Cellular prion protein in human plasma–derived extracellular vesicles promotes neurite outgrowth via the NMDA receptor–LRP1 receptor system

Exosomes and other extracellular vesicles (EVs) participate in cell–cell communication. Herein, we isolated EVs from human plasma and demonstrated that these EVs activate cell signaling and promote neurite outgrowth in PC-12 cells. Analysis of human plasma EVs purified by sequential ultracentrifugation using tandem mass spectrometry indicated the presence of multiple plasma proteins, including α₂-macroglobulin, which is reported to regulate PC-12 cell physiology. We therefore further purified EVs by molecular exclusion or phosphatidylserine affinity chromatography, which reduced plasma protein contamination. EVs subjected to these additional purification methods exhibited unchanged activity in PC-12 cells, even though α₂-macroglobulin was reduced to undetectable levels. Nonpathogenic cellular prion protein (PrP^C) was carried by human plasma EVs and essential for the effects of EVs on PC-12 cells, as EV-induced cell signaling and neurite outgrowth were blocked by the PrP^C-specific antibody, POM2. In addition, inhibitors of the N-methyl-d-aspartate (NMDA) receptor (NMDA-R) and low-density lipoprotein receptor–related protein-1 (LRP1) blocked the effects of plasma EVs on PC-12 cells, as did silencing of Lrp1 or the gene encoding the GluN1 NMDA-R subunit (Grin1). These results implicate the NMDA-R–LRP1 complex as the receptor system responsible for mediating the effects of EV-associated PrP^C. Finally, EVs harvested from rat astrocytes carried PrP^C and replicated the effects of human plasma EVs on PC-12 cell signaling. We conclude that interaction of EV-associated PrP^C with the NMDA-R–LRP1 complex in target cells represents a novel mechanism by which EVs may participate in intercellular communication in the nervous system.     

Bacterial outer membrane vesicles,a potential vaccine candidate in interactions with host cells based

Both Gram-Positive and Gram-Negative bacteria can secrete outer membrane vesicles (OMVs) in their growth and metabolism process. Originally, OMVs were considered as a by-product of bacterial merisis. However, many scientists have reported the important role of OMVs in many fields recently. In this review, we briefly introduce OMVs biological functions and then summarize the findings about the OMVs interactions with host cells. At last, we will make an expectation about the prospects of the application of OMVs as vaccines.     

Identification of distinct N-glycosylation patterns on extracellular vesicles from small-cell and non–small-cell lung cancer cells

Asparagine-linked glycosylation (N-glycosylation) of proteins in the cancer secretome has been gaining increasing attention as a potential biomarker for cancer detection and diagnosis. Small extracellular vesicles (sEVs) constitute a large part of the cancer secretome, yet little is known about whether their N-glycosylation status reflects known cancer characteristics. Here, we investigated the N-glycosylation of sEVs released from small-cell lung carcinoma (SCLC) and non–small-cell lung carcinoma (NSCLC) cells. We found that the N-glycans of SCLC-sEVs were characterized by the presence of structural units also found in the brain N-glycome, while NSCLC-sEVs were dominated by typical lung-type N-glycans with NSCLC-associated core fucosylation. In addition, lectin-assisted N-glycoproteomics of SCLC-sEVs and NSCLC-sEVs revealed that integrin αV was commonly expressed in sEVs of both cancer cell types, while the epithelium-specific integrin α6β4 heterodimer was selectively expressed in NSCLC-sEVs. Importantly, N-glycomics of the immunopurified integrin α6 from NSCLC-sEVs identified NSCLC-type N-glycans on this integrin subunit. Thus, we conclude that protein N-glycosylation in lung cancer sEVs may potentially reflect the histology of lung cancers.     

Extracellular vesicles: Their functions in plant–pathogen interactions

Extracellular vesicles (EVs) are rounded vesicles enclosed by a lipid bilayer membrane, released by eukaryotic cells and by bacteria. They carry various types of bioactive substances, including nucleic acids, proteins, and lipids. Depending on their cargo, EVs have a variety of well‐studied functions in mammalian systems, including cell‐to‐cell communication, cancer progression, and pathogenesis. In contrast, EVs in plant cells (which have rigid walls) have received very little research attention for many decades. Increasing evidence during the past decade indicates that both plant cells and plant pathogens are able to produce and secrete EVs, and that such EVs play key roles in plant–pathogen interactions. Plant EVs contains small RNAs (sRNAs) and defence‐related proteins, and may be taken up by pathogenic fungi, resulting in reduced virulence. On the other hand, EVs released by gram‐negative bacteria contain a wide variety of effectors and small molecules capable of activating plant immune responses via pattern‐recognition receptor‐ and BRI1‐ASSOCIATED RECEPTOR KINASE‐ and SUPPRESSOR OF BIR1‐mediated signalling pathways, and salicylic acid‐dependent and ‐independent processes. The roles of EVs in plant–pathogen interactions are summarized in this review, with emphasis on important molecules (sRNAs, proteins) present in plant EVs.     

革兰氏阳性菌细胞外囊泡的研究现状

细胞外囊泡(EVs),也称为膜小泡,是真核细胞和细菌分泌的囊泡状小体.它通过携带蛋白质、DNA、RNA和各种代谢物进行细胞间物质的交流传递.根据内容物的不同发挥不同的生理功能,如传递营养物质、参与免疫反应、治疗癌症等.目前大多数研究专注于真核细胞和革兰氏阴性菌囊泡的探索,而对革兰氏阳性菌中分泌的囊泡研究较少.这篇综述总...     

Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases

Mesenchymal stem cells (MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles (EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique anti-inflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.     

Exosomes: endosomal-derived vesicles shipping extracellular messages

Exosomes are membrane vesicles released into the extracellular environment upon exocytic fusion of multivesicular endosomes with the cell surface. They have a particular composition reflecting their origin in endosomes as intraluminal vesicles. In vitro and in vivo studies support the contribution of exosomes to an acellular mode of communication, leading to intercellular transfer of molecules. Exosomes may have regulatory functions in the immune system and their application in cancer immunotherapy is promising. The mechanisms involved in exosome secretion and interaction with target cells are as yet unclear. A better understanding of these mechanisms is also essential to determine the link between exosomes and retroviruses.     

Cancer extracellular vesicles as novel regulators of NK cell response

Natural killer (NK) cells are innate lymphoid cells that play a major role in the immune surveillance against tumors and their activity is regulated through signals derived by a number of NK cell inhibitory and activating receptors as well as cytokines and other soluble factors released in the tumor microenvironment. Extracellular vesicles (EVs) are membrane-enclosed particles secreted by all cell types, both in healthy and diseased conditions, and are important mediators of intercellular communication. Depending on the molecular cargo, tumor-derived extracellular vesicles have the capability to either promote or suppress NK cell-mediated functions.Anti-cancer therapies designed to sustain host anti-tumor immune response represent an appealing strategy to control tumor growth avoiding tumor immune escape. The ability of anticancer chemotherapy to enhance the immunogenic potential of malignant cells mainly relies on the establishment of the immunogenic cell death (ICD) and the release of damage-associated molecular patterns (DAMPs). Moreover, the activation of the DNA damage response (DDR) and the induction of senescence represent two crucial modalities aimed at promoting the clearance of drug-treated tumor cells by NK cells. Herein, we will address the main mechanisms used by cancer-derived extracellular vesicles to modulate NK cell activity, and we will discuss how anti-cancer therapies might impact on the secretion and the immunomodulatory function of these vesicles.     

Manufactured extracellular vesicles as human therapeutics: challenges,advances, and opportunities

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High-impact areas for research and development in the emerging EV biomanufacturing industry.

     

Alterations of long noncoding RNAs and mRNAs in extracellular vesicles derived from the murine heart post‐ischemia–reperfusion injury

Extracellular vesicles (EVs) play important roles in cardiovascular diseases by delivering their RNA cargos. However, the features and possible role of the lncRNAs and mRNAs in cardiac EVs during ischemia–reperfusion (IR) remain unclear. Therefore, we performed RNA sequencing analysis to profile the features of lncRNAs and mRNAs and predicted their potential functions. Here, we demonstrated that the severity of IR injury was significantly correlated with cardiac EV production. RNA sequencing identified 73 significantly differentially expressed (DE) lncRNAs (39 upregulated and 34 downregulated) and 720 DE‐mRNAs (317 upregulated and 403 downregulated). Gene Ontology (GO) and pathway analysis were performed to predict the potential functions of the DE‐lncRNAs and mRNAs. The lncRNA‐miRNA‐mRNA ceRNA network showed the possible functions of DE‐lncRNAs with DE‐mRNAs which are enriched in the pathways of T cell receptor signalling pathway and cell adhesion molecules. Moreover, the expressions of ENSMUST00000146010 and ENSMUST00000180630 were negatively correlated with the severity of IR injury. A significant positive correlation was revealed between TCONS_00010866 expression and the severity of the cardiac injury. These findings revealed the lncRNA and mRNA profiles in the heart derived EVs and provided potential targets and pathways involved in cardiac IR injury.     

Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

Bacterial toxin–antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes.     

Imaging extracellular vesicles: current and emerging methods

Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles released by cells. They range from 30?nm to several micrometers in diameter, and ferry biological cargos such as proteins, lipids, RNAs and DNAs for local and distant intercellular communications. EVs have since been found to play a role in development, as well as in diseases including cancers. To elucidate the roles of EVs, researchers have established different methods to visualize and study their spatiotemporal properties. However, since EV are nanometer-sized, imaging them demands a full understanding of each labeling strategy to ensure accurate monitoring. This review covers current and emerging strategies for EV imaging for prospective studies.     

益生菌胞外囊泡与疾病的相关研究进展

益生菌是对宿主健康有益的活的微生物, 具有广泛的促健康作用。它可以缓解和改善肠道相关炎症性疾病的症状, 降低血清胆固醇, 调节肠道菌群平衡, 对恶性肿瘤的治疗和预防有重要作用。胞外囊泡(extracellular vesicles, EVs)是革兰阴性菌及少数革兰阳性菌释放的含有多种生物活性物质的一种纳米级囊泡结构。EVs通过携带生物信息分子在细菌与细菌或细菌与宿主之间的交流中起着非常重要的作用。虽然近年来研究者们对革兰阳性和阴性病原体来源的EVs的研究越来越多, 但对益生菌产生的EVs的研究却很少。本文综述了近年来益生菌释放的EVs在治疗相关疾病中的研究进展, 并对未来的发展形势进行分析。希望本文能围绕益生菌EVs这一新兴领域的最新进展, 寻找基于EVs的相关疾病的诊断工具和有效治疗方法。