Research progress of exosomes in the diagnosis and treatment of sepsis / 中华危重病急救医学

Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.

Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling / 国际口腔科学杂志·英文版

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.

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.

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.

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.

Vesículas extracelulares como predictores tempranos de diabetes gestacional / Extracellular vesicle concentration in maternal plasma as an early marker of gestational diabetes

Background During pregnancy, there is an increase in the amount of extracellular vesicles, especially placental exosomes, in maternal plasma. Aim To isolate and characterize extracellular vesicles from blood during the three trimesters of pregnancy and to evaluate their capacity to identify patients at risk of developing gestational diabetes. Material and Methods A case-control study was conducted in a cohort of 50 pregnant women with plasma samples taken in each trimester. Six women who developed gestational diabetes were paired with three healthy controls per case (a total of 19). Clinical characteristics were recorded at first prenatal appointment, and blood samples were obtained during the first, second and third trimesters. Extracellular vesicles were isolated from plasma by the commercial kit, ExoQuick™. Nanoparticle tracking analysis, was used to characterize the obtained extracellular vesicles. Results The total concentration of extracellular particles isolated from maternal plasma increased along with gestational age. The size of the extracellular vesicles obtained in the first trimester of pregnancy was very similar between groups (144 ± 37 nm for controls and 143 ± 34 nm for patients with gestational diabetes mellitus). Moreover, the concentration of extracellular vesicles collected in the first trimester, was significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (7.94 x 10 8 and 5.15 x 10 8 , p = 0.03). Conclusions Our results provide an insight into the potential capacity of first trimester plasma extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus.