Rats ; Animals ; Astrocytes ; Exosomes/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Biological Transport

Atherosclerosis is a chronic inflammatory disease of vascular walls with a complex etiology. In recent years, the incidence of atherosclerosis continues to increase with obesity and diabetes as major risk factors. As an important metabolic organ in the body, adipose tissue also has a powerful endocrine function. In the case of obesity and diabetes, various cytokines and exosomes derived from adipose tissue mediate organ-organ/cell-cell crosstalk, and are involved in the occurrence and development of various diseases. As an important intercellular communicator, exosomes regulate the pathological process of various cardiovascular diseases and are closely related to atherosclerosis. In this paper, we reviewed the mechanism of adipose-derived exosomes in atherosclerosis with focus on endothelial dysfunction, inflammatory response, lipid metabolism disorder and insulin resistance, hoping to provide reference for the research, diagnosis and treatment of atherosclerosis.
Humans ; Exosomes/metabolism* ; Atherosclerosis ; Obesity/complications* ; Adipose Tissue/metabolism* ; Insulin Resistance

In recent years, mesenchymal stem cell (MSCs)-derived exosomes have attracted much attention in the field of tissue regeneration. Mesenchymal stem cell-derived exosomes are signaling molecules for communication among cells. They are characterized by natural targeting and low immunogenicity, and are mostly absorbed by cells through the paracrine pathway of mesenchymal stem cells. Moreover, they participate in the regulation and promotion of cell or tissue regeneration. As a scaffold material in regenerative medicine, hydrogel has good biocompatibility and degradability. Combining the two compounds can not only improve the retention time of exosomes at the lesion site, but also improve the dose of exosomes reaching the lesion site by in situ injection, and the therapeutic effect in the lesion area is significant and continuous. This paper summarizes the research results of the interaction of exocrine and hydrogel composite materials to promote tissue repair and regeneration, in order to facilitate research in the field of tissue regeneration in the future.
Hydrogels/metabolism* ; Exosomes/metabolism* ; Wound Healing ; Regenerative Medicine ; Mesenchymal Stem Cells/metabolism*

Patients with glioblastoma (GBM) generally have a bad prognosis and short overall survival after being treated with surgery, chemotherapy or radiotherapy due to the histological heterogeneity, strong invasive ability and rapid postoperative recurrence of GBM. The components of GBM cell-derived exosome (GBM-exo) can regulate the proliferation and migration of GBM cell via cytokines, miRNAs, DNA molecules and proteins, promote the angiogenesis via angiogenic proteins and non-coding RNAs, mediate tumor immune evasion by targeting immune checkpoints with regulatory factors, proteins and drugs, and reduce drug resistance of GBM cells through non-coding RNAs. GBM-exo is expected to be an important target for the personalized treatment of GBM and a marker for diagnosis and prognosis of this kind of disease. This review summarizes the preparation methods, biological characteristics, functions and molecular mechanisms of GBM-exo on cell proliferation, angiogenesis, immune evasion and drug resistance of GBM to facilitate developing new strategies for the diagnosis and treatment of GBM.
Humans ; Glioblastoma/genetics* ; Exosomes/metabolism* ; MicroRNAs/metabolism* ; Prognosis ; Cell Proliferation ; Brain Neoplasms/genetics* ; Cell Line, Tumor

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100β was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 μg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×10¹² particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100β,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 μg/ml promoted the proliferation of SCs,and that of 40 μg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.
Humans ; Rats ; Animals ; Exosomes/metabolism* ; Platelet-Rich Plasma ; Schwann Cells ; Coculture Techniques ; Cell Proliferation ; Cells, Cultured

Objective To investigate the effects of natural killer (NK)-cell-derived miR-30e-3p-containing exosomes (Exo) on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis and invasion. Methods NK cells were isolated and amplified from the peripheral blood of healthy donors, and NK cell-derived Exo was isolated and identified, which were further co-cultured with NEC cells and were randomly grouped into Exo1 and Exo2 groups. Transmission electron microscopy (TEM) was used to observe the morphology and size of exosomes. Western blot analysis was used to detect the expression levels of exosome markers apoptosis related gene 2- interacting protein X(ALIX), tumor susceptibility gene 101(TSG101), CD81 and calnexin. The NC plasmids, mimics and inhibitors of miR030e-3p were respectively delivered into the NK cells, and the corresponding NK cells-derived Exo were co-cultured with NEC cells, which were divided into NC, Exo, mimic and inhibitor groups. CCK-8 assay was used to evaluate cell proliferation, flow cytometry was conducted to determine cell cycle, annexin V-FITC/PI double staining was employed to detect cell apoptosis, and Transwell^TM assay was performed to detect cell invasion abilities. Real-time quantitative PCR was used to detect the expression of miR-23b, miR-422a, miR-133b, miR-124, miR-30e-3p and miR-99a in NCE cells and exosomes. Results The percentages of CD56⁺CD3⁺ cells and CD56⁺CD16⁺ cells in NK cells were (0.071±0.008)% and (90.6±10.6)%, respectively. Exosome isolated from NK cells ranged from 30 nm to 150 nm, and was positive for ALIX, TSG101 and CD81, while negative for calnexin. NK cell-derived Exos inhibited the proliferation, reduced the proportion of S-phase cells and the number of invaded cells of NEC cells, and promoted the apoptosis and the proportion of G1 phase cells. Overexpression of miR-30E-3p in NK cell-derived exosome inhibited the proliferation and invasion of NEC cells, and blocked cell cycle and promoted apoptosis, while knockdown miR-30e-3p in NK cell-derived exosomes did the opposite. Conclusion miR-30e-3p in NK cell-derived exosomes can inhibit the proliferation and invasion of ESCC cells, block their cell cycle and induce their apoptosis.
Humans ; Esophageal Squamous Cell Carcinoma/genetics* ; Esophageal Neoplasms/genetics* ; Exosomes/metabolism* ; Calnexin/metabolism* ; Cell Movement/genetics* ; MicroRNAs/metabolism* ; Cell Proliferation/genetics* ; Killer Cells, Natural ; Cell Line, Tumor ; Apoptosis/genetics*

Objective To investigate the effect of viral myocarditis serum exosomal miR-320 on apoptosis of cardiomyocytes and its mechanism. Methods The model of viral myocarditis mice was established by intraperitoneal injection of Coxsackie virus B3. Serum exosomes were extracted by serum exosome extraction kit and co-cultured with cardiomyocytes. The uptake of exosomes by cardiomyocytes was detected by laser confocal microscopy. Cardiomyocytes were transfected with miR-320 inhibitor or mimic, and the expression level of miR-320 was detected by real-time quantitative PCR. Flow cytometry was used to detect cardiomyocyte apoptosis rate, and the expression levels of B cell lymphoma 2 (Bcl2) and Bcl2-related X protein (BAX) were tested by Western blot analysis. The prediction of miR-320 target genes and GO and KEGG enrichment analysis were tested by online database. The relationship between miR-320 and its target gene phosphoinositide-3-kinase regulatory subunit 1(Pik3r1) was examined by luciferase reporter gene. The effect of miR-320 on AKT/mTOR pathway protein was detected by Western blot analysis. Results Viral myocarditis serum exosomes promoted cardiomyocyte apoptosis, and increased the level of BAX while the level of Bcl2 was decreased. miR-320 was significantly up-regulated in myocardial tissue of viral myocarditis mice, and both pri-miR-320 and mature of miR-320 were up-regulated greatly in cardiomyocytes. The level of miR-320 in cardiomyocytes treated with viral myocarditis serum exosomes was significantly up-regulated, while transfection of miR-320 inhibitor counteracted miR-320 overexpression and reduced apoptosis rate caused by exosomes. Pik3r1 is the target gene of miR-320, and its overexpression reversed cardiomyocyte apoptosis induced by miR-320 up-regulation. The overexpression of miR-320 inhibited AKT/mTOR pathway activation. Conclusion Viral myocarditis serum exosome-derived miR-320 promotes apoptosis of mouse cardiomyocytes by inhibiting AKT/mTOR pathway by targeting Pik3r1.
Mice ; Animals ; Myocytes, Cardiac ; Phosphatidylinositol 3-Kinase/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Myocarditis/pathology* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; MicroRNAs/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis/genetics*

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Humans ; Male ; Mice ; Animals ; Orchitis ; Uropathogenic Escherichia coli/metabolism* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Macrophages/metabolism* ; Phenotype ; Infertility, Male/metabolism*

OBJECTIVE: To explore the expression level of exosome derived miR-181b-5p in different disease stages of children with acute lymphoblastic leukemia and its relationship with clinical characteristics. METHODS: Bone marrow plasma samples of 86 children with ALL were collected. Exosomes were extracted by exosome extraction kit, and RNA in exosomes was extracted by TRIzol method. The levels of miR-181b-5p in the blood plasma exosomes of the patients in the newly diagnosed group, relapse group, remission group and control group were detected by qRT- PCR. The difference of miR-181b-5p expression level in each group was compared and analyzed, and the relationship between miR-181b-5p expression level and clinical characteristics was analyzed. RESULTS: The expression level of exosomal miR-181b-5p in the newly diagnosed group and the relapsed group was significantly lower than that in the remission group and the control group (P< 0.05). The expression level of exosomal miR-181b-5p in T-ALL children was higher than that in B-ALL children (P<0.05). The expression level of plasma exosomal miR-181b-5p in male children was higher than that in female children (P<0.01). CONCLUSION Exosome derived miR-181b-5p changes dynamically in the course of ALL children, and can be used as a marker miRNA to monitor disease status. Exosomes can transmit information in the tumor microenvironment and serve as a potential carrier for biomolecular targeted therapy.
Humans ; Male ; Female ; Child ; Exosomes/metabolism* ; Clinical Relevance ; MicroRNAs/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Tumor Microenvironment

Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.
Humans ; Exosomes/metabolism* ; Drug Carriers/metabolism* ; Pancreatic Neoplasms/diagnosis* ; Antineoplastic Agents/therapeutic use*