外泌体在肥胖症中的研究进展

外泌体是细胞分泌的一种囊泡样小体,可通过受体与配体间的相互作用刺激靶细胞,或通过向靶细胞转移各种生物活性分子如膜受体、蛋白质、mRNA和miRNA等方式在细胞间通讯中扮演重要角色,其中研究最多的是miRNAs。最近研究表明,外泌体中特定的miRNAs通过调控脂肪的形成、经典棕色脂肪组织功能和白色脂肪组织褐变过程,以及参与脂肪组织巨噬细胞的活化状态,在肥胖症的病理过程中发挥关键作用。     

骨相关细胞来源外泌体miRNA调节骨形成的研究进展

外泌体是一种由细胞分泌的具有脂质双分子层结构的杯状细胞外囊泡,直径约30-150 nm。近年来,研究表明骨组织中的各类骨细胞产生的外泌体不仅可介导生理情况下骨髓微环境内的细胞间通讯,维持骨髓微环境的稳态,还参与骨骼疾病的发病过程。该文将着重探讨骨相关细胞来源的外泌体miRNA对骨形成的调节作用。     

不同细胞来源的外泌体在动脉粥样硬化中的研究进展

外泌体是细胞分泌的纳米级膜微粒,能在细胞与细胞之间传递信息。外泌体参与调控细胞的生理活动,在动脉粥样硬化(atherosclerosis,AS)的发生发展中发挥重要作用。作为细胞外囊泡,外泌体受到越来越多的关注,该文综述AS相关细胞(免疫细胞、血小板、血管内皮细胞、血管平滑肌细胞)来源的外泌体在AS发病过程中的作用。     

外泌体在脑卒中病理过程中的作用及机制研究

外泌体是直径30~120 nm的细胞外脂双层囊泡。作为运输信号分子的载体,外泌体能够促使神经血管单元内细胞间通讯,这一功能主要与脑卒中发病后神经元、星形胶质细胞和内皮细胞损伤病理情况有关。外泌体介导神经元病理机制包括：调节神经元发生,促进神经元重塑,适应应激条件以及抑制免疫反应;调节星形胶质细胞的生长,维护血管内皮完整性等。根据外泌体的特性及其作用机制,近年来将外泌体作为生物标志物以及作为药物载体用以诊断或治疗脑卒中的研究不断增加。本文对外泌体在脑卒中发生、发展病理过程中的作用机制和应用进行综述。     

外泌体在脑靶向递送中的应用

血脑屏障(blood brain barrier, BBB)限制了大部分药物的脑靶向递送,进而影响神经系统疾病有效治疗。外泌体作为细胞衍生的纳米囊泡,可参与物质的细胞间运输、介导细胞间通讯和调节机体生物功能等,具有低免疫原性、低毒性及可天然跨越BBB的优点,在脑靶向递送中发挥重要作用。本文概括了外泌体分类、来源、脑靶向递送机制及其在脑部疾病中发挥的作用,为其临床应用提供参考。     

治疗性外泌体的研究进展

外泌体是一种活细胞分泌的囊性小泡,携带大量具有组织或细胞特异性的蛋白质、脂质及遗传物质,可调控不同的生理活动,因此作为一类新兴的治疗药物被广泛研究。间充质干细胞(mesenchymal stem cells, MSCs)和树突状细胞(dendritic cells, DCs)衍生的外泌体是研究较为广泛的两类外泌体,已有许多临床前及临床研究表明其在肺部疾病、肝脏疾病、神经系统疾病及肿瘤等疾病中展现出良好的治疗效果。另外,巨噬细胞、肿瘤细胞和植物细胞等众多其他细胞衍生的外泌体也因其治疗潜力受到越来越多的关注。除了天然来源的外泌体,工程化外泌体的研究也取得许多进展。已报道的外泌体工程化手段种类繁多,如外泌体靶向修饰、外泌体包载活性成分等。本文总结了不同来源的治疗性外泌体的研究进展,并讨论了外泌体的应用前景与未来可能遇到的挑战。     

外泌体对组织纤维化调节作用的研究进展

外泌体是由细胞释放的一种纳米囊泡,包括心肌细胞、肝细胞及多种干细胞在内的各种细胞都会释放外泌体。外泌体在细胞间起着通讯作用,它携带着信使RNA、微RNA和蛋白质参与了几乎所有病理生理过程。组织细胞损伤后释放的外泌体能通过触发炎症、激活成纤维细胞等途径启动修复和(或)再生反应,导致组织纤维化。而干细胞释放的外泌体则能通过促进细胞存活、减少细胞凋亡等途径减轻组织纤维化。本文综述不同来源的外泌体对几种常见组织纤维化调节作用的研究进展。     

外泌体与糖尿病肾病相关研究的最新进展

糖尿病肾病是肾功能衰竭的主要原因,也是发达国家终末期肾病(ESRD)发生的原因之一。外泌体是由细胞产生并存在于体液中的细胞外囊泡(EV),含有在细胞间通讯中发挥着关键作用的多种生物分子,参与多种肾脏疾病的发生发展。对外泌体的研究为糖尿病肾病的诊疗提供了新的途径和思路。故将对外泌体在糖尿病肾病中的研究做简单的综述。     

外泌体在心肌疾病中的研究进展

外泌体是具有脂双层膜的细胞外囊泡,其通过携带丰富的微小RNA(miRNA)等生物分子传递信息,是细胞间通讯的关键介质。外泌体通过参与炎症反应、内皮细胞损伤、心肌纤维化等过程来影响各种心肌疾病的发生发展,在心肌的损伤和修复中起着非常重要的作用。本文主要就近几年发现的外泌体在各种心肌疾病中的机制、诊断及治疗等方面的作用展开综述。     

外泌体miRNA介导的细胞间通讯在骨与软骨组织疾病中的作用研究进展

目的 外泌体是细胞间信息传递的重要载体,对骨科疾病发病机理的研究具有重要意义。本文对骨与软骨组织中功能细胞的外泌体miRNA介导的细胞间通讯作用及机制进行总结与归纳,期望为骨科疾病治疗提供参考。方法 以"外泌体" "成骨细胞" "破骨细胞" "软骨细胞" "miRNA" "骨质疏松" "骨关节炎"为检索词,检索中国知网、维普文献数据库和PubMed数据库,归纳、分析相关文献,对破骨细胞、成骨细胞或软骨细胞外泌体中的miRNA介导细胞间通讯的机制进行总结综述。结果 外泌体miRNA可用于阐释骨与软骨组织疾病机理,作为疾病生物标志物,及参与靶向给药等。结论 外泌体miRNA介导的细胞间通讯为骨与软骨组织疾病的治疗提供新的思路。     

Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases

In the inflammatory microenvironment, there are numerous exosomes secreted by immune cells (Macrophages, neutrophils, dendritic cells), mesenchymal stem cells (MSCs) and platelets as intercellular communicators, which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors. Due to their good biocompatibility, accurate targeting, low toxicity and immunogenicity, these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors. Therefore, the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention. Here we review current knowledge and techniques for exosome identification, isolation, modification and drug loading. More importantly, we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis (RA), osteoarthritis (OA), atherosclerosis (AS), and inflammatory bowel disease (IBD). Finally, we also discuss their potential and challenges as anti-inflammatory drug carriers.     

核受体作为炎症性肠疾病治疗靶点的研究进展

炎症性肠疾病是一种慢性肠道炎症疾病,其发病机制尚不明确,目前多认为与炎症和肠黏膜损伤有关。核受体是一种重要的转录调节因子,包括孕烷X受体(pregnane X receptor,PXR)、法尼酯X受体(farnesoid X receptor,FXR)和组成型雄甾烷受体(constitutive androstane receptor,CAR)等。近年深入研究发现,核受体可以通过抑制炎症信号通路、调节肠道紧密连接蛋白及代谢酶的表达减轻肠道炎症,并维持肠黏膜屏障功能,在炎症性肠疾病肠道保护方面发挥重要作用。因此,本文综述核受体PXR、FXR和CAR对炎症性肠疾病肠道的保护作用机制,为以核受体为靶点的炎症性肠疾病药物治疗提供新思路。     

A new target for the treatment of inflammatory bowel disease: Interleukin-37

Interleukin (IL)-37 belongs to the IL-1 cytokine family. It has anti-inflammatory effects on numerous autoimmune diseases such as asthma, psoriasis, inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA). Mechanistically, IL-37 plays an anti-inflammatory role by regulating the expression of inflammatory factors in two ways: binding extracellular receptors IL-18R or transferring into the nucleus with Smad3. IBD is a kind of idiopathic intestinal inflammatory disease with unknown etiology and pathogenesis. Recent researches had proved that IL-37 is negatively involved in the pathogenesis and development of IBD. Among various inflammatory diseases, IL-37 has been shown to regulate inflammatory development by acting on various immune cells such as neutrophils, macrophages (Mϕ), dendritic cells (DCs), T cells and intestinal epithelial cells. This review summarizes the biological role of IL-37, and its immunoregulatory effects on the immune cells, especially anti-inflammatory function in both human and experimental models of IBD.     

Exosomes and exosomal miRNAs in cardiovascular protection and repair

Cell–cell communication between cardiac and vascular cells and from stem and progenitor cells to differentiated cardiovascular cells is both an important and complex process, achieved through a diversity of mechanisms that have an impact on cardiovascular biology, disease and therapeutics. In recent years, evidence has accumulated suggesting that extracellular vesicles (EVs) are a new system of intercellular communication. EVs of different sizes are produced via different biogenesis pathways and have been shown to be released and taken up by most of known cell types, including heart and vascular cells, and stem and progenitor cells. This review will focus on exosomes, the smallest EVs (up to 100 nm in diameter) identified so far. Cells can package cargoes consisting of selective lipids, proteins and RNA in exosomes and such cargoes can be shipped to recipient cells, inducing expressional and functional changes. This review focuses on exosomes and microRNAs in the context of cardiovascular disease and repair. We will describe exosome biogenesis and cargo formation and discuss the available information on in vitro and in vivo exosomes-based cell-to-cell communication relevant to cardiovascular science. The methods used in exosome research will be also described. Finally, we will address the promise of exosomes as clinical biomarkers and their impact as a biomedical tool in stem cell-based cardiovascular therapeutics.     

调节性T细胞与炎性肠病研究进展

炎性肠病(Inflammatory bowel disease,IBD)为非特异性炎症性肠病,主要包括溃疡性结肠炎(Ul-cerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。其病因和发病机制尚未完全明确。已知肠道粘膜免疫系统异常反应所导致的炎症反应在IBD中发挥着重要作用。笔者对调节性T细胞在肠道免疫系统中的作用与IBD的发病机制相关性的研究进展做一综述,为临床治疗IBD的新药研究提供可能性的途径。     

Is It Time to Use Modeling of Cellular Transporter Homeostasis to Inform Drug-Drug Interaction Studies: Theoretical Considerations

Cardiovascular disease (CAD) due to atherosclerosis is a major cause of death worldwide. The development of atherosclerosis involves intercellular communication facilitated by exosomes secreted from vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), immune cells, and platelets. In this review, we summarize the current understanding of exosome biogenesis and uptake, and discuss atherogenic and atheroprotective functions of exosomes secreted from these cell types. In addition, we examine the potential of enhancing the therapeutic and targeting ability of exosomes exhibiting atheroprotective function by drug loading and surface modification with targeting ligands. We conclude with current challenges associated with exosome engineering for therapeutic use.

     

肠道微生态与炎症性肠病

炎症性肠病(inflammatory bowel disease,IBD)是一组病因未明、发病机制亦不明确的慢性肠道炎症性疾病,主要包括克罗恩病(Crohn's disease,CD)和溃疡性结肠炎(ulcerative colitis,UC)。近几十年的研究结果认为,其发病是环境、易感基因和肠道微生态3个要素相互作用的结果,且这些要素使IBD成为一种适合研究宿主与肠道微生物相互作用的高优先平台。最近,肠道菌群的图谱分析将IBD的发病机制与菌群各组成部分特征的改变相联系,进一步支持"肠道微生物和宿主相互作用的改变能形成IBD"这一观点。该文回顾性分析有关IBD患者体内微生物的研究文献,综述肠道微生态失衡对IBD的多方面影响,以动物模型和临床验证资料阐述不同的治疗方法改善肠道微生态变化的最新进展。