真菌细胞外囊泡的研究进展CSCD

细胞外囊泡(extracellular vesicles,EVs)是一种细胞分泌的膜性囊泡。研究表明EVs在细胞生命的许多方面起着重要作用,包括细胞间的通讯、发病机制和癌症进展[1]。然而,EVs在微生物学中的作用却研究较少,EVs在微生物中最先是在革兰氏阴性菌中发现的[2],后续的研究表明它们在革兰氏阳性菌中也普遍存在[3],此后也有研究发现其在病毒致病过程中的作用和机制。目前,关于EVs与真菌感染关系的研究甚少,本综述将介绍EVs在真菌中的相关研究进展。     

鱼类肠道微生物与宿主免疫系统相互作用研究进展

鱼类肠道中存在大量微生物,对于维持宿主健康具有重要作用。鱼类免疫系统能够监视并调控肠道微生物组成,维持肠道菌群稳态。同时,鱼类肠道共生微生物调节鱼类免疫系统,抑制病原微生物的过度增殖,保证宿主的健康。本文回顾了鱼类肠道微生物与宿主免疫系统相互作用的研究进展,重点介绍了宿主免疫系统识别肠道微生物、塑造肠道菌群以及益生菌对宿主免疫和肠道菌群的调控等,提出了理想的益生菌应该来自动物自身胃肠道,生产中应谨慎选用非宿主来源的益生菌,以期为推动鱼类肠道功能微生物开发和应用提供理论支撑。     

肠道菌群与胆汁酸代谢的互相作用

肠道菌群是胃肠道的多种共生细菌和其他微生物的统称,是一个复杂而动态的微生物生态系统,有数十万亿个微生物。胆汁酸是胆汁的主要成分,由肝脏中的胆固醇合成并释放到肠道中以帮助消化吸收膳食脂肪。肠道菌群在胆汁酸代谢中发挥着重要作用,它借助胆盐水解酶和类固醇脱氢酶等通过脱氢、脱羟基和脱硫等作用改变胆汁酸池的组成;随后通过影响胆汁酸受体(如法尼醇X受体)再反馈调节胆汁酸代谢。此外胆汁酸可通过破坏细菌细胞膜和损伤DNA等抑制细菌的生长而直接改变肠道菌群结构,也可通过其受体间接改变肠道菌群结构。越来越多的研究揭示了肝脏胆汁酸和肠道菌群在调节宿主健康和疾病中的相互作用。因此,了解肠道菌群和胆汁酸代谢之间的相互作用对维持宿主健康具有重要意义。本文就胆汁酸的基本代谢过程以及其与肠道菌群的相互作用作一综述。     

干细胞来源的胞外囊泡对T细胞的免疫调控作用

胞外囊泡（EVs）是细胞旁分泌产生的一种亚细胞成分,实质上是一组纳米级颗粒。它是双层膜结合型囊泡,内含蛋白质、核酸等活性成分。EVs在细胞间通过转移携带的信号分子而获得重要的地位。目前关于EVs在体外和体内的研究中对T细胞的调控能力引起了人们广泛的兴趣。在大多数研究中干细胞被报道能够抑制T细胞的增殖、活化和分化,在极少数研究中也发现干细胞具有增强T细胞免疫反应的作用。事实上所有的细胞类型均能释放EVs,包括干/祖/前体细胞。EVs被认为是细胞间交流的一种新机制,具有与干/祖细胞等亲代细胞相似的免疫调控作用。本综述是概述干/祖细胞来源的EVs对T细胞调控作用及可能的机制。     

细胞外囊泡在肾脏病治疗中的研究进展

细胞外囊泡(extracellular vesicles, EVs)是细胞分泌的由脂质双分子层包绕形成的膜性囊泡,其内包含丰富的生物学信息,参与多种生理和病理过程。近年来,EVs在疾病治疗中也展现出了巨大应用前景,一方面来源于干细胞的EVs可以直接发挥治疗作用,另一方面EVs还可以作为一种天然的药物递送载体,为疾病的治疗提供新的给药策略。本文聚焦EVs在肾脏病治疗中的应用和研究进展。     

肠道中多不饱和脂肪酸及其衍生物研究进展

肠道菌群是人体微生态学的重要组成部分,也是最大、最复杂的微生态系统,在宿主的营养吸收、肠道与免疫系统发育等重要生理过程中发挥作用,与人类健康和疾病密切相关。这些共生微生物排除肠道病原体的功能主要依赖于其产生的生物活性物质,如多不饱和脂肪酸等。同时这些脂肪酸在肠道微生物的作用下能够进一步转化为具有特殊结构和功能的多不饱和脂肪酸衍生物。这些多不饱和脂肪酸衍生物对维持健康稳定的肠道菌群至关重要。此外,多不饱和脂肪酸在宿主防御和免疫中发挥了多重关键作用,包括抗癌、抗炎、抗氧化活性,以及降低肠道致病菌的竞争能力等。主要对肠道中多不饱和脂肪酸的来源及其重要的生理功能,以及肠道微生物对多不饱和脂肪酸的转化衍生机制进行了综述,并提出肠道微生物是特殊多不饱和脂肪酸及衍生物生产菌株潜在的种子及基因库,以扩展功能油脂生产菌株的来源。     

肠道菌群与代谢研究进展

从出生伊始肠道菌群就依赖于宿主的基因组、营养和生活方式而变化的,与宿主共同进化发展.肠道菌群参与调控其宿主的多种代谢途径,包括宿主的免疫、营养,并且极大地影响宿主的物质能量代谢及与物质能量代谢相关疾病的发生与发展过程.同时又与多个器官共同作用,在宿主的代谢、信息传递,疾病的感染与防御方面起非常重要的作用.深入了解肠道菌群在其参与代谢的具体作用,对理解物质能量代谢相关疾病病因、优化治疗策略、调节肠道菌群、防治疾病和提高宿主健康水平具有重要作用.本研究对人类肠道菌群的形成、物质能量代谢、代谢相关疾病及其防治等方面的研究进展加以综述.     

动物宿主——肠道微生物代谢轴研究进展

肠道中栖息着数量庞大且复杂多样的微生物菌群,在维持宿主肠道微环境稳态中发挥重要作用。微生物菌群可以利用宿主肠道的营养素,发酵产生代谢产物,与宿主机体形成宿主—微生物代谢轴(host-microbe metabolic axis)。该代谢轴既能影响营养素吸收和能量代谢,又可调控宿主各项生理过程。本文主要阐述宿主-肠道微生物代谢轴的概念、肠-肝轴、肠-脑轴、肠道微生物与宿主肠道代谢轴的互作以及对机体健康的影响。     

细胞外囊泡在非酒精脂肪肝发病机制及诊断治疗中的作用

非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)是21世纪全球最重要的公共健康问题之一,也是我国愈来愈重要的慢性肝病问题。细胞间通讯在NAFLD病理进程中发挥重要作用。细胞外囊泡(extracellular vesicles, EVs)是近年来备受关注的细胞间通讯方式。EVs携带脂质、蛋白质、DNA、mRNA以及非编码RNA等作为信号分子在细胞间的物质和信息交流中起重要作用,参与了多个生理病理过程。目前细胞外囊泡在非酒精脂肪肝发病机制及诊断治疗中的作用方面的研究非常有限,但初步研究显示, EVs在NAFLD病程发展中发挥重要作用。因此,该文重点关注EVs参与NAFLD病程机制研究,并对其在NAFLD防治中的潜在诊疗价值作简要综述。     

蜜蜂肠道菌群定殖研究进展

肠道菌群在其宿主健康中发挥着各种各样的重要功能。蜜蜂是高度社会化的昆虫,其肠道菌群与大多数昆虫明显不同,由兼性厌氧和微好氧的细菌组成,具有高度保守性和专门的核心肠道微生物群。近年来的研究表明,蜜蜂肠道微生物群在代谢、免疫功能、生长发育以及保护机体免受病原体侵袭等方面起着重要作用,并已证实肠道微生物在蜜蜂健康和疾病中起着重要作用,肠道微生物群的破坏对蜜蜂健康会产生不利影响。本文综述了蜜蜂肠道菌群的特征及菌群定殖研究进展,介绍了蜜蜂的日龄、群体、季节等对蜜蜂肠道菌群定殖的影响,探讨了宿主的功能和新陈代谢对肠道菌群的影响。     

Microvesicles and exosomes in metabolic diseases and inflammation

Metabolic diseases are based on a dysregulated crosstalk between various cells such as adipocytes, hepatocytes and immune cells. Generally, hormones and metabolites mediate this crosstalk that becomes alterated in metabolic syndrome including obesity and diabetes. Recently, Extracellular Vesicles (EVs) are emerging as a novel way of cell-to-cell communication and represent an attractive strategy to transfer fundamental informations between the cells through the transport of proteins and nucleic acids. EVs, released in the extracellular space, circulate via the various body fluids and modulate the cellular responses following their interaction with the near and far target cells. Clinical and experimental data support their role as biomarkers and bioeffectors in several diseases includimg also the metabolic syndrome. Despite numerous studies on the role of macrophages in the development of metabolic diseases, to date, there are little informations about the influence of metabolic stress on the EVs produced by macrophages and about the role of the released vesicles in the organism. Here, we review current understanding about the role of EVs in metabolic diseases, mainly in inflammation status burst. This knowledge may play a relevant role in health monitoring, medical diagnosis and personalized medicine.     

Extracellular vesicles from thyroid cancer harbor a functional machinery involved in extracellular matrix remodeling

Extracellular vesicles (EVs) participate in cell-stroma crosstalk within the tumor microenvironment and fibroblasts (Fb) contribute to tumor promotion in thyroid cancer. However, the role of tumor-stroma derived EVs still needs to be deciphered. We hypothesized that the interaction of thyroid tumor cells with Fb would liberate EVs with a specific proteomic profile, which would have an impact on EV-functionality in thyroid tumor progression-related events. Tumor (TPC-1, 8505c) and non-tumor (NThyOri) thyroid cells were co-cultured with human Fb. EVs, obtained by ultracentrifugation of conditioned media, were characterized by nanoparticle tracking analysis and western blotting. EV-proteomic analysis was performed by mass-spectrometry, and metalloproteinases (MMPs) were studied by zymography. EV-exchange was evaluated using immunofluorescence, confocal microscopy and FACS. EVs expressed classical exosome markers, with EVs from thyroid tumor cell-Fb co-cultures showing a proteomic profile related to extracellular matrix (ECM) remodeling. Bidirectional crosstalk between Fb and TPC-1 cells produced significantly more EVs than their isolated cells, and potentiated EV-functionality. In line with this, Fb-TPC-1 derived EVs induced MMP2 activation in NThyOri supernatants, and MMP2 activity could be evidenced in Fb and TPC-1 contact-independent co-cultures. Besides, MMP2 interactors allowed us to discriminate between EVs from thyroid tumoral and non-tumoral milieus. Interestingly, Fb internalized more EVs from TPC-1 than from NThyOri producing cells. Fb and thyroid tumor cell crosstalk produces specialized EVs with an ECM remodeling proteomic profile, enabling activation of MMP2 and possibly facilitating ECM-degradation, which is potentially linked with thyroid tumor progression.     

Cardioprotective role of extracellular vesicles: A highlight on exosome beneficial effects in cardiovascular diseases

Extracellular vesicles (EVs) are nano-sized vesicles, released from many cell types including cardiac cells, have recently emerged as intercellular communication tools in cell dynamics. EVs are an important mediator of signaling within cells that influencing the functional behavior of the target cells. In heart complex, cardiac cells can easily use EVs to transport bioactive molecules such as proteins, lipids, and RNAs to the regulation of neighboring cell function. Cross-talk between intracardiac cells plays pivotal roles in the heart homeostasis and in adaptive responses of the heart to stress. EVs were released by cardiomyocytes under baseline conditions, but stress condition such as hypoxia intensifies secretome capacity. EVs secreted by cardiac progenitor cells and cardiosphere-derived cells could be pinpointed as important mediators of cardioprotection and cardiogenesis. Furthermore, EVs from many different types of stem cells could potentially exert a therapeutic effect on the damaged heart. Recent evidence shows that cardiac-derived EVs are rich in microRNAs, suggesting a key role in the controlling of cellular processes. EVs harboring exosomes may be clinically useful in cell-free therapy approaches and potentially act as prognosis and diagnosis biomarkers of cardiovascular diseases.     

Exosomes,autophagy and ER stress pathways in human diseases: Cross-regulation and therapeutic approaches

Exosomal release pathway and autophagy together maintain homeostasis and survival of cells under stressful conditions. Autophagy is a catabolic process through which cell entities, such as malformed biomacromolecules and damaged organelles, are degraded and recycled via the lysosomal-dependent pathway. Exosomes, a sub-type of extracellular vesicles (EVs) formed by the inward budding of multivesicular bodies (MVBs), are mostly involved in mediating communication between cells. The unfolded protein response (UPR) is an adaptive response that is activated to sustain survival in the cells faced with the endoplasmic reticulum (ER) stress through a complex network that involves protein synthesis, exosomes secretion and autophagy. Disruption of the critical crosstalk between EVs, UPR and autophagy may be implicated in various human diseases, including cancers and neurodegenerative diseases, yet the molecular mechanism(s) behind the coordination of these communication pathways remains obscure. Here, we review the available information on the mechanisms that control autophagy, ER stress and EV pathways, with the view that a better understanding of their crosstalk and balance may improve our knowledge on the pathogenesis and treatment of human diseases, where these pathways are dysregulated.     

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles: A novel therapeutic paradigm

Mesenchymal stem cells (MSCs) have been revealed to hold great potential for the development of new treatment approaches for various diseases. However, the clinical use of these cells is limited due to their tumorigenic effects. The therapeutic benefits of MSCs are largely dependent on paracrine factors including extracellular vesicles (EVs). EVs are nano-sized bilayer membrane structures containing lipids, microRNAs and proteins which play key roles in cell-to-cell communications. Because of their lower immunogenicity, tumorigenicity, and easier management, EVs have emerged as a new promising alternative to whole-cell therapy. Therefore, this paper reviews current preclinical studies on the use of EVs derived from human umbilical cord MSCs (hucMSCs) as a therapeutic approach in treatment of several diseases including neurological, cardiovascular, liver, kidney, and bone diseases as well as the cutaneous wound, inflammatory bowel disease, cancers, infertility, and other disorders.     

The role of extracellular vesicles in podocyte autophagy in kidney disease

Podocytes are the key cells involved in protein filtration in the glomerulus. Once proteins appear in the urine when podocytes fail, patients will end with renal failure due to the progression of glomerular damage if no proper treatment is applied. The injury and loss of podocytes can be attributed to diverse factors, such as genetic, immunologic, toxic, or metabolic disorders. Recently, autophagy has emerged as a key mechanism to eliminate the unwanted cytoplasmic materials and to prolong the lifespan of podocytes by alleviating cell damage and stress. Typically, the fundamental function of extracellular vesicles (EVs) is to mediate the intercellular communication. Recent studies have suggested that, EVs, especially exosomes, play a certain role in information transfer by communicating proteins, mRNAs, and microRNAs with recipient cells. Under physiological and pathological conditions, EVs assist in the bioinformation interchange between kidneys and other organs. It is suggested that EVs are related to the pathogenesis of acute kidney injury and chronic kidney disease, including glomerular disease, diabetic nephropathy, renal fibrosis and end-stage renal disease. However, the role of EVs in podocyte autophagy remains unclear so far. Here, this study integrated the existing information about the relevancy, diagnostic value and therapeutic potential of EVs in a variety of podocytes-related diseases. The accumulating evidence highlighted that autophagy played a critical role in the homeostasis of podocytes in glomerular disease.     

Integrated gut/liver microphysiological systems elucidates inflammatory inter‐tissue crosstalk

A capability for analyzing complex cellular communication among tissues is important in drug discovery and development, and in vitro technologies for doing so are required for human applications. A prominent instance is communication between the gut and the liver, whereby perturbations of one tissue can influence behavior of the other. Here, we present a study on human gut‐liver tissue interactions under normal and inflammatory contexts, via an integrative multi‐organ platform comprising human liver (hepatocytes and Kupffer cells), and intestinal (enterocytes, goblet cells, and dendritic cells) models. Our results demonstrated long‐term (>2 weeks) maintenance of intestinal (e.g., barrier integrity) and hepatic (e.g., albumin) functions in baseline interaction. Gene expression data comparing liver in interaction with gut, versus isolation, revealed modulation of bile acid metabolism. Intestinal FGF19 secretion and associated inhibition of hepatic CYP7A1 expression provided evidence of physiologically relevant gut‐liver crosstalk. Moreover, significant non‐linear modulation of cytokine responses was observed under inflammatory gut‐liver interaction; for example, production of CXCR3 ligands (CXCL9,10,11) was synergistically enhanced. RNA‐seq analysis revealed significant upregulation of IFNα/β/γ signaling during inflammatory gut‐liver crosstalk, with these pathways implicated in the synergistic CXCR3 chemokine production. Exacerbated inflammatory response in gut‐liver interaction also negatively affected tissue‐specific functions (e.g., liver metabolism). These findings illustrate how an integrated multi‐tissue platform can generate insights useful for understanding complex pathophysiological processes such as inflammatory organ crosstalk. Biotechnol. Bioeng. 2017;114: 2648–2659. © 2017 Wiley Periodicals, Inc.     

The roles of parasite-derived extracellular vesicles in disease and host-parasite communication

In recent years, several parasites have been shown to interact with their hosts through intra- and inter-community communication mechanisms, which were identified to be mediated by extracellular vesicles (EVs) through various uptake mechanisms. EVs are a heterogenous group of nanoparticles (~30–5000 nm) classified into three main types according to their size and biogenesis. EVs contain proteins, lipids, nucleic acids and metabolites from the cell of origin which are essential for genetic exchange, biomarker identification and diagnosis of pathological diseases. As important “forward lines of parasite infectivity”, the parasite-secreted EVs function as information transmitters in the early-stage of host-parasite interaction and subsequent host-cell colonization. For this review, we summarize from the literature the relevance of EVs to the pathogenesis and development of human parasitic protistan diseases such as giardiasis, leishmaniasis, amoebiasis, malaria and Blastocystis-mediated gut pathology. Specific in vitro and in vivo interactions of the parasite-EVs and the host, with the reported cellular and immunological outcomes are discussed in this review. EVs have great potential to be further developed as diagnostic, immunomodulation and therapeutic alternatives to fill the knowledge gaps in the current parasitic diseases discussed in this review. Nanomedicine and vaccine development could be explored, with the utilization and/or modification of the parasitic EVs as novel treatment and prevention strategies.     

Extracellular vesicles in normal pregnancy and pregnancy‐related diseases

Extracellular vesicles (EVs) are nanosized, membranous vesicles released by almost all types of cells. Extracellular vesicles can be classified into distinct subtypes according to their sizes, origins and functions. Extracellular vesicles play important roles in intercellular communication through the transfer of a wide spectrum of bioactive molecules, contributing to the regulation of diverse physiological and pathological processes. Recently, it has been established that EVs mediate foetal‐maternal communication across gestation. Abnormal changes in EVs have been reported to be critically involved in pregnancy‐related diseases. Moreover, EVs have shown great potential to serve as biomarkers for the diagnosis of pregnancy‐related diseases. In this review, we discussed about the roles of EVs in normal pregnancy and how changes in EVs led to complicated pregnancy with an emphasis on their values in predicting and monitoring of pregnancy‐related diseases.     

The key role of extracellular vesicles in the metastatic process

Extracellular vesicles (EVs), including exosomes, have a key role in the paracrine communication between organs and compartments. EVs shuttle virtually all types of biomolecules such as proteins, lipids, nucleic acids, metabolites and even pharmacological compounds. Their ability to transfer their biomolecular cargo into target cells enables EVs to play a key role in intercellular communication that can regulate cellular functions such as proliferation, apoptosis and migration. This has led to the emergence of EVs as a key player in tumor growth and metastasis through the formation of “tumor niches” in target organs. Recent data have also been shown that EVs may transform the microenvironment of primary tumors thus favoring the selection of cancer cells with a metastatic behavior. The release of EVs from resident non-malignant cells may contribute to the metastatic processes as well. However, cancer EVs may induce malignant transformation in resident mesenchymal stem cells, suggesting that the metastatic process is not exclusively due to circulating tumor cells. In this review, we outline and discuss evidence-based roles of EVs in actively regulating multiple steps of the metastatic process and how we can leverage EVs to impair metastasis.