细胞因子TNFSF13B的结构与功能及其在相关疾病发生中的作用

TNFSF13B是于1999年发现并克隆的一种重要的细胞因子,它广泛参与了T、B淋巴细胞的增殖及功能调节。该介绍TNFSF13B的结构及功能特点、TNFSF1B在相关疾病(如免疫功能低下、某些自身免疫性疾病及某些肿瘤等)发生中的作用以及TNFSF13B在相关疾病治疗中的应用前景等。     

TNF家族成员TALL-1及其研究进展

TALL-1是TNF家族成员中最近发现的一个新型细胞因子,由单核细胞和巨噬细胞产生. 人TALL-1由285个氨基酸残基组成,而鼠TALL-1由309个氨基酸残基构成,两者均为Ⅱ型穿膜蛋白质. 人sTALL-1是长为152个氨基酸残基的胞外区片段,对应于C端134～285位氨基酸残基. 重组人sTALL-1具有刺激B细胞增殖、激活NF-κB和JNK以及抑制肿瘤细胞生长等生物学活性. 另外,TALL-1在转基因鼠中的过量表达可引起严重的B细胞增生以及与狼疮有关的自身免疫性疾病. 因此,TALL-1是一个具有多种生物学活性的细胞调控因子.     

人细胞毒性T淋巴细胞TALL-104抗癌细胞活性的检测

检测人细胞毒性T淋巴细胞TALL-104对癌细胞的杀伤活性以及此杀伤活性对白细胞介素-2的依赖性,动态观察其体外增殖能力.用台盼兰拒染法计算细胞扩增倍数;用MTT法检测细胞毒杀伤活性,实时观察细胞的杀伤过程.结果表明, 在200 IU/ml IL-2刺激下,TALL-104细胞增殖能力较强;在效靶比5∶ 1,作用时间为24 h,TALL-104细胞表现出对癌细胞MCF-7和A-431较高的杀伤率分别为50.4%和69.5%;当作用时间在72 h以内,效靶比不高于10∶ 1时,杀伤率随作用时间和效靶比的增加而明显升高(P<0.05);最大杀伤率分别为79.8%(MCF-7细胞)和90.4%(A431细胞).因此,TALL-104细胞体外增殖能力较强,其细胞毒活性不严格依赖于IL-2的存在.     

GC7在炎症及缺氧缺血性相关疾病中的作用

临床上,炎症和缺氧缺血与大多数疾病的病情严重程度及预后等密切相关。真核翻译起始因子5A(eukaryotic translation initiation factor 5A, EIF5A)在线粒体代谢功能的调节及促炎因子的释放中发挥重要作用,影响炎症及缺氧缺血的发生发展。N1-甲眯基-1,7-二氨基庚烷GC7(N1-guany1-1,7-diaminohep-tane)是EIF5A活化中的关键酶[脱氧羧腐胺赖氨酸合酶DHS(deoxyhypusinesynthase)]的抑制剂,可以通过抑制EIF5A的活性,进一步稳定线粒体功能,预防有毒活性氧(reactive oxygen species,ROS)的生成,减少炎症因子的释放,从而改善脑卒中、肾移植、肾缺血等缺氧缺血相关疾病和炎症相关疾病的症状。所以,GC7有望成为临床上治疗炎症和缺氧缺血相关疾病的不错选择。本文对GC7在炎症和缺氧缺血相关疾病中的作用及机制进行综述。     

溶酶体途径在细胞自噬过程中的功能意义

溶酶体具有高度保守的异质性,是细胞自噬的关键细胞器。细胞质中的蛋白质和细胞器最终在溶酶体降解,故溶酶体在维持细胞结构和功能的平衡方面起着重要生理作用。通过自噬溶酶体途径,细胞可清除某些病原体并参与抗原呈递。细胞自噬与异噬经溶酶体密切联系。自噬过程中溶酶体功能障碍与某些疾病和衰老等相关。对细胞自噬的溶酶体途径及其功能意义作了概述。     

雄激素及其受体在肥胖、肥胖相关疾病及糖脂代谢紊乱中的作用

雄激素在肥胖及肥胖相关疾病如糖尿病、代谢综合征、动脉粥样硬化、高血压、心血管疾病等的发生及肥胖的糖脂代谢紊乱中的作用受到越来越多的关注。雄激素的作用主要通过雄激素受体(androgen receptor,AR)介导,AR属于核受体超家族成员,在骨骼肌、肝脏、脂肪、脑等组织中均有分布和表达。低水平的睾酮和AR功能缺失能促进肥胖及其相关疾病的发生,诱导糖脂代谢的紊乱。睾酮/AR能调控几乎所有与糖脂代谢、肥胖相关疾病发生有关的途径,包括糖脂代谢关键酶和关键蛋白、核转录因子(PPARγ、LXRα、FoxO1)、炎症反应、下丘脑的瘦素敏感性、脂肪细胞的增殖和分化、线粒体功能和血管内皮细胞功能。此外,与男性不同,高水平雄激素的女性可出现肥胖及糖脂代谢的紊乱,其机制还不清楚。本文主要就雄激素和AR在男性肥胖及其相关疾病的发生以及糖脂代谢紊乱中的作用及机制作一综述。     

SUMO化修饰在核受体功能调控中的作用

小泛素相关修饰蛋白(small ubiquitin related modifier,SUMO)修饰作用是蛋白质翻译后修饰的重要方式。SUMO化修饰与泛素化作用极为相似,并且在某些靶蛋白上可以与泛素竞争结合位点,从而起到稳定靶蛋白的作用,并参与调节靶蛋白的细胞定位、膜离子通道功能、DNA损伤修复以及转录活性等。核受体是一类在生物体内广泛分布的、配体依赖的转录因子超家族,参与机体生长发育、细胞分化,以及体内许多生理、病理过程中的基因表达调控。最近研究发现,核受体的SU-MO修饰可通过影响核受体的稳定性、转录活性、亚细胞定位等多重途径影响核受体的功能,并影响机体炎症反应及相关疾病的发生发展。本文对核受体的SUMO修饰在核受体功能调控中的作用,以及与机体相关疾病之间的关系做一简要综述。     

FKBP52功能及与疾病联系的研究进展

FKBP52为FK506结合蛋白(FKBPs)家族的一个亚类,其包括FK1、FK2、TRP区在内的三个结构区。其中,FK1区的FK506结合位点具有可调控靶蛋白的PPIase活性,而TRP区可为Hsp90提供结合位点。FKBP52的主要功能在于对甾体激素受体信号通路的调节,如受体的结合、转运等,同时在调控神经元微管功能中也发挥重要作用。最近研究发现,FKBP52与多种癌症、生殖疾病及某些中枢神经系统相关疾病的发生存在一定联系。本文主要对FKBP52目前已知的生物学功能及与疾病的关联进行综述,同时对其应用前景进行展望,以期为FKBP52的进一步研究提供参考。     

肾上腺素能受体信号调控巨噬细胞参与疾病微环境的研究进展

肾上腺素能受体(adrenergic receptors, ARs)作为神经系统功能调控的关键受体之一,在多种疾病的免疫微环境形成以及疾病进展中扮演重要角色。近年来ARs及其信号对巨噬细胞功能的调控成为研究热点。在不同疾病微环境中,ARs通过对巨噬细胞的分化与发育发挥不同的调节功能,进而影响肿瘤、肥胖、急性损伤与感染性疾病、心力衰竭以及妊娠相关疾病的发生和发展。本文从ARs的分型及激活途径,ARs在巨噬细胞的表达、功能调控及在不同疾病微环境中的作用等方面进行综述,以期为相关疾病的干预和治疗提供新思路。     

线粒体融合与分裂在中枢神经系统疾病中的研究进展

线粒体是一种高度动态的细胞器,通过不断的融合和分裂维持其动态平衡,参与生理病理功能调节。线粒体融合与分裂主要由融合分裂相关蛋白调控,如Drp1、Fis1、Mfn1、Mfn2、OPA1等,多种诱导因子通过调节线粒体融合分裂相关蛋白表达及活化进而调节线粒体形态和生理功能。现有研究表明线粒体融合分裂的异常可能是许多中枢神经系统疾病的发病机制之一。本文从线粒体融合分裂的分子调控机制及其在缺血性脑中风、帕金森综合征和阿尔兹海默症等中枢神经系统疾病中的研究进展方面进行综述,为相关疾病的防治提供一定参考和线索。     

On the origin of the Hirudinea and the demise of the Oligochaeta

The phylogenetic relationships of the Clitellata were investigated with a data set of published and new complete 18S rRNA gene sequences of 51 species representing 41 families. Sequences were aligned on the basis of a secondary structure model and analysed with maximum parsimony and maximum likelihood. In contrast to the latter method, parsimony did not recover the monophyly of Clitellata. However, a close scrutiny of the data suggested a spurious attraction between some polychaetes and clitellates. As a rule, molecular trees are closely aligned with morphology-based phylogenies. Acanthobdellida and Euhirudinea were reconciled in their traditional Hirudinea clade and were included in the Oligochaeta with the Branchiobdellida via the Lumbriculidae as a possible link between the two assemblages. While the 18S gene yielded a meaningful historical signal for determining relationships within clitellates, the exact position of Hirudinea and Branchiobdellida within oligochaetes remained unresolved. The lack of phylogenetic signal is interpreted as evidence for a rapid radiation of these taxa. The placement of Clitellata within the Polychaeta remained unresolved. The biological reality of polytomies within annelids is suggested and supports the hypothesis of an extremely ancient radiation of polychaetes and emergence of clitellates.     

On the ontogeny of the haptor and the evolution of the Monogenea

Data on the ontogeny of the posterior haptor of monogeneans were obtained from more than 150 publications and summarised. These data were plotted into diagrams showing evolutionary capacity levels based on the theory of a progressive evolution of marginal hooks, anchors and other attachment components of the posterior haptor in the Monogenea (Malmberg, 1986). 5 + 5 unhinged marginal hooks are assumed to be the most primitive monogenean haptoral condition. Thus the diagrams were founded on a 5 + 5 unhinged marginal hook evolutionary capacity level, and the evolutionary capacity levels of anchors and other haptoral attachement components were arranged according to haptoral ontogenetical sequences. In the final plotting diagram data on hosts, type of spermatozoa, oncomiracidial ciliation, sensilla pattern and protonephridial systems were also included. In this way a number of correlations were revealed. Thus, for example, the number of 5 + 5 marginal hooks correlates with the most primitive monogenean type of spermatozoon and with few sensillae, many ciliated cells and a simple protonephridial system in the oncomiracidium. On the basis of the reviewed data it is concluded that the ancient monogeneans with 5 + 5 unhinged marginal hooks were divided into two main lines, one retaining unhinged marginal hooks and the other evolving hinged marginal hooks. Both main lines have recent representatives at different marginal hook evolutionary capacity levels, i.e. monogeneans retaining a haptor with only marginal hooks. For the main line with hinged marginal hooks the name Articulon-choinea n. subclass is proposed. Members with 8 + 8 hinged marginal hooks only are here called Proanchorea n. superord. Monogeneans with unhinged marginal hooks only are here called Ananchorea n. superord. and three new families are erected for its recent members: Anonchohapteridae n. fam., Acolpentronidae n. fam. and Anacanthoridae n. fam. (with 7 + 7, 8 + 8 and 9 + 9 unhinged marginal hooks, respectively). Except for the families of Articulonchoinea (e.g. Acanthocotylidae, Gyrodactylidae, Tetraonchoididae) Bychowsky's (1957) division of the Monogenea into the Oligonchoinea and Polyonchoinea fits the proposed scheme, i.e. monogeneans with unhinged marginal hooks form one old group, the Oligonchoinea, which have 5 + 5 unhinged marginal hooks, and the other group form the Polyonchoinea, which (with the exception of the Hexabothriidae) has a greater number (7 + 7, 8 + 8 or 9 + 9) of unhinged marginal hooks. It is proposed that both these names, Oligonchoinea (sensu mihi) and Polyonchoinea (sensu mihi), will be retained on one side and Articulonchoinea placed on the other side, which reflects the early monogenean evolution. Except for the members of Ananchorea [Polyonchoinea], all members of the Oligonchoinea and Polyonchoinea have anchors, which imply that they are further evolved, i.e. have passed the 5 + 5 marginal hook evolutionary capacity level (Malmberg, 1986). There are two main types of anchors in the Monogenea: haptoral anchors, with anlages appearing in the haptor, and peduncular anchors, with anlages in the peduncle. There are two types of haptoral anchors: peripheral haptoral anchors, ontogenetically the oldest, and central haptoral anchors. Peduncular anchors, in turn, are ontogenetically younger than peripheral haptoral anchors. There may be two pairs of peduncular anchors: medial peduncular anchors, ontogentically the oldest, and lateral peduncular anchors. Only peduncular (not haptoral) anchors have anchor bars. Monogeneans with haptoral anchors are here called Mediohaptanchorea n. superord. and Laterohaptanchorea n. superord. or haptanchoreans. All oligonchoineans and the oldest polyonchoineans are haptanchoreans. Certain members of Calceostomatidae [Polyonchoinea] are the only monogeneans with both (peripheral) haptoral and peduncular anchors (one pair). These monogeneans are here called Mixanchorea n. superord. Polyonchoineans with peduncular anchors and unhinged marginal hooks are here called the Pedunculanchorea n. superord. The most primitive pedunculanchoreans have only one pair of peduncular anchors with an anchor bar, while the most advanced have both medial and lateral peduncular anchors; each pair having an anchor bar. Certain families of the Articulonchoinea, the Anchorea n. superord., also have peduncular anchors (parallel evolution): only one family, the Sundanonchidae n. fam., has both medial and lateral peduncular anchors, each anchor pair with an anchor bar. Evolutionary lines from different monogenean evolutionary capacity levels are discussed and a new system of classification for the Monogenea is proposed.In agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. EditorIn agreeing to publish this article, I recognise that its contents are controversial and contrary to generally accepted views on monogenean systematics and evolution. I have anticipated a reaction to the article by inviting senior workers in the field to comment upon it: their views will be reported in a future issue of this journal. Editor