCMA蛋白用做结构功能研究,我们以RTPCR法从人B系非洲淋巴瘤细胞株Raji总RNA中扩增出人BCMA的全长cDNA,经克隆测序证实所克隆的基因为人BCMA。继而通过嵌套PCR扩增出胞外可溶区(sBCMA,46个氨基酸组成,含有一个6个半胱氨酸的保守CRD,构成3个二硫键)cDNA,构建原核表达载体pET43.1a( )sBCMA,在大肠杆菌菌株OrigamiB(DE3)pLysS中高可溶性融合表达出重组蛋白sBCMANusAHis6,同时克隆表达了融合蛋白NusAHis6。经Ni NTA亲和纯化后的目的蛋白进行细胞学实验表明sBCMA能特异阻断BAFF促小鼠B细胞的增殖作用,而NusAHis6则不能,证实我们所表达得到的受体胞外可溶性片段sBCMA与配体具有较高的结合活性。sBCMA融合蛋白的成功表达将为二硫键富含类蛋白的表达提供参考,并为研究其临床应用以及BAFF和APRIL受体结构和功能的关系奠定基础。     

BAFF及相关疾病

BAFF是TNF超家族的一个新成员,属Ⅱ型跨膜蛋白,由285个氨基酸组成,通过与其受体结合而广泛参与B、T淋巴细胞增殖和功能的调节。BAFF缺乏可导致免疫功能低下,过表达则与多种自身免疫性疾病的发生和发展密切相关,BAFF可能还与某些肿瘤的发生有关。以BAFF及受体为作用靶点,可以设计治疗相关疾病的新策略。     

B淋巴细胞活化因子抗体在自身免疫性疾病治疗中的研究进展北大核心CSCD

近几十年来,自身免疫性疾病的治疗已从使用激素和常规免疫抑制药物转向使用生物制剂。B淋巴细胞的增殖及成熟对自身免疫性疾病的发病起到至关重要的作用。其中,肿瘤坏死因子超家族B淋巴细胞活化因子(B cell activating factor,BAFF)及其受体通过调控信号通路介导B淋巴细胞存活,因此BAFF及其受体是自身免疫性疾病的重要治疗靶点。文中阐述了BAFF及其受体在人体免疫系统中的作用机制,同时介绍了BAFF通路的过度活化如何促进系统性红斑狼疮、干燥综合征和类风湿关节炎等自身免疫疾病发展的最新观点。针对以上3种疾病,文中以3种主要的靶向BAFF抗体药物Belimumab、Tabalumab和Atacicept为例,介绍和讨论了其最新的临床试验及临床应用现状。最后提出靶向BAFF通路开发新型治疗自身免疫性疾病的方案和策略。     

甲氨蝶呤治疗急性淋巴细胞白血病的疗效及对患者BAFF、APRIL的影响

目的:探讨甲氨蝶呤治疗急性淋巴细胞白血病的疗效及对患者B淋巴细胞刺激因子(BAFF)、增殖诱导配体(APRIL)的影响。方法:选择2016年8月至2018年9月我院收治的急性淋巴细胞白血病患者50例进行研究,以随机数表法分为观察组(n=26)和对照组(n=24)。对照组给予化疗治疗,观察组采用甲氨蝶呤治疗。比较两组患者的临床疗效、BAFF、APRIL、CD4~+、CD8~+、CD4~+/CD8~+水平变化情况及不良反应发生情况。结果:治疗后,观察组总有效率84.62%显著高于对照58.33%,差异显著(P0.05);治疗前,两组BAFF、APRIL水平无显著差异(P0.05);治疗后,两组BAFF、APRIL水平均显著下降,且观察组低于对照组(P0.05);治疗前,两组T淋巴细胞亚群水平无显著差异(P0.05);治疗后,两组T淋巴细胞亚群水平均显著改善,且观察组CD4~+、CD4~+/CD8~+高于对照组,CD8~+低于对照组(P0.05);两组患者不良反应发生情况均无统计学意义(P0.05)。结论:在急性淋巴细胞白血病患者中应用甲氨蝶呤效果显著,可有效改善患者BAFF、APRIL水平。     

CD147在调节性T细胞中作用的研究进展

CD147是一种免疫球蛋白超家族,它与肿瘤侵袭和转染,类风湿性关节炎,病毒入侵,淋巴细胞的迁移和活化,老年痴呆症,疟原虫入侵等病理过程密切先关,已成为癌症等疾病的新型药物靶标分子。作为一个单次跨膜蛋白,CD147的多功能性依赖于它的胞外结构域以及细胞膜和细胞外多种分子的相互作用。有研究发现CD147可作为细胞膜受体并且在上皮细胞,肿瘤细胞和免疫T细胞中均有表达。其可作为T细胞亲环素受体并具有趋化T细胞的功能。近几年研究发现,CD147在调节性T细胞高表达并且具有标志性意义。该文就以作为活性调节性T细胞标志的CD147的潜在作用进展综述如下。     

质子感知受体与肿瘤发生和肿瘤转移之间的关系

G蛋白偶联受体家族卵巢癌G蛋白偶联受体1（ovarian cancer G protein-coupled receptor 1, OGR1）亚家族的OGR1、T细胞死亡偶联基因8（T－cell death associated gene 8, TDAG8）、G 蛋白偶联受体4（G protein－coupled receptor 4, GPR4）及诱导细胞停滞于G2/M期的G蛋白偶联受体G2A（from G2 accumulation）4 种受体是最新发现的一类质子感知受体.除了质子,体内又有它们各自特定的脂质分 子配体活化这些受体来调节细胞机能.该类受体广泛分布于人的各种正常组织和肿瘤 组织细胞中,在肿瘤的发生与转移、细胞骨架重组等生理病理过程中发挥双重作用. 正常表达时它们有一定的抑制肿瘤作用,但这些受体的异常表达或过表达使某些组织 和细胞恶性转化,导致肿瘤的发生.本文综述了在肿瘤组织的酸性微环境中,细胞表 达的质子（pH）感知受体对肿瘤发生与肿瘤转移的调节作用及其相关的信号通路.     

B细胞活化因子与类风湿性关节炎

B细胞活化因子具有刺激B细胞增殖和成熟的作用,过表达的B细胞活化因子与类风湿性关节炎等自身免疫疾病有着密切的关系,因此研究以B细胞活化因子为靶点治疗类风湿性关节炎具有一定的前景。本文对B细胞活化因子的表达、受体及其功能、BAFF在类风湿性关节炎发病机制中的作用、以B细胞活化因子为靶点治疗类风湿性关节炎等方面的研究现状及前景作综述。     

B7家族的新成员

T细胞的活化需要共刺激分子和其受体及特异性抗原与T细胞受体的双信号作用。B7家族成员是重要的共刺激分子,除B7－1和B7－2,新近又发现了一些新成员：B7RP－1（又名B7h,GL50或ICOSL）为鼠ICOS（inducible costimulator,CD28家族的第三位成员）的配体,其人的同源物命名为B7－2（也称为GL50或ICOSL）,它对TG细胞生长及细胞因子产生的共刺激作用已明显,B7－H1（也称PD－1L）,B7H3是一类不与ICOS结合的B7家族新成员。现已证实。现已证实,这些分子与其受体之间的作用在T细胞增殖及发挥效应中扮演重要角色,它们在许多疾病中的作用也引起学者的普遍关注。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.