内毒素耐受机制的研究进展

内毒素耐受（endotoxin tolerance）早在50多年前就已经引起人们的关注,但其具体的分子机制至今尚不清楚。Toll样受体4（Toll-1ike receptor-4,TLR4）作为脂多糖（LPS）的主要受体,参与LPS信号的跨膜转导,与LPS耐受密切相关。在内毒素耐受过程中,TLR4转导通路中的信号蛋白及下游转录因子在数量、结构和功能上发生改变,可引起炎性因子释放减少、抗炎因子产生增加,并导致特定信号通路（如P13K通路）和负性调节因子（如SHIP1、SOCS、FLN29等）的激活。除此之外,TLR2通路、Gi蛋白、蛋白激酶C（protein kinase C,PKC）以及一些信号分子的剪接异构体等也参与了内毒素耐受现象的发生。总之,内毒素耐受是一个由多种原因引起的、多种生物物质参与的复杂病理生理过程,是机体抵抗G-细菌感染的重要保护机制。因此,探索内毒素耐受的机制,寻求机体内源性的抗炎机制将为败血症等一些致死性感染性疾病的治疗提供新的思路和理论依据。     

Toll样受体通路调节Tregs功能的研究进展

模式识别受体Toll样受体(Toll like receptors,TLRs)是固有免疫中免疫受体的代表,进化上十分保守,对生物体的生存极为重要。TLRs通过内源或外源的配体启动信号转导,激活下游一系列重要的基因表达与活化。研究表明调节性T细胞(Regulatory T cell,Treg)在维持机体外周免疫耐受和阻止移植排斥反应等方面发挥核心作用。Treg细胞表达某些TLRs,包括TLR2、TLR4、TLR5、TLR7、TLR8、TLR9等。TLRs的活化可能直接或间接地影响(主要是活化) Treg的增殖和免疫抑制功能,这种调节与感染、自身免疫病和癌症的发生密切相关。其中热休克蛋白作为TLRs配体分子对于Treg的调节发挥了重要的作用。因此,了解TLRs通路对研究Treg免疫调控机制、新药物研发和靶向治疗有重大意义。文中简要介绍了TLRs通路调节Treg免疫功能的相关研究进展。     

微生物未甲基化CpG DNA对动物肠道的免疫调节作用

摘要:微生物未甲基化CpG DNA为富含未甲基化胞嘧啶-鸟嘌呤二核苷酸的DNA片段,能够被动物肠道细胞Toll样受体家族中的TLＲ9 受体(Toll-like receptor 9,TLR9)特异性识别。未甲基化CpG DNA作为一种动物肠道免疫刺激因子,不仅能够直接调节肠道固有免疫应答,同时还能间接介导肠道适应性免疫应答。未甲基化CpG DNA具有调节机体免疫应答作用的应用前景,成为免疫佐剂开发的研究热点。本文主要综述微生物未甲基化CpG DNA基本概念、受体TLR9的特征、调节动物肠道免疫作用及其信号机制,同时阐述了未甲基化CpG DNA作为免疫佐剂在实际中的应用,最后对微生物未甲基化CpG DNA研究与开发利用前景进行了展望。     

泛素化修饰调控固有免疫信号通路的研究进展

宿主细胞依赖固有免疫系统识别入侵的病原微生物,经相关细胞信号转导通路,激活促炎症及抗感染的基因表达。泛素化修饰是细胞内广泛存在的蛋白质翻译后修饰机制,全方位调控宿主细胞防御病原微生物的动态过程:一方面,作为多功能的信号调节分子,在时空上精细调节免疫反应的进程,有效地清除入侵的病原体;另一方面,通过降解关键信号转导分子,限制过度免疫反应,避免造成宿主自体损伤。本文总结了泛素化修饰在Toll样受体信号通路(TLR)、RIG-I样受体信号通路(RLR)和STING介导的信号通路中的新功能,以及相关分子调控机制,并对前沿方向进行展望。     

DNA疫苗抗原提呈的传感器分子研究新进展

DNA疫苗进入细胞后,除了转译成蛋白质抗原,通过MHC分子进行内源性或外源性抗原提呈外,近年来还发现可直接与相应的被称为核酸传感器分子,如TLR9、DAI、AIM2、STING、DDX41解旋酶和RNA聚合酶Ⅲ等结合,继而激活不同的免疫信号通路.基于DNA疫苗的传感器分子和信号通路研制免疫佐剂,可有效增强DNA疫苗的免疫原性.     

TLR/MyD88信号通路与自身免疫性疾病

Toll样受体(Toll-like receptor,TLR)是近年来发现的一类模式识别受体,通过识别病原相关分子模式(pathogen-associated molecular pattern,PAMP),激活天然免疫.TLR信号还通过上调抗原提呈细胞(antigen presenting cells,APC)表面共刺激分子及APC分泌的炎症细胞因子调节获得性免疫.TLR/MyD88信号在自身免疫性疾病的发病过程中起重要作用.本文介绍了TLR/MYD88信号通路及其在自身免疫病如实验性自身免疫脑脊髓膜炎、类风湿性关节炎、实验性自身免疫性葡萄膜炎、实验性自身免疫性心肌炎和自身免疫性肾小球肾炎等发生发展中的作用.     

5-羟色胺与Toll样受体及肠道菌群之间关系的研究

5-羟色胺(5-HT)是参与调节胃肠道运动、内脏敏感性、分泌等功能的重要神经递质和信号分子。肠道菌群对5-HT的产生有重要影响,已发现一些产芽孢细菌(spore-forming bacteria,SP)类肠道微生物能刺激肠嗜铬细胞(enterochromaffin cell,EC)产生5-HT。微生物通过Toll样受体(Toll-like receptors,TLR)激活神经分泌机制来调节胃肠运动,某些TLR通过作用于5-HT受体调节小鼠回肠的自主收缩和5-HT诱导的收缩反应。通过调节肠道菌群可以对5-HT综合征及其相关生理和病理状况产生重要影响。因此,对5-HT与TLR及肠道菌群相互之间的关系进行进一步的研究有重要意义。     

DAI做为DNA传感器可以激活固有免疫反应

固有免疫的中心环节是细胞质和细胞膜相关的受体对病原体相关分子的感知。感染或组织损伤过程中,DNA是强效的免疫反应激活物。以往的研究结果显示除了细胞膜相关的Toll样受体9(Toll-like receptor9,TLR9)外,一种尚未被鉴定的细胞质DNA传感器同样可以激活1型干扰素(IFN)并引起其     

CpG DNA特异性识别的关键蛋白Toll样受体-9

Toll样受体在对抗外来病原微生物的天然免疫应答中发挥中心作用。新发现的一种分子识别模型受体Toll样受体-9（TLR9）,能特异性识别CpG DNA并起动信号转导级联反应,在不同种类中的TLR9具有对序列识别的特异性。本文概述国外在TLR9识别作用机制和生物学活性研究中已取得的进展,并提出了今后研究的发展方向。     

TLR9的生物学特性及其在心血管疾病中的研究进展

Toll样受体(toll-like receptors,TLRs)是一类保守的介导固有免疫的跨膜信号传递受体家族,是一种I型跨膜蛋白受体,是模式识别受体(pattern recognition receptor,PRR)中的一员,在识别和抵御各种病原微生物及其产物的过程中发挥重要作用。病原微生物呈现多种真核细胞不具备的特殊的保守结构,称为病原相关分子模式(pathogen associated molecular patterns,PAMPs),这种结构可被PRR所识别,并通过下游的接头蛋白引发转录因子的激活和炎症因子的产生。不同的TLR分子具有各自特异的PAMPs识别谱,其中Toll样受体9(TLR9)是识别细菌来源的非甲基化CpG DNA等PAMPs的受体。TLRs在固有免疫和适应性免疫中发挥着重要作用,并参与多种心血管疾病的发病过程。本文就TLR9的生物学特性及其在心血管疾病中的研究进展进行综述。     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Entwicklungsgeschichte und Ultrastruktur von Pollenkitt und Exine bei nahe verwandten entomophilen und anemophilen Angiospermensippen derAlismataceae,Liliaceae, Juncaceae,Cyperaceae, Poaceae undAraceae

Some closely related members of the monocotyledonous familiesAlismataceae, Liliaceae, Juncaceae, Cyperaceae, Poaceae andAraceae with variable modes of pollination (insect- and wind-pollination) were studied in relation to the ultrastructure of pollenkitt and exine (amount, consistency and distribution of pollenkitt on the surface of pollen grains). The character syndromes of pollen cementing in entomophilous, anemophilous and intermediate (ambophilous or amphiphilous) monocotyledons are the same in principal as in dicotyledons. Comparing present with former results one can summarize: 1) The pollenkitt is always produced in the same manner by the anther tapetum in all angiosperm sub-classes. 2) The variable stickiness of entomophilous and anemophilous pollen always depends on the particular distribution and consistency of the pollenkitt, but not its amount on the pollen surface. 3) The mostly dry and powdery pollen of anemophilous plants always contains a variable amount of inactive pollenkitt in its exine cavities. 4) A step-by step change of the pollen cementing syndrome can be observed from entomophily towards anemophily. 5) From the omnipresence of pollenkitt in all wind-pollinated angiosperms studied one can conclude that the ancestors of anemophilous angiosperms probably have been zoophilous (i.e. entomophilous) throughout.

     

Identification and Characterization of the First Equine Parainfluenza Virus 5

正Dear Editor,Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative-sense,nonsegmented, single-stranded RNA virus belonging to the Paramyxoviridae family (Chen 2018). The virus was first reported in primary monkey kidney cells in 1954 (Hsiung1972), then it has been frequently discovered in various