Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI); however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated. Tubular cell proliferation and apoptosis were identified by Ki67 or terminal-deoxynucleotidyl transferase-mediated nick end labeling immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin staining were used for assessing renal fibrosis. The mRNA or protein expression in the kidney was measured by quantitative reverse transcription-PCR or Western blot, respectively. The total collagen concentration was also determined. In vitro, NRK-52E cells that treated with MVs under hypoxia injury and with HGF or U0126 administration were used, and cell cycle analysis was performed. The effects of hWJMSC-MVs on enhancing the proliferation and mitigating the apoptosis of renal cells, abrogating IRI-induced fibrosis, improving renal function, decreasing collagen deposition, and altering the expression levels of epithelial–mesenchymal transition and cell cycle-related proteins in IRI rats were found. In vitro experiment showed that hWJMSC-MVs could induce G2/M cell cycle arrest and decrease the expression of collagen deposition-related proteins in NRK-52E cells after 24 or 48 h. However, U0126 treatment reversed these effects. In conclusion, MVs derived from hWJMSCs ameliorate IR-induced renal fibrosis by inducing G2/M cell cycle arrest via Erk1/2 signaling.

Objective: To compare the efficacy and safety of a novel thermochemotherapy scheme and the instillation of pirarubicin (THP) without hyperthermia in patients with intermediate- and high-risk nonmuscle-invasive bladder cancer (NMIBC). Materials and methods: Between June 2012 and December 2016, 300 patients with urothelial carcinoma of the bladder undergoing intravesical adjuvant therapy with THP after transurethral resection of bladder tumors (TURBT) were enrolled in the study. These patients were divided into the CTHC group (thermochemotherapy composed of three consecutive sessions in which only the second hyperthermia was combined with THP, followed by intravesical instillation with THP without using hyperthermia) and the THP group (instillation of THP without hyperthermia). Cystoscopy and urinary cytology were repeated every 3 months. The primary endpoint was 24-month recurrence-free survival (RFS). Secondary endpoints included 24-month progression-free survival (PFS) and adverse event (AE) rates. Results: Baseline characteristics of the CTHC (n = 76) and THP (n = 85) groups were well-balanced. The 24-month RFS was 82.9% in the CTHC group and 63.5% in the THP group (log-rank p = .008). A significantly higher percentage of patients in the CTHC group achieved PFS than in the THP group (97.4% versus 87.1%; log-rank p = .011). There was no significant difference in AEs between the two groups (p > .05). Based on Cox proportional hazards models, CTHC was the only factor that contributed independently to improved RFS (hazard ratio, 0.422; 95% confidence interval, 0.214–0.835; p = .013). Conclusion: The CTHC scheme is a safe and effective adjuvant treatment option after TURBT for patients with intermediate- and high-risk NMIBC.