长链非编码RNAs与心脏发育及心血管系统相关疾病的关系

长链非编码RNAs(lncRNAs)是生物体内转录本长度超过200 nt的RNA分子,它们并不编码蛋白,但参与了X染色体沉默,基因组印记以及染色质修饰,转录激活,转录干扰以及核内运输等多种重要的调控过程。近年研究表明,lncRNAs与心脏发育及心血管系统相关疾病密切相关,一些特异的lncRNAs有可能为心血管系统相关疾病的诊断和治疗提供新的靶点和研发新的药物。     

长链非编码RNAs与心脏发育及心血管系统相关疾病的关系

长链非编码RNAs（1ncRNAs）是生物体内转录本长度超过200nt的RNA分子,它们并不编码蛋白,但参与了X染色体沉默,基因组印记以及染色质修饰,转录激活,转录干扰以及核内运输等多种重要的调控过程。近年研究表明,lncRNAs与心脏发育及心血管系统相关疾病密切相关,一些特异的lncRNAs有可能为心血管系统相关疾病的诊断和治疗提供新的靶点和研发新的药物。     

线粒体抗病毒信号蛋白与RNA病毒的相互作用

天然免疫是宿主细胞在生物进化过程中形成的抵御外来侵袭的第一道防线。病毒感染后通过信号转导机制引发机体免疫反应,线粒体抗病毒信号蛋白(MAVS)作为天然免疫信号通路的重要接头蛋白,可以接收上游Toll样受体(TLR)和维甲酸诱导基因I(RIG-I)受体(RLRs)等识别RNA病毒并传递信号,活化下游NF-κB和IRF3/7相关信号通路,从而激活干扰素表达,介导天然免疫相关信号通路。RNA病毒在长期进化过程中针对MAVS也形成了一系列免疫逃逸策略。本综述介绍了MAVS的发现及结构,并对MAVS抗RNA病毒的作用及病毒对MAVS的负调控进行综述,旨在为相关研究提供帮助。     

长链非编码RNA在心肌重构中的研究进展

心肌重构是机体应对心室压力负荷增高或神经体液激素及细胞因子等各种因素刺激时的一种代偿反应,主要表现为心肌肥厚、心肌纤维增多、心肌细胞凋亡,经失代偿至心肌扩张,最终发展成为心力衰竭。长链非编码RNA(long non-coding RNAs,lncRNAs)是一类长度大于200个核苷酸且不编码蛋白质的转录本。研究表明,lncRNAs参与调控心肌肥厚、心肌纤维化和心肌细胞凋亡等心肌重构过程。经报道发现lnc RNA Chaer、Chast、Mhrt、CHRF、H19和MIAT在心肌肥厚的发生发展过程中有重要作用;MEG3、H19、GAS5参与调控心肌纤维化发生与发展;MHRT、UCA1、CARL与心肌细胞凋亡有密切关系。因此通过调控lncRNAs的表达,有可能在一定程度上改善心肌重构以及某些心血管疾病进程。本文就将对lncRNAs做简单概述,对lncRNAs在心肌重构的研究进展进行综述。     

疱疹病毒US10基因及其编码蛋白研究进展

疱疹病毒US10基因位于其基因组的短独特区,是病毒复制的非必需基因,编码病毒的磷酸化衣壳-皮层蛋白或I型跨膜糖蛋白,可通过特异性识别非经典MHC I型分子的HLA-G胞质尾区,来下调HLA-G的表达量并阻断宿主NK细胞对病毒的杀伤,从而参与病毒的免疫逃逸;该蛋白通过与宿主蛋白相互作用而发挥致病作用,也能调节其它病毒蛋白如糖蛋白E(gE)等的表达。对US10结合RNA的能力及在病毒转录后调控、病毒毒力中的作用有待于深入研究。     

长链非编码RNAs在动脉粥样硬化血管功能调控中的作用机制

动脉粥样硬化是一种脂质诱导的慢性血管壁炎症反应,是血管为应对血脂异常和血流动力学应激(涉及血管细胞激活、功能障碍以及白细胞浸润)而产生的一种病理现象。作为一类细胞周期和细胞凋亡中的重要调控分子,长链非编码RNAs(Long noncoding RNAs,lncRNAs)在表观遗传调控、转录调控和转录后调控等多个阶段干扰基因表达或信号通路。越来越多的研究表明,IncRNAs在内皮细胞、血管平滑肌细胞、巨噬细胞及其相关细胞因子构成的复杂网络中通过调控血管壁功能、脂质代谢和免疫反应,影响动脉粥样硬化进程。本文着重介绍IncRNAs在动脉粥样硬化血管功能调控中的作用机制。     

小鼠高脂血症模型的竞争性内源RNA调控网络研究

目的基于高通量测序数据,探讨小鼠高脂血症模型中长链非编码RNA(long non-coding RNA,lncRNA)的表达特征及竞争性内源RNA(competitive endogenous RNA,ceRNA)调控网络,筛选lncRNA介导的参与血脂异常发生发展的关键调控通路。方法应用正常饮食和高脂饮食分别诱导ApoE-/-小鼠12周,建立高脂血症模型;进行肝脏全转录组测序,筛选差异表达的lncRNAs、微小RNAs(microRNAs,miRNAs)和信使RNAs(messenger RNAs,mRNAs);对差异表达的mRNAs进行基因功能(Gene Ontology,GO)分析和信号通路(KEGG)注释;结合并分析lncRNA-mRNA共表达关系、miRNA-mRNA靶向关系、lncRNA-miRNA共表达和靶向关系,构建lncRNA介导的ceRNA网络并筛选关键ceRNA调控轴。结果高脂血症小鼠肝脏全转录组测序筛选出117个差异表达lncRNAs、53个差异表达miRNAs和1689个差异表达mRNAs;差异表达的mRNAs主要参与脂质代谢过程、脂肪酸代谢过程和类固醇代谢过程等生物学功能,涉及PPAR信号通路和不饱和脂肪酸合成等途径;构建的ceRNA调控网络包括16个lncRNAs节点、18个miRNAs节点和33个mRNAs节点,其中lnc-Dubr介导的ceRNA调控轴可能对血脂异常具有重要调控作用。结论成功绘制出高脂血症小鼠肝脏lncRNA介导的ceRNA调控网络,并筛选出具有潜在生物学作用的ceRNA调控轴,有望为高脂血症及其他心血管疾病的发生发展和治疗提供新的线索和思路。     

从病毒性心肌炎演变为扩张型心肌病:病毒的作用

病毒感染、宿主免疫反应、以及遗传和环境变化是决定病毒性心肌炎向扩张型心肌病演变的重要因素,其中病毒感染既是启动又是影响疾病发生发展的关键环节。近年研究发现,病毒不仅对心肌细胞有直接和间接损伤作用,而且还通过逃逸宿主先天免疫、诱导免疫因子分泌或表达异常等机制推动疾病进程。抗病毒治疗有益于病毒性心肌炎患者的恢复,在一定程度上抑制扩张型心肌病的发生。     

LncRNAs在消化系统疾病中的研究进展

长链非编码RNA(lncRNAs)是一类长度超过200个核苷酸且无蛋白质编码功能的RNA,能在表观遗传学、转录和转录后水平调控基因表达,广泛参与机体生理和病理过程。近年研究发现lncRNAs在多种消化系统疾病的发生、发展过程中发挥作用,对lncRNAs的研究将为这些疾病发生的预测、诊断和治疗以及预后评估提供有价值的信息。本文在简要介绍lncRNAs基本概念的基础上,对相关研究进展作一综述。     

长链非编码RNA与冠状动脉粥样硬化性心脏病

近年有研究表明,有大量基因序列通过非编码RNA形式对生命活动进行调控。目前对非编码RNA的研究主要集中在微RNA(mi RNA)和长链非编码(long non-coding RNA,lncRNA)。其中,lncRNA是由长度超过200个核苷酸组成的不具有蛋白质编码功能的RNA,它们参与基因组印迹、X染色体沉默以及染色质修饰、转录激活、核内运输、转录干扰等多种重要的调控作用。虽然目前lncRNAs的作用机制和功能尚未完全清楚,但是近年的研究表明,lncRNAs是参与心血管疾病发生、发展的重要调节因子,与冠状动脉粥样硬化性心脏病密切相关。     

巨噬细胞迁移抑制因子的抗寄生虫病作用研究

巨噬细胞迁移抑制因子(MIF)是一种重要的促炎和免疫调节蛋白,作为天然免疫应答级联反应的上游因子,参与调节适应性免疫应答,负反馈调节糖皮质激素的抗炎功能,调节细胞增殖与分化、细胞凋亡和细胞周期,并参与调节多种寄生虫感染与免疫过程。疟原虫、硕大利什曼原虫、马来丝虫等多种寄生虫的MIF与哺乳动物的MIF为同系物,并参与调控虫体与宿主的相互作用,发挥新型的免疫逃避作用。因此,针对抗MIF的小分子抑制物和疫苗的研发为上述相关寄生虫病的预防和治疗提供了一条全新的途经。     

The contribution of long non-coding RNAs in Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBDs) are multifactorial autoimmune diseases with growing prevalence but the interaction between genetic, environmental and immunologic factors in their development is complex and remains obscure. There is great need to understand their pathogenetic mechanisms and evolve diagnostic and therapeutic tools. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that are known to interfere in gene regulation but their roles and functions have not yet been fully understood. While they are widely investigated in cancers, little is known about their contribution in other diseases. There is growing evidence that lncRNAs play critical role in regulation of immune system and that they interfere in the pathogenetic mechanisms of autoimmune diseases, like IBDs. Recent studies have identified lncRNAs in the proximity of IBD-associated genes and single nucleotide polymorphisms within IBD-associated lncRNAs as well. Furthermore, blood samples and pinch biopsies were also analyzed and a plethora of lncRNAs are found to be deregulated in Crohn’s disease (CD), Ulcerative colitis (UC) or both. (Especially in UC samples the lncRNAs INFG-AS1 and BC012900 were found to be significantly up-regulated. Similarly, ANRIL, a lncRNA that nest different disease associated SNPs, is significantly down-regulated in inflamed IBD tissue.) This review aims at recording for the first time recent data about lncRNAs found to be deregulated in IBDs and discussing suggestive pathogenetic mechanisms and future use of lncRNAs as biomarkers.     

Escape and Over-Activation of Innate Immune Responses by SARS-CoV-2: Two Faces of a Coin

In the past 20 years, coronaviruses (CoVs), including SARS-CoV-1, MERS-CoV, and SARS-CoV-2, have rapidly evolved and emerged in the human population. The innate immune system is the first line of defense against invading pathogens. Multiple host cellular receptors can trigger the innate immune system to eliminate invading pathogens. However, these CoVs have acquired strategies to evade innate immune responses by avoiding recognition by host sensors, leading to impaired interferon (IFN) production and antagonizing of the IFN signaling pathways. In contrast, the dysregulated induction of inflammasomes, leading to uncontrolled production of IL-1 family cytokines (IL-1β and IL-18) and pyroptosis, has been associated with COVID-19 pathogenesis. This review summarizes innate immune evasion strategies employed by SARS-CoV-1 and MERS-CoV in brief and SARS-CoV-2 in more detail. In addition, we outline potential mechanisms of inflammasome activation and evasion and their impact on disease prognosis.     

Immune evasion strategies of ranaviruses and innate immune responses to these emerging pathogens

Ranaviruses (RV, Iridoviridae) are large double-stranded DNA viruses that infect fish, amphibians and reptiles. For ecological and commercial reasons, considerable attention has been drawn to the increasing prevalence of ranaviral infections of wild populations and in aquacultural settings. Importantly, RVs appear to be capable of crossing species barriers of numerous poikilotherms, suggesting that these pathogens possess a broad host range and potent immune evasion mechanisms. Indeed, while some of the 95-100 predicted ranavirus genes encode putative evasion proteins (e.g., vIFα, vCARD), roughly two-thirds of them do not share significant sequence identity with known viral or eukaryotic genes. Accordingly, the investigation of ranaviral virulence and immune evasion strategies is promising for elucidating potential antiviral targets. In this regard, recombination-based technologies are being employed to knock out gene candidates in the best-characterized RV member, Frog Virus (FV3). Concurrently, by using animal infection models with extensively characterized immune systems, such as the African clawed frog, Xenopus laevis, it is becoming evident that components of innate immunity are at the forefront of virus-host interactions. For example, cells of the macrophage lineage represent important combatants of RV infections while themselves serving as targets for viral infection, maintenance and possibly dissemination. This review focuses on the recent advances in the understanding of the RV immune evasion strategies with emphasis on the roles of the innate immune system in ranaviral infections.     

Identification of innate immunity genes and pathways using a comparative genomics approach

To reveal regulators of innate immunity, we used RNAi assays to monitor the immune response when genes are inhibited in Caenorhabditis elegans and mouse macrophages. Genes that altered innate immune responsiveness in C. elegans were validated in murine macrophages, resulting in the discovery of 11 genes that regulate the innate immune response in both systems and the subsequent identification of a protein interaction network with a conserved role in innate immunity regulation. We confirmed the role of four of these 11 genes in antimicrobial gene regulation using available mutants in C. elegans. Several of these genes (acy-1, tub-2, and tbc-1) also regulate susceptibility to the pathogen Pseudomonas aeruginosa. These genes may prove critical to understanding host defense and represent potential therapeutic targets for infectious and immunological diseases.     

Viral Evasion of RIG-I-Like Receptor-Mediated Immunity through Dysregulation of Ubiquitination and ISGylation

Viral dysregulation or suppression of innate immune responses is a key determinant of virus-induced pathogenesis. Important sensors for the detection of virus infection are the RIG-I-like receptors (RLRs), which, in turn, are antagonized by many RNA viruses and DNA viruses. Among the different escape strategies are viral mechanisms to dysregulate the post-translational modifications (PTMs) that play pivotal roles in RLR regulation. In this review, we present the current knowledge of immune evasion by viral pathogens that manipulate ubiquitin- or ISG15-dependent mechanisms of RLR activation. Key viral strategies to evade RLR signaling include direct targeting of ubiquitin E3 ligases, active deubiquitination using viral deubiquitinating enzymes (DUBs), and the upregulation of cellular DUBs that regulate RLR signaling. Additionally, we summarize emerging new evidence that shows that enzymes of certain coronaviruses such as SARS-CoV-2, the causative agent of the current COVID-19 pandemic, actively deISGylate key molecules in the RLR pathway to escape type I interferon (IFN)-mediated antiviral responses. Finally, we discuss the possibility of targeting virally-encoded proteins that manipulate ubiquitin- or ISG15-mediated innate immune responses for the development of new antivirals and vaccines.     

Hepatitis C Virus and Innate Immunity: Taking a Fresh Look into an Old Issue

The innate immune response represents the first line of defense against hepatitis C virus (HCV) infection. The response is an early, coordinated effort orchestrated by host interferon (IFN) production, natural killer cell activation, and dendritic cell maturation, which, when effective, primes a successful adaptive immune response, leading to resolution of infection. Numerous mechanisms allow subversion of innate immunity, often establishing chronicity and resistance to conventional antiviral therapy. Recent groundbreaking studies examining viral evasion of host defenses and genetic host determinants of response to IFN have advanced our understanding of the innate immune response to HCV. This has provided the framework for individualized treatment approaches and the development of novel therapeutics aimed at restoring innate immune signaling during chronic infection. The objective of this report is to review advances in our understanding of HCV and host innate immune defenses, and to highlight their clinical translation.     

Status of hepatitis C virus vaccination:Recent update

Hepatitis C virus(HCV) infection is still a major public health problem worldwide since its first identification in 1989. At the start, HCV infection was post-transfusion viral infection, particularly in developing countries. Recently, due to iv drug abuse, HCV infection became number one health problem in well-developed countries as well. Following acute HCV infection, the innateimmune response is triggered in the form of activated coordinated interaction of NK cells, dendritic cells and interferon α. The acquired immune response is then developed in the form of the antibody-mediated immune response(ABIR) and the cell-mediated immune response(CMIR). Both are responsible for clearance of HCV infection in about 15% of infected patients. However, HCV has several mechanisms to evade these antivirus immune reactions. The current review gives an overview of HCV structure, immune response and viral evasion mechanisms. It also evaluates the available preventive and therapeutic vaccines that induce innate, ABIR, CMIR. Moreover, this review highlights the progress in recent HCV vaccination studies either in preclinical or clinical phases. The unsatisfactory identification of HCV infection by the current screening system and the limitations of currently available treatments, including the ineligibility of some chronic HCV patients to such antiviral agents, mandate the development of an effective HCV vaccine.     

Diagnostic and prognostic potential of tissue and circulating long non-coding RNAs in colorectal tumors

Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.     

肝细粒棘球蚴病的免疫研究进展

棘球蚴感染过程中，宿主的免疫应答机制十分复杂，免疫保护和免疫损伤并存。研究肝细粒棘球蚴免疫机制，将有助于阐明肝棘球蚴病的病理机制及调整恢复机体的正常免疫功能，为预防和治疗肝棘球蚴病提供一定的依据。