Both PK-TURBT and HoL-TURBT might prove to be preferable alternatives to CM-TURBT management of non-muscle invasive bladder cancer. PK-TURBT and HoL-TURBT, however, did not demonstrate an obvious advantage over CM-TURBT in tumor recurrence rate.

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Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.

The conversion of skeletal muscle fiber from fast twitch to slow‐twitch is important for sustained and tonic contractile events, maintenance of energy homeostasis, and the alleviation of fatigue. Skeletal muscle remodeling is effectively induced by endurance or aerobic exercise, which also generates several tricarboxylic acid ( TCA ) cycle intermediates, including succinate. However, whether succinate regulates muscle fiber‐type transitions remains unclear. Here, we found that dietary succinate supplementation increased endurance exercise ability, myosin heavy chain I expression, aerobic enzyme activity, oxygen consumption, and mitochondrial biogenesis in mouse skeletal muscle. By contrast, succinate decreased lactate dehydrogenase activity, lactate production, and myosin heavy chain II b expression. Further, by using pharmacological or genetic loss‐of‐function models generated by phospholipase Cβ antagonists, SUNCR 1 global knockout, or SUNCR 1 gastrocnemius‐specific knockdown, we found that the effects of succinate on skeletal muscle fiber‐type remodeling are mediated by SUNCR 1 and its downstream calcium/ NFAT signaling pathway. In summary, our results demonstrate succinate induces transition of skeletal muscle fiber via SUNCR 1 signaling pathway. These findings suggest the potential beneficial use of succinate‐based compounds in both athletic and sedentary populations.

Objectives: MiR-21 induces neoplastic transformation, cell proliferation, and metastasis and downregulates programmed cell death4 (PDCD4) in some cancers. The aim of this study was to investigate the roles and interactions of PDCD4 and miR-21 in human renal cell carcinoma (RCC). Materials and Methods: A total of 32 paired tumor and normal tissue specimens from RCC patients as well as three renal cancer cell lines (786-O, A498, caki-1) and one normal epithelial kidney cell line (HK-2) were studied. The expression levels of PDCD4 (protein and mRNA) and miR-21 were examined by Western blot analysis and by qRT-PCR and luciferase reporter assays. Furthermore, we transfected 786-O cells with pre-miR-21 (mimics) and anti-miR-21 (inhibitor) and then again analyzed the expression of PDCD4 protein and mRNA, and determined cell proliferation and transformation capabilities by EDU and soft agar colony formation assay. Results: MiR-21 expression was significantly upregulated in RCC, metastatic RCC specimens and renal cancer cell lines (A498, 786-O, caki-1) compared to normal non-metastatic RCC specimens and HK-2 cells (P<0.05). In contrast, PDCD4 protein expression significantly decreased (P<0.05), whereas PDCD4 mRNA expression remained unaltered (P>0.05). Moreover, we observed a significant reduction in PDCD4 protein levels in miR-21mimic-transfected cells, but a significant increase in miR-21inhibitor-transfected cells (P<0.05), whereas PDCD4 mRNA was practically unaltered (P>0.05). Furthermore, miR-21mimic-transfected cells exhibited increased cell proliferation and transformation capacity according to EDU analysis and soft agar formation assay, whereas miR-21inhibitor-transfected cells exhibited the opposite phenomenon(P<0.05). Conclusions: MiR-21 not only promoted cancer cell hyperplasia and contributed to tumor cell transformation and metastasis, but also post-transcriptionally downregulated PDCD4 protein expression. PDCD4 and miR-21 expression levels potentially play an important role in renal cell cancer.