Acute kidney injury (AKI) is characterized by a sudden and rapid decline of renal function and associated with high morbidity and mortality. AKI can be caused by various factors, and ischemia-reperfusion injury (IRI) is one of the most common causes of AKI. An increasing number of studies found out that exosomes of mesenchymal stem cells (MSCs) could alleviate IRI-AKI by the adjustment of the immune response, the suppression of oxidative stress, the reduction of cell apoptosis, and the promotion of tissue regeneration. This article summarizes the effect and mechanism of MSC-derived exosomes in the treatment of renal ischemia-reperfusion injury, in order to provide useful information for the researches on this field.
ObjectiveTo understand the research progress of related biomarkers in early diagnosis of gastric cancer in recent years.MethodThe domestic and foregin literatures on studies of biomarkers of early diagnosis of gastric cancer in recent years were reviewed.ResultsAt present, the sensitivity and specificity of serum tumor biomarkers of gastric cancer such as CEA and CA19-9 were lower, so the molecular markers that could predict, screen, and diagnose gastric cancer in the early stage were further explored. The recent studies suggested that microRNAs, long non-coding RNAs, circular RNAs, exosome, etc. molecular markers in early diagnosis of gastric cancer had better prospects of clinilal application.ConclusionWith the continuous development of molecular biology technology, the values of microRNAs, long non-coding RNAs, circular RNAs, DNA, etc. in early diagnosis of gastric cancer would be further explored.
ObjectiveTo summarize the relationship between exosomes and the occurrence and development of gastrointestinal cancer.MethodsThrough online database, we collected the literatures about the relationship between exosomes and the development of gastrointestinal cancer at home and abroad, and then made an review.ResultsExosomes secreted by gastrointestinal cancer cells were related to tumorigenesis, tumor cell survival, chemoresistance, and early metastasis. Exosomes could play the role of information transmission, and regulation of cell physiology and pathological process in the development of gastrointestinal cancer through a variety of intercellular binding ways, and affectted the occurrence and development of gastrointestinal cancer via epigenetic regulation and tumor related signal transduction mechanism. They had been proved to be biomarkers, targets, and drug carriers for the treatment of gastrointestinalcancer.ConclusionIt is a new way to explore the molecular mechanism of exosomes in the development of gastrointestinal cancer.
ObjectiveTo evaluate the changes in the expression and significance of serum exosomal miRNAs in patients with DeBakey typeⅠacute aortic dissection (AAD). MethodsTwelve male patients with AAD and six healthy male medical examiners from our hospital were retrospectively included in this study. According to the time of chest pain, the AAD patients were divided into an AAD group within 24 h of chest pain onset, aged 47.00±8.79 years and an AAD group within 48 h of chest pain onset, aged 50.17±9.99 years. The healthy males were allocated to a control group, aged 49.17±4.26 years. Serum exosomal miRNAs were isolated, identified and quantified, and then differentially expressed exosomal miRNAs were screened. The bioinformatic analyses such as GO and KEGG were performed on the differentially expressed exosomal miRNAs. ResultsHigh-throughput screening results revealed differential expression of AAD serum exosomal miRNAs. The upregulated miRNAs of AAD groups was hsa-miR-574-5p (P<0.05), and downregulated miRNAs were hsa-miR-223-3p, hsa-miR-146b-5p, hsa-miR-15b-5p, and hsa-miR-155-5p (P<0.05). Further bioinformatic analysis of the above miRNAs revealed that they were mainly enriched in signaling pathways such as transforming growth factor-β, cell cycle and endoplasmic reticulum protein synthesis. ConclusionDifferential expressions of serum exosomal miRNAs in AAD patients may be related to the pathogenesis of AAD, providing new ideas and clues for further exploration of AAD diagnostic markers and pathogenesis.
Objective To summarize the bioactive substances contained in bacterial extracellular vesicles (EVs) and their mechanisms in mediating bacterial-bacterial and bacterial-host interactions, as well as their mechanisms for use in implant infection-associated clinical guidance. Methods A wide range of publications on bacterial-derived EVs were extensively reviewed, analyzed, and summarized. Results Both gram-negative bacteria (G– bacteria) and gram-positive bacteria (G+ bacteria) can secrete EVs which contain a variety of bioactive substances, including proteins, lipids, nucleic acids, and virulence factors, and mediate bacterial-bacterial and bacterial-host interactions. EVs play an important role in the pathogenic mechanism of bacteria. Conclusion Bioactive substances contained within bacteria-derived EVs play an important role in the pathogenesis of bacterial infectious diseases. In-depth study and understanding of their pathogenic mechanisms can provide new insights which will improve early clinical diagnosis, prevention, and treatment of implant-associated infection. However, at present, research in this area is still in its infancy, and many more in-depth mechanisms need to be further studied.
ObjectiveTo investigate the effect of microRNA-135a (miR-135a) in human amnion mesenchymal stem cell exosome (hAMSC-Exo) on the migration of fibroblasts.MethodsThe hAMSC-Exo was extracted with exosomes separation kit and identified, the effect of hAMSC-Exo on fibroblasts migration was detected by scratch test. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the relative expression of miR-135a gene in hAMSC-Exo after overexpression of miR-135a. Scratch test was used to detect the effect of hAMSC-Exo on the migration of fibroblasts after overexpression and knockdown of miR-135a. Western blot was used to detect the migration related proteins of fibroblasts [large tumor suppressor 2 (LATS2), E-cadherin, N-cadherin, and α smooth muscle actin (α-SMA)] after overexpression and knockdown of miR-135a. The 293T cell exosomes and hAMSC-Exo were used as control.ResultshAMSC-Exos were extracted successfully. Scratch test results showed that hAMSC group had the strongest ability to promote fibroblasts migration, and GW4869 (exosome inhibitor) treatment group had reduced ability to promote fibroblasts migration. qRT-PCR test showed that the relative expression of miR-135a gene in hAMSC-Exo increased significantly after over expression of miR-135a. Scratch test results showed that after over expression of miR-135a, hAMSC-Exo enhanced the migration ability of fibroblasts, while after knockdown of miR-135a, hAMSC-Exo weakened the migration ability of fibroblasts. Western blot results showed that the expressions of E-cadherin, N-cadherin, LATS2 were down regulated and α-SMA was up regulated in each hAMSC-Exo treatment group when compared with 293T cell exosomes group; after over expression of miR-135a, hAMSC-Exo decreased the expressions of E-cadherin, N-cadherin, LATS2 and increased the expression of α-SMA; while after knockdown of miR-135a, the ability of hAMSC-Exo was weakened.ConclusionmiR-135a in hAMSC-Exo can promote fibroblasts’ migration, inhibit the expressions of E-cadherin, N-cadherin, LATS2, and promote the expression of α-SMA.
ObjectiveTo explore the potential therapeutic effects of endothelial progenitor cells derived small extracellular vesicles (EPCs-sEVs) on spinal cord injury in mice.MethodsEPCs were separated from femur and tibia bone marrow of 20 C57BL/6 male mice, and identified by double fluorescence staining and flow cytometry. Then the EPCs were passaged and the cell supernatants from P2-P4 generations EPCs were collected; the EPCs-sEVs were extracted by ultracentrifugation and identified by transmission electron microscopy, nanoflow cytometry, and Western blot. Forty C57BL/6 female mice were randomly divided into 4 groups (n=10). The mice were only removed T10 lamina in sham group, and prepared T10 spinal cord injury models in the model group and the low and high concentration intervention groups. After 30 minutes, 3 days, and 7 days of operation, the mice in low and high concentration intervention groups were injected with EPCs-sEVs at concentrations of 1×109 and 1×1010cells/mL through the tail vein, respectively. The behavioral examinations [Basso Mouse Scale (BMS) score, inclined plate test, Von Frey test] , and the gross, HE staining, and immunohistochemical staining were performed to observe the structural changes of the spinal cord at 4 weeks after operation. Another 3 C57BL/6 female mice were taken to prepare T10 spinal cord injury models, and DiR-labeled EPCs- sEVs were injected through the tail vein. After 30 minutes, in vivo imaging was used to observe whether the EPCs-sEVs reached the spinal cord injury site.ResultsAfter identification, EPCs and EPCs-sEVs derived from mouse bone marrow were successfully obtained. In vivo imaging of the spinal cord showed that EPCs-sEVs were recruited to the spinal cord injury site within 30 minutes after injection. There was no significant difference in BMS scores and the maximum angle of the inclined plate test between two intervention groups and the model group within 2 weeks after operation (P>0.05), while both were significantly better than the model group (P<0.05) after 2 weeks. The Von Frey test showed that the mechanical pain threshold of the two intervention groups were significantly higher than that of model group and lower than that of sham group (P<0.05); there was no significant difference between two intervention groups (P>0.05). Compared with the model group, the injured segment of the two intervention groups had smaller spinal cord tissue defects, less mononuclear cells infiltration, more obvious tissue structure recovery, and more angiogenesis, and these differences were significant (P<0.05); there was no significant difference between the two intervention groups.ConclusionEPCs-sEVs can promote the repair of spinal cord injury in mice and provide a new plan for the biological treatment of spinal cord injury.
Objective To investigate the effects of the MKN-45 gastric cancer cell exosomes carrying microRNA-552 (miR-552) on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVEC). Methods ① The MKN-45 cells were divided into MKN-45 blank control group (no transfection), MKN-45 miR-552 inhibitor group [transfection of plasmid inhibiting mir-552 expression (mir-552 inhibitor plasmid)], and MKN-45 negative control group [transfection of negative control plasmid (empty plasmid)], the exosomes were extracted, purified, and identified. Western blotting was used to detect the protein expression of exosomal markers [CD63, CD9, and tumor susceptibility gene 101 (TSG101)]. ② The HUVEC cells were divided into HUVEC control group (added PBS), HUVEC-exosome group (co-cultured with exosomes of MKN-45 cell), HUVEC-negative control exosome group (co-cultured with exosomes of MKN-45 cell transfected with negative control plasmid), and HUVEC-miR-552 inhibitor exosome group (co-cultured with exosomes of MKN-45 cell transfected with miR-552 inhibitor plasmid), exosomes tracing experiment was used to detect whether exosomes entered HUVEC cells. Real-time fluorescent quantitative PCR method was used to detect the expression of miR-552, the MTT method was used to detect the proliferation of HUVEC cells, the Transwell chamber method was used to detect the migration of HUVEC cells, the angiogenesis test was used to detect the angiogenesis ability. Results This study successfully extracted exosomes from MKN-45 gastric cancer cells. Observed by transmission electron microscope, the exosomes were all round or elliptical, with a diameter of 100–150 nm, and the exosomal vesicle structure could be seen. Western blotting detection showed that the surface markers of exosomes (CD63, CD9, and TSG101 protein) were expressed in exosomes. The results of the tracing experiment showed that exosomes derived from MKN-45 cells were successfully internalized by HUVEC cells. After MKN-45 cells were transfected with miR-552 inhibitor plasmid, compared with the MKN-45 blank control group and MKN-45 negative control group, the relative expression level of miR-552 in the exosomes decreased (P<0.05). Compared with the HUVEC control group, the cell proliferation rate at 24, 48 and 74 h increased, as well as number of migration, tubule formation nodes, and relative expression level of miR-552 in the HUVEC-exosomes group increased (P<0.05). Compared with the HUVEC-negative control exosome group, the cell proliferation rate at 24, 48 and 74 h decreased, as well as the number of migration, tubule formation nodes, and relative expression level of miR-552 in the HUVEC-miR-552 inhibitor exosome group decreased (P<0.05). Conclusion The exosomes of gastric cancer cells carrying miR-552 can significantly promote the proliferation, migration, and angiogenesis of HUVEC cells.
ObjectiveTo investigate the expression level of exosome microRNA-21 (miRNA-21) in the bile and its clinical diagnostic value for the patients with cholangiocarcinoma. MethodsIn this study, 45 cases of cholangiocarcinoma admitted to Dongfeng General Hospital from August 2019 to December 2021 and met the inclusion criteria were selected and 35 patients with benign diseases of bile duct (choledocholithiasis or benign stricture of bile duct) during the same period were selected as control. The exosome in the bile was extracted by hypervelocity centrifugation method and identified. The exosome miRNA was extracted from the bile using a kit, then the expression level of miRNA-21 was detected by real-time fluorescent quantitative PCR. The diagnostic value of exosome miRNA-21 in the bile for cholangiocarcinoma was analyzed by receiver operating characteristic curve (ROC). ResultsThe isolated exosome in the bile conformed to the characteristics of recognized exosome and the concentration was higher. The average expression level of exosome miRNA-21 in the bile of the patients with cholangiocarcinoma was statistically higher than that in the patients with benign diseases of bile duct (59.45 verses 25.41, t=3.445, P<0.001). The area under the ROC curve was 0.715 [95%CI (0.602, 0.827), P=0.001]. The sensitivity and specificity of miRNA-21 in the diagnosis of cholangiocarcinoma were 75.6% and 62.9%, respectively. ConclusionFrom the results of this study, exosome miRNA-21 expression in bile is higher and it may be a potential early diagnostic marker for patients with cholangiocarcinoma.
ObjectiveTo summarize the research progress of mesenchymal stem cells derived exosomes (MSCs-EXOs) in wound repair in recent years.MethodsThe literature about the role of MSCs-EXOs in wound repair at home and abroad was extensively consulted. The mechanism of MSCs-EXOs in wound repair and its clinical application prospects were summarized and analyzed.ResultsMSCs-EXOs can inhibit early inflammatory reaction, promote angiogenesis, proliferation, and migration of epithelial cells, regulate collagen synthesis, and inhibit scar proliferation in the later stage of wound healing. Compared with MSCs, MSCs-EXOs have many advantages, such as high stability, easy storage, non-tumorigenicity, no proliferation, easy quantitative use, and so on. It has broad clinical application prospects.ConclusionMSCs-EXOs can promote wound repair and hopefully develop into a clinical product to promote the repair of acute or chronic wounds.