Long-term ketamine abuse reduces expression of BDNF, while inducing phosphorylation of ERK1/2 in the bladder wall. This may play an important role in the pathogenesis of ketamine-associated LUTS.

In order to identify the anti-invasive and anti-metastatic effect of the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) on the human bladder cancer EJ cell line, and to study its impact on the expression of wingless-type mouse mammary tumor virus integration site family, member 5a (Wnt5a), the phosphorylation of c-Jun N-terminal kinase (JNK), the expression levels of matrix metalloproteinase-2 (MMP-2), and the migration and invasion of EJ cells, migration and Matrigel invasion assays, as well as western blot analyses, were used in the present study. The results of the migration and Matrigel invasion assays indicated that the inhibitor of JNK SP600125 could inhibit the effect of 4-HPR on EJ cells. The expression of Wnt5a and MMP-2, and the phosphorylation of JNK, were analyzed by western blotting. The data revealed that 4-HPR inhibited the migration and invasion of bladder cancer cells through stimulating Wnt5a activation, causing the downregulation of MMP-2 expression and enhancing the phosphorylation of JNK in these cells. However, JNK signaling did not appear to have a direct effect on the expression of MMP-2. The present study demonstrated that 4-HPR may be a potent anti-invasive and anti-metastatic agent that functions via the Wnt5a/JNK and Wnt5a/MMP-2 signaling pathways.

Purpose This study aims to carry out a pan-cancer analysis of kinesin family member 23 (KIF23) and construct a predictive model for the prognosis of clear cell renal cell carcinoma (ccRCC) patients. Methods We evaluated the differential expression of KIF23 in pan-cancer by The Cancer Genome Atlas (TCGA) and Oncomine database. Then, the correlation between KIF23 with prognosis, clinical grade, stage, immune subtype, tumor mutation burden (TMB), microsatellite instability (MSI) and immune microenvironment was explored by TCGA, an integrated repository portal for tumor-immune system interactions (TISIDB) and cBioPortal. Subsequently, we screened out ferroptosis-related genes (FRGs) related to KIF23 and constructed a risk score model. Univariate Cox analysis was used to determine independent prognostic factors for ccRCC overall survival (OS), and a nomogram was established. Furthermore, gene set enrichment analysis (GSEA) was applied to study the biological functions and pathways of KIF23. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to evaluate the expression of KIF23. Results KIF23 was highly expressed in most tumors. Further, KIF23 was strongly correlated with prognosis, clinical grade, stage, immune subtype, TMB, MSI and immune microenvironment in different tumors. We found that KIF23 was significantly associated with all aspects of ccRCC. Then, 8 FRGs were identified to construct a risk score model together with KIF23. And a prognostic nomogram prediction model of OS was established. After GSEA analysis, cell cycle, condensed chromosome and other physiological processes were screened out. Finally, qRT-PCR verified the high expression of KIF23 in ccRCC cell lines than normal kidney cell line. Conclusion KIF23 may act as a pivotal part in occurrence and progression of different tumors. In ccRCC, KIF23 can be a great prognostic biomarker, and the nomogram based on KIF23 may contribute to better treatment plans for ccRCC patients.

Despite extensive research, urosepsis remains a life-threatening, high-mortality disease. Currently, animal models of urosepsis widely accepted by investigators are very scarce. This study aimed to establish a standardized and reproducible model of urosepsis in rats. Forty adult Wistar rats were randomly divided into four groups according to the concentration of injected E. coli suspensions: Sham, Sep 3×, Sep 6×, and Sep 12×. Because the ureter is so thin and fragile, no conventional needle can be inserted into the ureter, which is probably why rats are rarely used to develop models of urosepsis. To solve this problem, the left ureter was ligated in the first procedure. After 24 hours, the left ureter above the ligation was significantly dilated, then saline or different concentrations of E. coli at 3 ml/kg were injected into the left renal pelvis using a 30G needle. The left ureter was subsequently ligated again at a distance of 1 cm from the renal hilum to maintain high pressure in the renal pelvis. Following injection of E. coli or saline for 24 h, three rats from each group were sacrificed and their organs (lung, liver, and right kidney) were collected. In contrast, the remaining seven rats continued to be observed for survival. At 10 days after E. coli injection, rats in the sep12× group had a higher mortality rate (100%) compared to the sep3× group (28.6%) or the sep6× group (71.4%). The significant changes in peripheral blood WBC count, serum IL-6 and TNF-α levels were also in the sep12× group. In addition, rats in the sepsis group showed multi-organ dysfunction, including damage to the lungs, liver, and kidneys. The establishment of a standardized rat model of urosepsis may be of great value for studying the pathophysiological of urosepsis.

Ubiquitin C-terminal hydrolase L5 (UCHL5) is a deubiquitinating enzyme (DUB) that removes ubiquitin from its substrates. Associations between UCHL5 and cancer have been reported in various tissues, but the effect of UCHL5 on bladder cancer has not been thoroughly investigated. This study investigates the expression and function of UCHL5 in bladder cancer. UCHL5 was shown to be abnormally expressed using IHC of tissue microarray and Western blotting. Several procedures were performed to assess the effect of UCHL5 overexpression or knockdown on bladder cancer, such as cell proliferation, colony formation, wound-healing, and Transwell assays. In addition, RNA-Seq and Western blotting experiments were used to verify the status of downstream signaling pathways. Finally, bladder cancers with knockdown or overexpression of UCHL5 were treated with either SC79 or LY294002 to examine the participation of the AKT/mTOR signaling pathway and the expression of downstream targets c-Myc, SLC25A19, and ICAM5. In contrast to adjacent tissue samples, we discovered that UCHL5 was substantially expressed in bladder cancer samples. We also found that UCHL5 downregulation significantly suppressed both tumor growth in vivo and cell proliferation and migration in vitro. According to RNA-Seq analyses and Western blotting experiments, the expression of c-Myc, SLC25A19, and ICAM5 was modified as a result of UCHL5 activating AKT/mTOR signaling in bladder cancer cells. All things considered, our findings show that increased UCHL5 expression stimulates AKT/mTOR signaling, subsequently triggering the expression of c-Myc, SLC25A19, and ICAM5, which in turn promotes carcinogenesis in bladder cancer. UCHL5 is therefore a potential target for therapy in bladder cancer patients.