尿外泌体在膀胱尿路上皮细胞癌中的表达及临床意义

目的:探讨尿外泌体(exosome)在膀胱尿路上皮细胞癌中的表达情况及其临床意义。方法:采用超速离心法提取30例膀胱尿路上皮细胞癌患者和15例健康人群的尿外泌体。利用投射电镜观察形态,BCA法进行蛋白定量,Western blot检测尿外泌体表面分子CD9。结果:健康人群尿外泌体水平[(125.99±47.71)μg/μL]与膀胱尿路上皮细胞癌患者尿外泌体表达水平[(259.74±57.47)μg/μL]差异有统计学意义。根据肿瘤的浸润程度,非肌层浸润性膀胱癌患者尿外泌体水平与肌层浸润性膀胱癌患者尿外泌体水平差异有统计学意义。而肌层浸润性膀胱癌各期患者尿外泌体水平差异无统计学意义。结论:尿外泌体检测可能为膀胱癌的早期诊断提供一种可行的方案。     

外泌体lncRNA在肿瘤中的研究进展

外泌体是肿瘤液态活检的明星分子,作为"胞间通讯"的信使可以在全身体液循环.随着科学家们对长链非编码RNA(lncRNA)的深入研究,发现lncRNA在表观遗传修饰、转录调控与转录后调控等多个层面发挥作用.在肿瘤发生、发展过程中,外泌体携带的lncRNA能够改变肿瘤微环境,介导肿瘤细胞增殖、转移和耐药,促进血管生成和介导...     

外泌体在肿瘤体外诊断中的临床研究和应用前景

外泌体由于富含生物信息分子,提供了潜在的生物标志物,在肿瘤体外诊断中显示出良好的临床应用前景。阐述了外泌体的功能、在体外诊断中的优势及检测方法,并深入探讨了外泌体在肺癌、肠癌、卵巢癌、胃癌、胰腺癌、膀胱癌、骨与软组织肉瘤等肿瘤体外诊断中的价值和临床获批情况,展望了外泌体在体外诊断领域的发展趋势。     

Exosomes play roles in sequential processes of tumor metastasis

Overwhelming evidence demonstrates that exosomes, a series of biologically functional small vesicles of endocytic origin carrying a variety of active constituents, especially tumor-derived exosomes, contribute to tumor progression and metastasis. This review focuses on the specific multifaceted roles of exosomes in affecting sequenced four crucial processes of metastasis, through which cancer cells spread from primary to secondary organs and finally form macroscopic metastatic lesions. First, exosomes modulate the primary tumor sites to assist cancer growth and dissemination. In this part, five main biological events are reviewed, including the transfer of oncogenic constituents, the recruitment and activation of fibroblasts, the induction of angiogenesis, immunosuppression and epithelial-mesenchymal transition (EMT) promotion. In Step 2, we list two recently disclosed mechanisms during the organ-specific homing process: the exosomal integrin model and exosomal epidermal growth factor receptor (EGFR)/miR-26/hepatocyte growth factor (HGF) model. Subsequently, Step 3 focuses on the interactions between exosomes and pre-metastatic niche, in which we highlight the specific functions of exosomes in angiogenesis, lymphangiogenesis, immune modulation and metabolic, epigenetic and stromal reprogramming of pre-metastatic niche. Finally, we summarize the mechanisms of exosomes in helping the metastatic circulating tumor cells escape from immunologic surveillance, survive in the blood circulation and proliferate in host organs.     

Melatonin-stimulated exosomes enhance the regenerative potential of chronic kidney disease-derived mesenchymal stem/stromal cells via cellular prion proteins

Chronic kidney disease (CKD) is caused by dysfunctional kidneys, which result in complications like cardiovascular diseases. Chronic kidney disease-induced pathophysiological conditions decrease efficacy of autologous mesenchymal stem/stromal cell (MSC)-based therapy by reducing MSC functionality. To enhance therapeutic potential in patients with CKD, we isolated exosomes derived from melatonin-treated healthy MSCs (MT exosomes) and assessed the biological functions of MT exosome–treated MSCs isolated from patients with CKD (CKD-MSCs). Treatment with melatonin increased the expression of cellular prion protein (PrP^C) in exosomes isolated from MSCs through the upregulation of miR-4516. Treatment with MT exosomes protected mitochondrial function, cellular senescence, and proliferative potential of CKD-MSCs. MT exosomes significantly increased the level of angiogenesis-associated proteins in CKD-MSCs. In a murine hindlimb ischemia model with CKD, MT exosome–treated CKD-MSCs improved functional recovery and vessel repair. These findings elucidate the regenerative potential of MT exosome–treated CKD-MSCs via the miR-4516-PrP^C signaling axis. This study suggests that the treatment of CKD-MSCs with MT exosomes might be a powerful strategy for developing autologous MSC-based therapeutics for patients with CKD. Furthermore, miR-4516 and PrP^C could be key molecules for enhancing the regenerative potential of MSCs in ischemic diseases.     

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??Exosomes refer to 40??100 nm extracellular vesicles secreted from various types of cells that contain cell's lipid??proteins and nucleic acids??which can be accessed to recipient cell by plasma membrane fusion??surface receptor-mediated uptake??and cell internalization??affecting the function and activity of the recipient cell. The RNA and miRNA contained in exosomes can be transferred with the exosomes to the recipient cells??and are translated in the recipient cells??which is a new carrier of genetic exchange. The research of exosomes in oral field focuses on exosome-mediated cell communication and modulating immunocompetence. In this paper??the exosomes derived from salivary origin??oral cancer sources and periodontal pathogens were reviewed to summarize the research progress in exosomes of the oral area.     

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??Objective    To study the influence of exosome secreted by the human bone marrow mesenchymal stem cells ??hBMMSCs?? on proliferation and differentiation of periodontal ligament stem cells ??hPDLSCs????and to provide experimental basis and evidence of the mechanism of hBMMSCs in promoting periodontal tissue regeneration. Methods    hPDLSCs were cultured by enzyme digestion method and hBMMSCs were cultured by centrifugation method?? and the immunophenotype was identified by flow cytometry. Supernatant of hBMMSCs in P3 was collected?? exosome was extracted by kit and observed by SEM??and CD63 level was tested by WB. The experiment group was treated by exosome of hBMMSCs and control group was treated by DD water. hPDLSCs proliferation was tested by MTT and colony unite forming was tested in 7 days. After osteogenetic induction?? ALP and Alizarin Red staining were performed and quantitative analysis was carried. Meanwhile osteogenesis-related gene expression was tested by qPCR. Results    hPDLSCs positively expressed CD29?? CD44?? CD90?? CD146 and Stro-1?? hBMMSCs positively expressed CD29?? CD44?? CD90 and CD106??both negatively expressed CD14?? CD34 and CD45. Exosome secreted by hBMMSCs were small ball-shaped under SEM and expressed CD63 strongly by WB. The proliferation and colony unite forming of experimental group was significantly higher than control group ??P < 0.05??. The quantitative expression of ALP and alizarin red staining after osteogenetic induction were significantly stronger than the control group ??P < 0.05??. The osteogenetic gene expression??including Runx2?? OCN?? ALP?? BSP and Col - ?? was significantly higher than that of control group by qPCR ??P < 0.05??. Conclusion    The exosome secreted by hBMMSCs can promote??proliferation and osteogenesis of hPDLSCs in vitro.     

Metabolomic Identification of Exosome-Derived Biomarkers for Schizophrenia: A Large Multicenter Study

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.