胰高血糖素样肽-1保护胰岛β细胞相关分子机制的研究进展

胰高血糖素样肽-1(Glucagon-like peptide-1,GLP-1)是肠道L细胞分泌的一种重要的肠促胰岛素.大量研究表明,除刺激胰岛素分泌外,GLP-1可通过促进胰岛β细胞增殖,抑制β细胞凋亡而增加胰岛β细胞量,本文就其相关分子信号转导机制进行综述.     

免疫衰老与T、B细胞改变的相关研究

胸腺、适应性免疫系统的T、B细胞及固有免疫系统中中性粒细胞、巨噬细胞、NK/NKT细胞、树突状细胞等免疫细胞与免疫衰老（immunosenescence）均存在一定相关性。免疫衰老主要涉及适应性免疫系统的改变,本文将从T、B细胞的数目、功能、表面分子、分泌的细胞因子及其信号转导等方面的改变进行总结。     

胞吐参与植物生物胁迫应答的研究进展

高等植物细胞内囊泡运输介导了膜结构之间的物质运输和信号转导,其中,胞吐调控了运输囊泡向质膜的转运,参与了植物细胞壁形成、细胞分泌和环境响应等多种生物学过程。胞吐可以通过重构及强化细胞壁阻止病原体定殖、分泌抗微生物因子抵御病原体的入侵以及调控植物激素载体蛋白和受体蛋白的极性运输等参与抗病应答。遗传学证据表明胞吐是调控植物生物胁迫响应的重要机制。该文综述胞吐参与植物生物胁迫应答分子机制的研究进展,以期为本领域研究提供参考。     

拉特罗毒素的结构、受体及促分泌机制

α-拉特罗毒素(α-latrotoxin,α-LTX;也称:α-黑寡妇蜘蛛毒素)是一种从黑寡妇蜘蛛毒液中纯化到的,可以有效地触发神经元轴突终末神经递质的释放和分泌细胞分泌的神经毒素。它在细胞膜上存在三类受体。通过与其受体的结合,α-LTX可以通过对细胞膜的穿孔作用以及受体介导的跨膜信号转导两种方式触发细胞分泌。对α-LTX的促分泌作用机制的研究可以促进人们对分泌及其调节机制的深入认识。     

固有免疫细胞及其模式识别受体与表观遗传学调控研究进展

固有免疫细胞是机体抵御病原微生物的首道防线,亦是机体有效启动和维持免疫反应的重要参与者,而模式识别受体是固有免疫细胞发挥免疫功能的重要免疫分子,因此,机体对固有免疫细胞及其模式识别受体的精细调控尤为重要。表观遗传学是近年研究热点,其在固有免疫调节中的作用逐渐受到重视。就近年表观遗传学中的DNA甲基化、组蛋白共价修饰及非编码RNA等在调节固有免疫细胞分化发育及其模式识别受体的相关研究作一简述,以期为感染、炎症、自身免疫病等研究与防治提供新的思路和策略。     

胰岛素信号转导、昆虫发育与老化

胰岛素及其信号转导的探讨为当代生物学一大热点,研究显示:从线虫到果蝇、小鼠及其人类其胰岛素信号转导路径十分类似。昆虫胰岛素的研究开始于家蚕,在20世纪80年代,日本学者在分离家蚕促前胸腺激素(prothoracictropic hormone,简称PTTH)时,发现所纯化的为一称为家蚕素的神经激素,该激素之氨基酸排列顺序与高等动物体内的胰岛素部分相似,但是家蚕素的生理功能至今仍不是很清楚。而果蝇的分子遗传学研究则显示,胰岛素及其信号转导调控果蝇的生长、发育、寿命等许许多多的生理现象。专一性地改变果蝇前胸腺之胰岛素信号转导,会严重影响幼虫的蜕皮与变态。而作者利用家蚕所进行的研究更显示,将牛的胰岛素注射于家蚕幼虫体内可显着提高其蜕皮激素的分泌,离体培养前胸腺时加入牛胰岛素也可直接增加其激素的分泌,牛胰岛素可直接活化家蚕前胸腺细胞之胰岛素受体及信号分子Akt的磷酸化。另外,从线虫、果蝇到小鼠胰岛素及其信号转导突变体的研究结果显示了胰岛素信号转导调控寿命的重要性。利用猴子及人所进行的研究结果显示,低卡路里摄取之所以会延长寿命是因为卡路里的摄取与胰岛素信号转导的变化有关。因此,不同物种利用相同的胰岛素信号转导通路调控发育及老化机制,该发现大大鼓舞了科学家们利用低等的生物来研究复杂的生命现象。     

肿瘤微环境代谢对T细胞的影响

肿瘤微环境(tumor microenvironment,TME)包含肿瘤组织中各种细胞如肿瘤细胞、免疫细胞、成纤维细胞等,还包含这些细胞分泌的各种可溶性因子,以及代谢底物(如葡萄糖)和代谢产物(如乳酸)等等。由于肿瘤细胞和免疫细胞对营养共同的大量需求,肿瘤微环境中的肿瘤细胞和T细胞之间会发生营养代谢竞争。这种微环境中的营养竞争已经被证明和抗肿瘤免疫抑制的发生密切相关,但同时这种关联也是复杂的和多因素的。肿瘤微环境中的共抑制分子的表达、葡萄糖的竞争、氨基酸的竞争、氧的竞争以及乳酸的分泌等等,共同成为了免疫抑制表型的重要促进因素。这些研究也给肿瘤的治疗提供了新的方向。本文从肿瘤细胞和T细胞代谢重编程出发,介绍不同的微环境因素对T细胞的影响。     

肿瘤血管生成拟态形成的机制

血管生成拟态(vasculogenic mimicry,VM)主要是由肿瘤细胞形成的无内皮细胞的管样结构,主要为肿瘤在营养缺乏或侵袭过程中提供血液,与肿瘤的侵袭程度和患者预后相关。其形成的原因涉及多种复杂机制,包括肿瘤微环境诱导的调控蛋白、体内激素、RNA、肿瘤相关免疫细胞和肿瘤细胞的自分泌途径等。本文就近年关于肿瘤中各种分子机制促进VM形成做一简要综述。     

肝癌免疫逃逸机制的研究进展

肿瘤免疫逃逸在肝癌发生发展中起着重要作用。树突状细胞和免疫细胞的不成熟或功能低下将导致机体免疫功能被抑制而促进肝癌的发生发展。多种细胞因子如IL-10、TGF-β、VEGF等会抑制机体免疫功能使肝癌生长增殖或直接促进肿瘤的发生发展。肝癌细胞分泌Fas L及其表面Fas的表达减少会诱导免疫细胞凋亡或避免T细胞等免疫细胞的杀伤作用从而逃避机体免疫作用。因此,本文将从免疫细胞、肿瘤细胞本身以及两者间的相互作用三个方面阐述肝癌免疫逃逸的分子机制。     

白细胞介素—5及其受体的分子生物学进展

由于ＩＬ－５受体拮抗剂对哮喘等慢性过敏性疾病具有潜在的应用前景,近年对ＩＬ－５及其受体的分子生物学进行了细致深入的研究,本文就ＩＬ－５及其受体的基因结构和分子特性,二者作用的分子机制及其信号转导方面的研究作一综述。     

Maintenance of primary cell cultures of immunocytes from Cacopsylla spp. psyllids: a new in vitro tool for the study of crop pest insects

Primary cell cultures of immunocytes have been developed from the three psyllid species Cacopsylla melanoneura, Cacopsylla pyri (vectors of ‘Candidatus Phytoplasma mali’ and ‘Candidatus Phytoplasma pyri’, respectively) and Cacopsylla crataegi. The medium most suitable of those evaluated was Hert-Hunter 70 (HH70) psyllid medium. In fact, good survival and proliferation of the Cacopsylla immunocytes for over 60 d were observed, with mitosis activities starting at 15-d post culture. Moreover, adhesion and phagocytosis activities were confirmed for all the psyllid cell cultures by functionality tests. Morphological examination of cultured immunocytes revealed the presence of different cell types in all the three psyllid species in accordance to published data about insect immunocytes. The in vitro maintenance of psyllid immunocytes represents a powerful tool for a wide range of applications, especially for psyllid cell biology. In particular, in-depth studies on the biology of psyllids as vector insects as well as analyses to understand the mechanisms behind the interactions with pathogens and symbionts are now possible. These cultures can be used as an in vitro model to study psyllid humoral immune responses, which also will allow in-depth investigations on the abilities of psyllids as vectors of phytoplasmas. All these applications provide new opportunities to develop more focused and specific pest control strategies.     

Algal toxin yessotoxin signalling pathways involve immunocyte mussel calcium channels

A fragment of a putative L-type Ca(2+) channel has been identified by molecular biology experiments in immunocytes from the mussel Mytilus galloprovincialis. Using the cell permeable and Ca(2+)-specific fluorochrome FURA 2-AM, we have demonstrated that the algal toxin yessotoxin (YTX) is able to increase intracellular Ca(2+) concentration in M. galloprovincialis immunocytes. The YTX effect on Ca(2+) increase is inhibited by the L-type Ca(2+) channel inhibitor, verapamil, which is cAMP- and cGMP-dependent, but PKA- and nitric oxide-independent. On the basis of these observations, a possible role for YTX as a potential disturber of mussel immune efficiency is suggested.     

基于合成基因线路的智能药物

合成生物学自诞生以来对生物学领域的研究产生了重要的影响。利用工程学思维与方法,合成生物学揭开了生命系统许多调控机制,改造并扩展了一系列生物元件,同时带来了广泛的生物医学应用,为疾病诊断与治疗提供了新的思路。本文综述了适用于哺乳动物细胞或者细菌的合成基因线路并用于疾病诊断与治疗领域的最新进展,为未来智能药物设计提供新的思路。     

Systems and synthetic biology approaches to cell division

Cells proliferate by division into similar daughter cells, a process that lies at the heart of cell biology. Extensive research on cell division has led to the identification of the many components and control elements of the molecular machinery underlying cellular division. Here we provide a brief review of prokaryotic and eukaryotic cell division and emphasize how new approaches such as systems and synthetic biology can provide valuable new insight.     

Isolation of suppressor T lymphocytes adherent to histamine conjugated albumin and their role in suppression of IgG response to SRBC

Antigen-specific immunosuppression to sheep red blood cells (SRBC) in BALB/c mice was induced by repetitive injection of high doses of soluble components derived from a hypotonic lysis of SRBC. This form of unresponsiveness induced both IgM and IgG suppression. The IgG, but not the IgM suppression, was stable and persisted in an adoptive transfer. The transferred IgG unresposiveness could be terminated by the removal of a cell population that bound to histamine-rabbit serum albumin-Sepharose (HRS). Such a population could actively suppress normal immunocytes as well as immunocytes in which suppression was eliminated by removal of cells adherent to HRS. The suppressor population shows immunospecificity typical of T cells and its suppressive activity is completely abrogated by anti-θ antibody-induced lysis. Furthermore, we demonstrated that the cell, by virtue of separation on insolubilized histamine columns, has surface characteristics different from the helper T memory cell. Functional B and T immunocytes were found in the SRBC-suppressed mice. We therefore conclude that this type of antigen-induced immunosuppression is maintained solely through an active T cell-mediated suppression.     

合成生物学技术在环境保护中的应用

合成生物学是一个基于生物学和工程学原理的科学领域,其目的是重新设计和重组微生物,以优化或创建具有增强功能的新生物系统。该领域利用分子工具、系统生物学和遗传框架的重编程,从而构建合成途径以获得具有替代功能的微生物。传统上,合成生物学方法通常旨在开发具有成本效益的微生物细胞工厂进而从可再生资源中生产化学物质。然而,近年来合成生物学技术开始在环境保护中发挥着更直接的作用。本综述介绍了基因工程中的合成生物学工具,讨论了基于基因工程的微生物修复策略,强调了合成生物学技术可以通过响应特定污染物进行生物修复来保护环境。其中,规律间隔成簇短回文重复序列(Clustered Regularly Interspersed Short Palindromic Repeats, CRISPR)技术在基因工程细菌和古细菌的生物修复中得到了广泛应用,生物修复领域也出现了很多新的先进技术,包括生物膜工程、人工微生物群落的构建、基因驱动、酶和蛋白质工程等。有了这些新的技术和工具,生物修复将成为当今最好和最有效的污染物去除方式之一。     

Anchored cell analysis and sorting (ACAS) system]

Advanced biology and recent technology have provided sophisticated and objective method for analyzing biological characteristics on cells. Following that, many new instruments have developed. Diagnostic immunocytochemistry has become an accepted diagnostic tool in cell biology. In recent years, remarkable advances in technology provide a method for quantitative and objective analyses of cell characteristics. The newly developed computer assisted laser cytometer (ACAS 570) can be applied in clinical basis as well as in research laboratory. Fluorescent intensities of ancharage-dependent cells can be automatically analyzed and make it possible to separate a subpopulation of cells. This computer controlled system principally consists of argon ion laser, phase contrast microscope. Quantitative fluorescence measurements and computer graphic images can be obtained. The present paper demonstrates multiple applications of laser cytometer for evaluation of cell biology.     

Requirement of the Fas ligand-expressing luteal immune cells for regression of corpus luteum

Apoptosis in corpus luteum (CL) is induced by prolactin (PRL) in female rats. PRL-induced apoptosis in CL is mediated by the Fas/Fas ligand (FasL) system. The CL consists of steroidogenic and non-steroidogenic cells, including immunocytes. Fas mRNA was detected only in the luteal steroidogenic cells, and FasL mRNA was expressed only by the non-steroidogenic CD3-positive luteal immunocytes. Removing the luteal immune cells from the luteal cells inhibited PRL-induced luteal cell apoptosis effectively. Thus, FasL-expressing non-steroidogenic luteal immunocytes are required for PRL-induced luteal cell apoptosis and heterogeneous induction of apoptosis by Fas/FasL in CL.     

解析2009年度诺贝尔生理学或医学奖——端粒与端粒酶

美国加州大学旧金山分校的伊丽莎白·布莱克本（Elizabeth H. Blackburn）、约翰·霍普金斯医学院的卡罗尔·格雷德（Carol W. Greider）和马萨诸塞州总医院的杰克·绍斯塔克（Jack W. Szostak）,因为“发现端粒和端粒酶如何保护染色体”,而获得2009年度诺贝尔奖生理学或医学奖。这个结果已在很多人的意料之中。因为端粒和端粒酶的发现揭示了线性染色体末端复制的机制,以及端粒和端粒酶在保护染色体及维持遗传稳定性中的中心作用。端粒和端粒酶的发现为科学家认识并探索衰老和肿瘤的发生机制开辟了新领域,对预防和治疗衰老及与衰老相关的疾病（如肿瘤）具有重要科学和应用意义。     

Cloning Expeditions: Risky but Rewarding

In the 1980s, a good part of my laboratory was using the then-new recombinant DNA techniques to clone and characterize many important cell surface membrane proteins: GLUT1 (the red cell glucose transporter) and then GLUT2 and GLUT4, the red cell anion exchange protein (Band 3), asialoglycoprotein receptor subunits, sucrase-isomaltase, the erythropoietin receptor, and two of the subunits of the transforming growth factor β (TGF-β) receptor. These cloned genes opened many new fields of basic research, including membrane insertion and trafficking of transmembrane proteins, signal transduction by many members of the cytokine and TGF-β families of receptors, and the cellular physiology of glucose and anion transport. They also led to many insights into the molecular biology of several cancers, hematopoietic disorders, and diabetes. This work was done by an exceptional group of postdocs and students who took exceptionally large risks in developing and using novel cloning technologies. Unsurprisingly, all have gone on to become leaders in the fields of molecular cell biology and molecular medicine.