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Although fibroblasts are responsible for the production and deposition of extracellular matrix in renal fibrosis, their origin is controversial. Circulating fibroblast precursors may contribute to the pathogenesis of renal fibrosis, but the signaling mechanisms underlying the recruitment of bone marrow-derived fibroblast precursors into the kidney in response to injury are incompletely understood. Here, in the unilateral ureteral obstruction model of renal fibrosis, tubular epithelial cells upregulated the chemokine CXCL16 in obstructed kidneys, and circulating fibroblast precursors expressed the CXCL16 receptor, CXCR6. Compared with wild-type mice, CXCL16-knockout mice accumulated significantly fewer bone marrow-derived fibroblast precursors in obstructed kidneys. CXCL16-knockout mice also exhibited significantly fewer CD45-, collagen I-, and CXCR6-triple-positive fibroblast precursors in injured kidneys. Furthermore, targeted deletion of CXCL16 inhibited myofibroblast activation, reduced collagen deposition, and suppressed expression of collagen I and fibronectin. In conclusion, CXCL16 contributes to the pathogenesis of renal fibrosis by recruiting bone marrow-derived fibroblast precursors.

Compared with conservative treatment, operative treatment can effectively reduce the risk of re-rupture but increase the probability of complications. The increased complication risk may be associated with open repair surgery. However, no sufficient evidence is available from current studies to support the belief that operation may lead to better functional recovery.

Patients with DM had a larger FAZ, and patients with more severely damaged retinas had a much larger FAZ. OCT angiography is a new convenient and noninvasive method for studying the FAZ. This novel examination will yield considerable amounts of data that cannot be obtained using previous research methods.

Key Points Increased quiescence of HSCs and HPCs in leukemogenesis, and reversible suppression of HSCs was observed in leukemic bone marrow. A novel inhibitory role of Egr3 in HSC proliferation was revealed by leukemic infiltration in bone marrow.

ObjectivesTo investigate whether ureteroscopy (URS) before radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an impact on oncological outcomes. Patients and MethodsWe performed a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described URS performed on patients with UTUC and conducted a standard meta-analysis on survival outcomes. ResultsOur meta-analysis included eight eligible studies containing 3975 patients. The results were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95% CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69-1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P = 0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29-1.77; P < 0.001). When excluding previous bladder tumour history, the result for IRFS was a HR of 1.81 (95% CI 1.53-2.13; P < 0.001). ConclusionsThis meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS, or MFS in patients with UTUC. However, patients were at higher risk of intravesical recurrence after RNU when they had undergone URS before RNU. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence.

Background: Accumulating evidence indicates that long non-coding RNAs (lncRNAs) are potential biomarkers and key regulators of tumour development and progression. SOX2 overlapping transcript (SOX2OT) is a novel lncRNA that acts as a potential biomarker and is involved in the development of cancer and cancer stem cells. However, the clinical significance and molecular mechanism of SOX2OT in bladder cancer are still unknown. Methods: The expression level of SOX2OT was determined by RT-qPCR in a total of 106 patients with urothelial bladder cancer and in different bladder cancer cell (BCC) lines. Bladder cancer stem cells (BCSCs) were isolated from BCCs using flow cytometry based on the stem cell markers CD44 and ALDH1. Loss-of-function experiments were performed to investigate the biological roles of SOX2OT in the stemness phenotype of BCSCs. Comprehensive transcriptional analysis, RNA FISH, dual-luciferase reporter assays and western blots were performed to explore the molecular mechanisms underlying the functions of SOX2OT. Results: SOX2OT was highly expressed in bladder cancer, and increased SOX2OT expression was positively correlated with a high histological grade, advanced TNM stage and poor prognosis. Further experiments demonstrated that knockdown of SOX2OT inhibited the stemness phenotype of BCSCs. Moreover, inhibition of SOX2OT delayed xenograft tumour growth and decreased metastases in vivo. Mechanistically, we found that SOX2OT was mainly distributed in the cytoplasm and positively regulated SOX2 expression by sponging miR-200c. Furthermore, SOX2 overexpression reversed the SOX2OT silencing-induced inhibition of the BCSC stemness phenotype. Conclusion: This study is the first to demonstrate that SOX2OT plays an important regulatory role in BCSCs and that SOX2OT may serve as a potential diagnostic biomarker and therapeutic target in bladder cancer.

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