Research progress of mesenchymal stem cell-derived extracellular vesicles in liver diseases / 中华肝脏病杂志

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) transport and transmit intercellular information and play an essential role in physiological and pathological processes. MSC-EVs, MSC-EVs-microRNA, and genetically modified MSC-EVs are involved in the onset and progression of different liver diseases and play a role in reducing liver cell damage, promoting liver cell regeneration, inhibiting liver fibrosis, regulating liver immunity, alleviating liver oxidative stress, inhibiting liver cancer occurrence, and others. Hence, it will replace MSCs as a research hotspot for cell-free therapy. This article reviews the research progress of MSC-EVs in liver diseases and provides a new basis for cell-free therapy of clinical liver diseases.

Research progress in role of exosomes exosomes in mental disorders / 中南大学学报(医学版)

Exosomes are a class of extracellular vesicles with a structure of lipid bilayer-membrane. In the central nervous system (CNS), exosomes can be secreted from both neurons and glial cells. Exosomes released into the extracellular matrix can freely cross the blood-brain barrier and function as crucial carriers of cellular communication and substance exchange in the CNS. Exosomes play a key role in the pathological process of mental disorders such as schizophrenia, depression, and bipolar disorder, and they have the potential to be used as a targeted carrier of antipsychotic medications. Exosomes are likely to become a new tool in the future to aid in the early prevention, accurate diagnosis, and effective treatment for people with mental disorders.

Research advances on the mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis / 中华烧伤杂志

Wound healing involves complex pathophysiological mechanism, among which angiogenesis is considered as one of the key steps in wound healing, and promoting wound angiogenesis can accelerate wound healing. In recent years, mesenchymal stem cell-derived extracellular vesicles have been proven to produce equivalent effects of wound healing promotion comparable to stem cell therapy, with the advantages of low antigenicity and high biocompatibility. The specific mechanism by which extracellular vesicles facilitate wound healing is still not fully understood and is thought to involve all stages of wound healing. This article focuses on the possible mechanism of extracellular vesicles of adipose-derived mesenchymal stem cells in promoting wound angiogenesis, so as to provide ideas for further study on the mechanism of extracellular vesicles to promote wound healing.

MSCs-derived apoptotic extracellular vesicles promote muscle regeneration by inducing Pannexin 1 channel-dependent creatine release by myoblasts / 国际口腔科学杂志·英文版

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.

Estudo das vesículas extracelulares de Toxoplasma gondii e a correlação com o sistema imune de hospedeiros infectados / Study of extracellular vesicles of Toxoplasma gondii and the correlation with the immune system of infected hosts

As vesículas extracelulares (EVs) são nanopartículas produzidas e liberadas por células eucarióticas e procarióticas com propriedades biológicas. EVs desempenham um papel importante no sistema imunológico, transporte de moléculas e comunicação celular. A fim de compreender a participação das EVs na resposta imune durante a infecção por Toxoplasma gondii, este estudo teve com objetivo, investigar as respostas humoral e celular, em camundongos imunizados com EVs liberadas por taquizoítos e desafiados com T. gondii. As EVs de T. gondii (EVs-toxo) foram purificadas a partir de taquizoítos mantidos em culturas celulares. A seguir, um grupo de camundongos foi imunizado com as EVs-toxo e Alum como adjuvante (EV-IM). Como controles, o grupo negativo (N) recebeu somente Alum e os camundongos do grupo positivo (CHR) foram infectados com a cepa ME-49. O grupo EV-IM apresentou altos níveis de IgG1 do que IgM ou IgG2a. IgGs purificadas de soros destes camundongos foram capazes de opsonizar taquizoítos (cepa RH) e, quando os camundongos foram desafiados com a cepa RH tiveram a mortalidade atrasada em 48h. Células do cérebro e do baço deste grupo expressaram mais IFN-y, IL-10 e TNF-α. As EVs dos soros destes camundongos foram purificadas por ultracentrifugação. As análises das EVs de camundongo (EVs-mouse) mostraram que as concentrações de EVs liberadas de soros do grupo N foram menores que as do grupo EV-IM e a presença de exossomos foi confirmada pelo immunoblot das EVs. Esplenócitos de camundongos foram estimulados com EVs-toxo. Esplenócitos dos camundongos do grupo EV-IM expressaram mais IFN-y; TNF-α e IL-17, que os do grupo N. Curiosamente, a IL-10 foi altamente expressa apenas em esplenócitos do grupo EV-IM. Os resultados da expressão gênica de microRNAs (miRNAs) mostraram que os camundongos do grupo EV-IM expressaram mais miR-155-5p, miR-29c-3p e miR-125b-5p do que os do grupo N. Todos esses dados sugerem a participação das EVs na interação T. gondii-hospedeiro. Além disso, os miRNAs liberados pelas EVs interagem com a modulação da resposta imune celular anti T. gondii. A imunização com EVs foi capaz de induzir proteção imunológica. Esses dados fornecem subsídios para propor a diferenciação entre hospedeiros infectados e não infectados pela concentração de EVs. (AU)

Extracellular vesicles (EVs) are nanoparticles produced and released by eukaryotic and prokaryotic cells with biological properties. EVs play an important role in the immune system, transport of molecules and cellular communication. In order to understand the participation of EVs in the immune response during Toxoplasma gondii infection, this study aimed to investigate the humoral and cellular responses in mice immunized with EVs released by tachyzoites and challenged with T. gondii. T. gondii EVs (toxo-EVs) were purified from tachyzoites maintained in cell cultures. Then, a group of mice was immunized with EVs-toxo and Alum as an adjuvant (EV-IM). As controls, the negative group (N) received only Alum and the mice in the positive group (CHR) were infected with strain ME-49. The EV-IM group had higher levels of IgG1 than IgM or IgG2a. IgGs purified from the sera of these mice were able to opsonize tachyzoites (RH strain) and, when mice were challenged with the RH strain, mortality was delayed by 48h. Brain and spleen cells from this group expressed more IFN-γ, IL-10 and TNF-α. The EVs from the sera of these mice were purified by ultracentrifugation. Analysis of mouse EVs (mouse EVs) showed that the concentrations of EVs released from sera from the N group were lower than those from the EV-IM group and the presence of exosomes was confirmed by the immunoblot of EVs. Mouse splenocytes were stimulated with EVs-toxo. Splenocytes from EV-IM group mice expressed more IFN-y; TNF-α and IL-17 than those of the N group. Interestingly, IL-10 was highly expressed only in splenocytes of the EV-IM group. The results of gene expression of microRNAs (miRNAs) showed that mice in the EV-IM group expressed more miR-155-5p, miR-29c-3p and miR-125b-5p than those in the N group. participation of EVs in T. gondii host interaction. Furthermore, miRNAs released by EVs interact with the modulation of the cellular immune response against T. gondii. Immunization with EVs was able to induce immune protection. These data provide subsidies to propose the differentiation between infected and uninfected hosts by the concentration of EVs. (AU)

Extracellular signals regulate the biogenesis of extracellular vesicles

Extracellular vesicles (EVs) are naturally released membrane vesicles that act as carriers of proteins and RNAs for intercellular communication. With various biomolecules and specific ligands, EV has represented a novel form of information transfer, which possesses extremely outstanding efficiency and specificity compared to the classical signal transduction. In addition, EV has extended the concept of signal transduction to intercellular aspect by working as the collection of extracellular information. Therefore, the functions of EVs have been extensively characterized and EVs exhibit an exciting prospect for clinical applications. However, the biogenesis of EVs and, in particular, the regulation of this process by extracellular signals, which are essential to conduct further studies and support optimal utility, remain unclear. Here, we review the current understanding of the biogenesis of EVs, focus on the regulation of this process by extracellular signals and discuss their therapeutic value.

Research advances on mesenchymal stem cell-derived extracellular vesicles in promoting angiogenesis of diabetic ulcers / 中华烧伤杂志

Extracellular vesicles are nanoparticles secreted by most eukaryotic cells and play important roles in material transport and information transmission between cells, involved in inflammation, angiogenesis, antigen presentation, cell apoptosis, cell differentiation, and other biological processes. The culture supernatant of mesenchymal stem cells is rich in extracellular vesicles, and the extracellular vesicles can regulate the formation of new blood vessels, a key step in wound healing and tissue repair. The persistence of diabetic ulcers is closely related to the blocked formation of wound vascular network. This article reviews the role of extracellular vesicles derived from mesenchymal stem cells in promoting angiogenesis of diabetic ulcers, in order to provide a new idea for the treatment of diabetic ulcers.

Cancer cells corrupt normal epithelial cells through miR-let-7c-rich small extracellular vesicle-mediated downregulation of p53/PTEN / 国际口腔科学杂志·英文版

Tumor volume increases continuously in the advanced stage, and aside from the self-renewal of tumor cells, whether the oncogenic transformation of surrounding normal cells is involved in this process is currently unclear. Here, we show that oral squamous cell carcinoma (OSCC)-derived small extracellular vesicles (sEVs) promote the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of normal epithelial cells but delay their apoptosis. In addition, nuclear-cytoplasmic invaginations and multiple nucleoli are observed in sEV-treated normal cells, both of which are typical characteristics of premalignant lesions of OSCC. Mechanistically, miR-let-7c in OSCC-derived sEVs is transferred to normal epithelial cells, leading to the transcriptional inhibition of p53 and inactivation of the p53/PTEN pathway. In summary, we demonstrate that OSCC-derived sEVs promote the precancerous transformation of normal epithelial cells, in which the miR-let-7c/p53/PTEN pathway plays an important role. Our findings reveal that cancer cells can corrupt normal epithelial cells through sEVs, which provides new insight into the progression of OSCC.

Research Progress on Immunomodulatory Activity and Clinical Application of Mesenchymal Stem Cells-Derived Extracellular Vesicles--Review / 中国实验血液学杂志

Mesenchymal stem cells (MSC) have been widely used in tissue regeneration and treatment graft versus host disease (GVHD) and immune diseases due to their self-renewal, multi-differentiation and immunoregulatory potential. However, more and more scholars begin to put weight on the MSC -derived extracellular vesicles (MSC-EV) for its regulation of inflammation and immunity. MSC-EV can activate the relevant signal pathways and regulate the function and biological behaviors of cells via acting on target cells and mediating communication between cells. MSC-EV has important potential clinical applications for its powerful immunomodulatory and hematopoietic regulatory functions. It is considered as a potential therapeutic tool to treat autoimmune diseases and GVHD. This paper reviewed the immunomodulatory activity of MSC-EV as well as the research progress of MSC-EV in hematopoietic stem cell transplantation, and discussed its potential clinical applications in the future.

The extracellular vesicles from gram-positive bacteria: a review / 生物工程学报

Extracellular vesicles (EVs), also known as membrane vesicles, are vesicular bodies secreted by eukaryotic cells and bacteria. EVs can carry proteins, DNA, RNA, and various metabolites for the exchange and transmission of substances between cells. They play contents-dependent physiological functions, such as delivering nutrients, participating in immune response, and treating cancers. Currently, most studies focus on the exploration of vesicles secreted by eukaryotic cells and gram-negative bacteria, while few studies focus on gram-positive bacteria. This review summarized the production, content composition, physiological function, and engineering of EVs secreted by gram-positive bacteria, and prospected future perspectives in this area.

Research progress of extracellular vesicles in the treatment of renal disease / 生理学报

Extracellular vesicles (EVs) are lipid bilayer-enclosed structures containing diverse bioactive cargoes that play a major role in intercellular communication in both physiological and pathological conditions. Currently, the field of EV-based therapy has been rapidly growing, and two main therapeutic uses of EVs can be surmised: (i) exploiting stem cell-derived EVs as therapeutic agents; and (ii) employing EVs as natural therapeutic vectors for drug delivery. This review will discuss the recent advances in EV-based therapy in the treatment of renal disease.

Dental stem cell-derived extracellular vesicles as promising therapeutic agents in the treatment of diseases / 国际口腔科学杂志·英文版

Dental stem cells (DSCs), an important source of mesenchymal stem cells (MSCs), can be easily obtained by minimally invasive procedures and have been used for the treatment of various diseases. Classic paradigm attributed the mechanism of their therapeutic action to direct cell differentiation after targeted migration, while contemporary insights into indirect paracrine effect opened new avenues for the mystery of their actual low engraftment and differentiation ability in vivo. As critical paracrine effectors, DSC-derived extracellular vesicles (DSC-EVs) are being increasingly linked to the positive effects of DSCs by an evolving body of in vivo studies. Carrying bioactive contents and presenting therapeutic potential in certain diseases, DSC-EVs have been introduced as promising treatments. Here, we systematically review the latest in vivo evidence that supports the therapeutic effects of DSC-EVs with mechanistic studies. In addition, current challenges and future directions for the clinical translation of DSC-EVs are also highlighted to call for more attentions to the (I) distinguishing features of DSC-EVs compared with other types of MSC-EVs, (II) heterogeneity among different subtypes of DSC-derived EVs, (III) action modes of DSC-EVs, (IV) standardization for eligible DSC-EVs and (V) safety guarantee for the clinical application of DSC-EVs. The present review would provide valuable insights into the emerging opportunities of DSC-EVs in future clinical applications.

Retos y oportunidades en el estudio de vesículas extracelulares: contexto institucional a nivel mundial y situación actual en Colombia / Challenges and opportunities in the study of extracellular vesicles: Global institutional context and national state of the art

Resumen En la última década se ha incrementado el número de estudios y publicaciones sobre las vesículas extracelulares y los exosomas. En Colombia, ha habido interés y avances en su estudio, lo que se evidencia en el aumento de publicaciones y proyectos de investigación. Sin embargo, este es un campo de investigación aún en desarrollo, con desafíos analíticos y limitaciones técnicas, por lo cual, en el planteamiento de los proyectos de investigación y desarrollo, es necesario considerar cuál es el estado del campo científico a nivel mundial en cuanto a la nomenclatura y la clasificación de las vesículas extracelulares, las técnicas, recursos, requisitos y especificaciones de calidad y las instituciones que regulan el campo. La respuesta a esta pregunta permitirá desarrollar estudios que cumplan con los estándares internacionales, y las exigencias y recomendaciones institucionales. Sin embargo, la información científica disponible se encuentra dispersa y no todos los aspectos son tratados a cabalidad. En este actualización se condensa la información disponible y se presentan los términos oficiales para denominar las vesículas extracelulares y la nomenclatura aceptada actualmente, así como la evolución del campo, la homogenización de los parámetros experimentales, el establecimiento de autoridades científicas, instituciones y recursos, y las recomendaciones que se han generado a nivel mundial para el desarrollo de investigaciones en vesículas extracelulares, incluidos su aislamiento, caracterización y estudio funcional. Por último, se analiza el contexto nacional de una forma crítica, teniendo en cuenta las fortalezas institucionales, los errores usualmente cometidos, y las técnicas y tecnologías analíticas disponibles.

Abstract In the last decade, the number of studies and publications on extracellular vesicles (EV) and exosomes has boomed. Colombia has displayed interest and progress in their study as shown in the increase of research project publications and products. However, this research field is still developing and has its own analytical challenges and technical limitations. For planning research projects and developing EV studies it is necessary to consider what is the state of the scientific field worldwide concerning EV nomenclature and classification, available techniques, resources, requirements and quality specifications, and the institutions that regulate the field. Answering this question will elicit EV studies that comply with international standards and respond to institutional demands and recommendations. However, the scientific information available is scattered and not all the aspects are considered in full. In this update, the available information is condensed and the official terms and currently defined nomenclature is presented, as well as the evolution of the field, the homogenization of the experimental parameters, the establishment of scientific authorities, institutions, and resources, and the recommendations generated worldwide for their development and research including their isolation, characterization, and functional studies. Finally, I analyzed the national context in a critical way, considering institutional strengths, common mistakes, and available analytical techniques and technologies.

Bases inmunológicas de la enfermedad neumocócica y el candidato vacunal PVC7-TT / Immunological bases of pneumococcal disease and vaccine candidate PVC7-TT

Introducción: Las enfermedades infecciosas del tracto respiratorio se encuentran entre las primeras causas de entidades respiratorias en edades extremas de la vida. Objetivo: Describir las bases inmunológicas de la enfermedad y el nuevo candidato vacunal conjugado antineumocócico PCV7-TT desarrollado en Cuba. Métodos: Se realizó una búsqueda en las bases de datos Medline, Pubmed, SciELO, LILACS, Cochrane Library y Web of Science, de documentos publicados entre mayo del 2018 y marzo del 2020. Se seleccionaron los 64 artículos de mayor relevancia y novedad. Resultados: Streptococcus pneumoniae es el agente etiológico de la enfermedad neumocócica; se le atribuye alrededor de un millón de defunciones anuales, principalmente en países en vías de desarrollo. Es un coco Gram-positivo, anaerobio facultativo y encapsulado que se encuentra dividido en 48 serogrupos y 97 serotipos tipificados. Presenta varios factores de virulencia que garantizan su mecanismo de patogenicidad; uno de los más importantes es el polisacárido capsular que constituye la diana de las vacunas antineumocócicas conjugadas y no conjugadas existentes. En el presente artículo se consideró la proteína de superficie C del neumococo como un posible candidato en la investigación y desarrollo de vacunas preventivas. Asimismo, las vesículas extracelulares podría ser un posible candidato para adyuvante vacunal con fines preventivos y terapéuticos. Conclusiones: El neumococo es un problema de salud a nivel global y el uso de vacunas conjugadas antineumocócicas constituye la herramienta más eficaz para su prevención. El candidato vacunal PCV7-TT desarrollado en Cuba es seguro, bien tolerado, inmunogénico y no inferior a las vacunas actualmente registradas(AU)

Introduction: Infectious diseases of the respiratory tract are among the leading causes of respiratory conditions in patients at extreme ages. Objective: Describe the immunological bases of the disease and the new conjugate pneumococcal vaccine candidate PCV7-TT developed in Cuba. Methods: A search was conducted in the databases Medline, Pubmed, SciELO, LILACS, Cochrane Library and Web of Science for documents published from May 2018 to March 2020. The 64 most relevant and novel papers were selected. Results: Streptococcus pneumoniae is the causative agent of pneumococcal disease, a condition causing about one million deaths a year worldwide, mainly in developing countries. It is a Gram-positive facultative anaerobic encapsulated coccus divided into 48 serogroups and 97 typified serotypes. Several virulence factors ensure its pathogenicity mechanism. One of the most important of these is the capsular polysaccharide constituting the target of the existing conjugate and non-conjugate pneumococcal vaccines. The study considered pneumococcal surface protein C as a possible candidate for the research and development of preventive vaccines. On the other hand, extracellular vesicles could be a possible vaccine adjuvant candidate for preventive and therapeutic use. Conclusions: Pneumococcus is a global health problem, and the use of conjugate pneumococcal vaccines is the most effective tool for its prevention. The vaccine candidate PCV7-TT developed in Cuba is safe, well-tolerated, immunogenic and not inferior to the vaccines so far registered(AU)

BM-MSC-derived small extracellular vesicles (sEV) from trained animals presented nephroprotective potential in unilateralureteral obstruction model

Background: The efficacy of bone marrow mesenchymal stromal cells (BM-MSC) and its extracellular vesicles has been demonstrated for a broad spectrum of indications, including kidney diseases. However, BM-MSC donor characteristics and their potential are not usually considered. Therefore, the present work aims to evaluate the nephroprotective capacity of sEV secreted by BM-MSC from trained rats inunilateral ureteral obstruction (UUO) model. Methods: BM-MSC was characterized by their differentiation potential and immunophenotypic markers. The sEV were isolated by ultracentrifugation and characterized by nanoparticle tracking analysis and western blot. Its miRNA cargo was examined by quantitative PCR analysis for miR-26a, 126a, and 296. Wistar rats were submitted to UUO procedure and concomitantly treated with sEV secreted by BM-MSC from the untrained andtrained rats. The kidney tissue from all groups was evaluated for fibrosis mediators (transforming growth factor beta1 and collagen), CD34-angiogenesis marker, and hypoxia-inducible factor 1 alpha (HIF-1α). Results: Treadmill training stimulated in BM-MSC the production of sEV loaded with pro-angiogenic miR-296. The treatment with this sEVin UUO-rats was able to attenuate collagen accumulation and increase CD34 and HIF-1α in the kidney tissue when compared to untrained ones. Tubular proximal cells under hypoxia and exposed to BM-MSC sEV demonstrate accumulation in HIF-1α and NFR-2 (nuclear factor erythroid 2-related factor 2), possibly to mediate the response to hypoxia and oxidative stress, under these conditions. Conclusion: The BM-MSC sEV from trained animals presented an increased nephroprotective potential compared to untrained vesicles by carrying 296-angiomiR and contributing to angiogenesis in UUO model.(AU)

Estudo das vesículas extracelulares de Toxoplasma gondii e a correlação com a infecção humana / Study of the extracellular vesicles of Toxoplasma gondii and the correlation with human infection

Toxoplasma gondii é causador da toxoplasmose, uma das doenças mais prevalentes no mundo. Estudos recentes mostraram que vesículas extracelulares (EVs) liberadas por parasitas participam no processo de invasão e replicação no hospedeiro, porém o mecanismo de infecção ainda não está completamente elucidado. O objetivo desse trabalho foi identificar e caracterizar EVs produzidas por taquizoítos das cepas RH, ME-49 e VEG de T. gondii e a participação na patogênese da toxoplasmose. Purificação de EVs liberadas das três cepas de T. gondii foi realizada por cromatografia de exclusão de tamanho seguida por ELISA. Concentração e tamanho das vesículas isoladas foram analisados por Nanoparticle Tracking Analysis, o qual mostrou que as três cepas possuem perfis de liberação de EVs similares, com maior produção observada pela cepa RH. Quando analisados diferentes tempos de incubação, observou-se que em 2 horas de incubação ocorreu maior liberação de EVs do que em 24 horas de incubação, para as três cepas. A maior parte das vesículas encontradas possuía tamanho entre 100-200 nm, caracterizadas como microvesículas. Observou-se através de imagens capturadas por Microscopia Eletrônica de Varredura que a cepa RH liberou mais EVs do que as cepas VEG e ME-49. Após a análise de taquizoítos da cepa RH por Microscopia Eletrônica de Transmissão, observou-se que no...(AU)

Toxoplasma gondii is the agent of toxoplasmosis, one of the most prevalent diseases in the world. Recent studies show that extracellular vesicles (EVs) released by parasites are involved in the invasion and replication mechanisms in the host, however they are not completely clear. The aim of this study was to identify and characterize EVs released by tachyzoites from RH, ME-49 and VEG strains of T. gondii and their role in toxoplasmosis pathogenesis. EVs purification was performed by size exclusion chromatography followed by ELISA. Size and concentration of EVs was analysed by Nanoparticle Tracking Analysis, which showed similar EVs release profile from the three strains, however RH strain showed higher production of EVs. When analysed different incubation periods, it was observed higher production of EVs in 2 hours rather than 24 hours of incubation, for the three strains. The majority size of EVs found was of 100-200 nm which is classified by microvesicles. Images captured by Scanning Electron Microscopy showed that tachyzoites from RH strain released more EVs than tachyzoites from ME-49 and VEG strains. Also, images captured by Transmission Electron Microscopy of tachyzoites from RH strain showed that in the beginning of incubation period starts the formation of multivesicular bodies with vesicles inside ready to be released in the lumen. After 24 hours, it was able to observe intense release of EVs from the plasmatic membrane, as well as from posterior pore and apical ring. Furthermore, it was found that T. gondii was able to express the same miRNAs found in infected hosts. miR-155-5p, miR-125b-5p e miR-423-3p were the most expressed in tachyzoites as well as in EVs released from them in the three strains. Experiments with laboratory mice infected with tachyzoites of RH strain mixed with EVs, especially for EVs released from RH strain, showed that EVs can enhance parasitemia and virulence, decreasing mice's survival. Protein extracted from EVs of the three strains demonstrated similar electrophoretic profiles, but when EVs were incubated with sera from patients with toxoplasmosis, in Immunoblot analysis, EVs from ME-49 and VEG strains reacted poorly, unlike EVs from RH strains which reacted with sera from patients with gestational and cerebral toxoplasmosis. Stimulus of EVs released form the three strains in mice splenocytes in vitro produced similar concentrations of IL-10 and IFN- after 24 and 48 hours, in the three strains. EVs released from RH strain stimulated the production of more TNF- than EVs released from ME-49 and VEG strains. Finally, these results suggest that EVs released from tachyzoites of three T. gondii strains, especially the ones released from RH strain, were able to stablish communication between host cells and parasites, modulating host immune system, although they unbalance the host immune response since they carry virulence factors. (AU)

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Overexpression of serum extracellular vesicle microRNA-215-5p is associated with early tumor recurrence and poor prognosis of gastric cancer

OBJECTIVES: Extracellular vesicle microRNAs (EV-miRNAs) have been demonstrated to be reliable candidate biomarkers for clinical applications. However, the clinical application potential of serum EV-miR-215-5p for gastric cancer (GC) remains poorly understood. The goal of our study was to determine the efficacy of serum EV-miR-215-5p in predicting the prognosis of GC. METHODS: Blood samples were collected from 118 patients with GC, 60 patients with benign gastric disease and BGD and 70 healthy controls. The relative levels of serum EV-miR-215-5p were measured using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Compared to patients with BGD and normal controls, GC patients exhibited remarkably higher serum EV-miR-215-5p level, especially those with early tumor recurrence (ETR). Receiver operating characteristic (ROC) curve analysis showed that serum EV-miR-215-5p was able to distinguish GC patients from BGD patients or healthy controls and GC patients with ETR from those without ETR. In addition, increased serum EV-miR-215-5p levels were notably correlated with invasive depth, TNM stage, and lymph node metastasis. Moreover, serum EV-miR-215-5p levels were greatly decreased after surgical treatment, but increased at the time of ETR. Survival analysis showed that patients with higher serum EV-miR-215-5p had shorter survival. Furthermore, serum EV-miR-215-5p was an independent risk factor for GC. CONCLUSIONS: Serum EV-miR-215-5p might be a novel biomarker for predicting ETR and prognosis of GC.

Human Serum-derived Extracellular Vesicles Protect A549 from PM / 生物医学与环境科学（英文）

Objective@#Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM @*Methods@#EVs were isolated from the serum of healthy subjects, quantified @*Results@#PM @*Conclusions@#EVs treatment promotes cell survival and attenuates PM

Effect of exosome / 中南大学学报(医学版)

Traumatic brain injury (TBI) is a main cause of death and disability worldwide, posing a serious threat to public health. But currently, the diagnosis and treatments for TBI are still very limited. Exosomes are a group of extracellular vesicles and participate in multiple physiological processes including intercellular communication and substance transport. Non-coding RNAs (ncRNA) are of great abundancy as cargo of exosomes. Previous studies have shown that ncRNAs are involved in several pathophysiological processes of TBI. However, the concrete mechanisms involved in the effects induced by exosome-derived ncRNA remain largely unknown. As an important component of exosomes, ncRNA is of great significance for diagnosis, precise treatment, response evaluation, prognosis prediction, and complication management after TBI.