Renal cancer is one of the most extensively studied human tumors today, with clear cell renal cell carcinoma accounting for approximately 80% of all cases. Despite recent advances in research on clear cell renal cell carcinoma, advanced distant metastasis of the disease, delay in diagnosis, as well as drug resistance remain major problems. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, exosomes have attracted widespread attention for their role in tumor development. It has been reported that tumor-derived exosomes may act as regulators and have an important effect on the metastasis, drug resistance formation, and providing targets for early diagnosis of clear cell renal cell carcinoma. Therefore, the extensive study of tumour-derived exosomes will provide a meaningful reference for the development of the diagnostic and therapeutic field of clear cell renal cell carcinoma. This article reviews the biological role and research progress of tumor-derived exosomes in different aspects of premetastatic niche formation, tumor angiogenesis, and epithelial-mesenchymal transition during the progression of clear cell renal cell carcinoma. In addition, the role of tumor-derived exosomes in the development of drug resistance in clear cell renal cell carcinoma is also addressed in this review. Furthermore, recent studies have found that cargoes of exosomes in serum and urine, for example, a series of miRNAs, have the potential to be biological markers of clear cell renal cell carcinoma and provide meaningful targets for early diagnosis and monitoring of tumors, which is also covered in this article.

Introduction Erectile dysfunction (ED) is a common disease among elderly men, and novel therapy methods are needed for drug-refractory ED. As an extracellular vesicle, stem cell–derived exosomes displayed erectile function improvement in rat ED models in some preclinical studies. However, the therapeutic efficacy has not been comprehensively evaluated. Aim To study the therapeutic effects of stem cell–derived exosomes on ED in preclinical studies and to investigate the potential mechanisms responsible for the efficacy. Methods The systematic literature search was conducted in Web of Science, PubMed, and Embase to retrieve studies utilizing stem cell–derived exosomes for ED treatment. We extracted data of intracavernous pressure/mean artery pressure (ICP/MAP), and cavernosum structural changes in rat ED models before and after stem cell-derived exosome therapy. RevMan 5.3 was used to perform meta-analyses of ICP/MAP and cavernosum microstructural changes. Publication bias was assessed with the Egger test and funnel plot by Stata 15.0 (StataCorp). Main Outcome Measures Outcomes included ICP/MAP, smooth muscle, and endothelial markers—such as the ratio of smooth muscle to collagen and the expression of α-SMA (alpha smooth muscle actin), CD31 (cluster of differentiation 31), nNOS and eNOS (neuronal and endothelial nitric oxide synthase), TGF-β1 (transforming growth factor β1), and caspase 3 protein-to evaluate erectile function and microstructural changes. Forest plots of effect sizes were performed. Results Of 146 studies retrieved, 11 studies were eligible. Pooled analysis showed that stem cell–derived exosomes ameliorated damaged ICP/MAP (standardized mean difference, 3.68; 95% CI, 2.64-4.72; P < .001) and structural changes, including the ratio of smooth muscle to collagen and the expression of α-SMA, CD31, nNOS, eNOS, TGF-β1, and caspase 3 protein. Subgroup analysis indicated that exosome type and ED model type made no difference to curative effects. Conclusion This meta-analysis suggests the therapeutic efficacy of stem cell–derived exosomes for ED. Exosomes may restore erectile function by optimizing cavernosum microstructures.

Objectives Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it’s likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined. Methods Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan–Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII. Results A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (<150 mg/dL) or ATIII (<80%) activity was associated with significantly higher in-hospital mortality (fibrinogen HR [95% CIs] 2.01 [1.79, 2.27]; ATIII 3.73 [1.11, 12.54]). The HR [95% CIs] of low fibrinogen remained significant 1.29 (1.13, 1.48) in multivariate analysis. The RCS curve showed nearly linear relationship. Subgroup analysis also proved the robustness of the association between fibrinogen and in-hospital mortality. Kaplan–Meier survival curve and ROC demonstrated the predictive capability of fibrinogen and ATIII. Conclusion Low fibrinogen is an independent predictor of in-hospital mortality in critically ill patients with AKI. Low ATIII activity is also likely to impact the risk of in-hospital death.