Search

Background: Bladder cancer (BLCA) is the most prevalent malignant neoplasm of the urinary tract, and ranks seventh as the most frequent systemic neoplasm in males. Dysregulation of programmed cell death (PCD) has been implicated in various stages of cancer progression, including tumorigenesis, invasion, and metastasis. However, the correlation between multiple PCD modes and BLCA is lacking. Thus, a risk prediction model was built based on 12 models of PCD to predict prognosis and immunotherapy response in patients with BLCA. Methods: The RNA sequencing transcriptome data of BLCA were collected from the Cancer Genome Atlas Program (TCGA) and GEO datasets. Univariate Cox and LASSO regression analyzes were performed to identify PCD‐related genes (PCDRGs) significant for prognosis. Multivariate Cox regression analysis was used to develop a prognostic model for PCD. Survival analysis and chi‐squared test were employed to analyze the survival variations between different risk groups. Univariate and multivariate Cox analyses were performed to evaluate the model as an independent prognostic predictor. A nomogram was formulated using both clinical data and the model to predict the survival rates of BLCA patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed to analyze and elucidate the molecular mechanisms and pathways operating within different risk score groups. Furthermore, the immune landscape was investigated and the efficacy of various anti‐tumor drugs was evaluated for BLCA. Finally, consensus clustering analysis was adopted to explore the association between different PCD clusters and clinical characteristics. Results: Assessment of the public datasets and multivariate Cox analysis yielded 1254 PCDRGs, of which 10 PCDRGs for BLCA were identified. Based on the PCDRGs, a prognostic model was built for BLCA patient prognosis. Compared with the low‐risk group, the high‐risk group had a poorer prognosis. The model predicted area under the curve (AUC) values of 0.751, 0.753, and 0.763, respectively, for 1‐, 3‐, and 5‐year survival of BLCA patients. The nomogram further demonstrated the credibility of the prognosis model. The low‐risk group patients exhibited lower TIDE scores and higher TMB scores, implying better response of the low‐risk group to immunotherapy. The consensus clustering analysis indicated that compared with PCD cluster A, PCD cluster B was significantly more expressed in PCDRGs, suggesting a closer relation of PCD cluster B to PCDRGs. Patients in PCD cluster B had lower risk scores. Conclusion: To summarize, the effects of 12 PCD patterns on BLCA were synthesized and the correlation between PCD and BLCA was explored. These findings provide new and convincing evidence for individualized treatment of BLCA, and help guide the treatment strategy and improve the prognosis of BLCA patients. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate the role and possible mechanism of lncRNA XIST in renal fibrosis and to provide potential endogenous targets for renal fibrosis in obstructive nephropathy (ON)., Methods: The study included 50 cases of ON with renal fibrosis (samples taken from patients undergoing nephrectomy due to ON) and 50 cases of normal renal tissue (samples taken from patients undergoing total or partial nephrectomy due to accidental injury, congenital malformations, and benign tumors). Treatment of human proximal renal tubular epithelium (HK-2) cells with TGF-β1 simulated renal fibrosis in vitro. Cell viability and proliferation were measured by CCK-8 and EdU, and cell migration was measured by transwell. XIST, miR-124-3p, ITGB1, and epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, α-SMA, and fibronectin) were detected by PCR and immunoblot. The targeting relationship between miR-124-3p and XIST or ITGB1 was verified by starBase and dual luciferase reporter gene experiments. In addition, The left ureter was ligated in mice as a model of unilateral ureteral obstruction (UUO), and the renal histopathology was observed by HE staining and Masson staining., Results: ON patients with renal fibrosis had elevated XIST and ITGB1 levels and reduced miR-124-3p levels. The administration of TGF-β1 exhibited a dose-dependent promotion of HK-2 cell viability, proliferation, migration, and EMT. Conversely, depleting XIST or enhancing miR-124-3p hindered HK-2 cell viability, proliferation, migration, and EMT in TGF-β1-damaged HK-2 cells HK-2 cells. XIST functioned as a miR-124-3p sponge. Additionally, miR-124-3p negatively regulated ITGB1 expression. Elevating ITGB1 weakened the impact of XIST depletion on TGF-β1-damaged HK-2 cells. Down-regulating XIST improved renal fibrosis in UUO mice., Conclusion: XIST promotes renal fibrosis in ON by elevating miR-124-3p and reducing ITGB1 expressions., Competing Interests: Declaration of Competing Interest: none, (Copyright © 2024. Published by Elsevier Inc.)

Background: Having a spicy diet and smoking habit may be important factors causing erectile dysfunction (ED). The aim of this study is to investigate the impact of spicy diet and smoking habits on the risk of ED in men, with a focus on the interaction between these lifestyle factors., Methods: Our investigation was conducted as a retrospective analysis spanning from June 2017 to June 2023. Participants underwent interviews utilizing the Structured Interview on Erectile Dysfunction (SIEDY) to evaluate the degree of pathological factors. The International Index of Erectile Function-5 (IIEF-5) was employed as a metric for assessing ED. Additionally, the subjects were comprehensively questioned about their smoking history and dietary preferences, which included an inquiry into how often they consumed spicy meals., Results: Our research involved 373 participants, with 67.6% being individuals with ED. Among the participants, 50.7% were non-smokers and 49.3% were smokers, totaling 188 and 185, respectively. There was no significant difference in the spicy food frequency consumption among smokers with ED. However, non-smokers who consumed spicy food more frequently experienced more severe ED (P=0.02). ED patients showed significant differences in body mass index (BMI), blood glucose and testosterone, which were linked to vascular damage (P=0.03, P=0.02, P=0.04, respectively). Additionally, non-smokers who consumed more spicy food had higher scores on the SIEDY 2 scale, indicating marital factors (P=0.004). In non-smoking participant, a high spicy ratio indicated an even higher risk of ED [odds ratio 2.58, 95% confidence interval: 1.27-5.26; P=0.008], while there was no significant impact on ED in smoking participants (data not shown)., Conclusions: This retrospective study suggests that a considerable consumption of spicy foods is independently correlated with an elevated risk of ED, particularly among non-smoking men., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-26/coif). The authors have no conflicts of interest to declare., (2024 Translational Andrology and Urology. All rights reserved.)

The standard procedure for the micronucleus test in cell lines requires a short exposure (≤0.5 cell cycle) to the test compounds followed by a long recovery (≥1.5 cell cycle), and in case of negative or equivocal results, a second test with extended exposure (≥2 cell cycles) without or with a recovery time. In general the two procedures are advantageous for detecting clastogens and aneugens, respectively. However, whether the recommended procedures apply to micronucleus tests with promutagens in cell lines genetically engineered for expressing biotransformation enzymes has not been identified. In this study, several promutagens dependent on cytochrome P450 (CYP) 2E1 and/or sulfotransferase (SULT) 1A1 were used in the micronucleus test in a Chinese hamster V79-derived cell line expressing human CYP2E1 and SULT1A1 (V79-hCYP2E1-hSULT1A1), with varying exposure/recovery schedules: 3h/21h, 6h/18h, 12h/12h, 18h/6h, and 24h/0h, in comparison with known clastogens and aneugens in V79 control cells. The results showed peaked micronuclei induction by mitomycin C and bleomycin (clastogens) at the 12h/12h schedule, while colchicine and vinblastine (aneugens) showed the strongest effect at 24h/0h. Catechol and trihydroxybenzene (activated by CYP2E1) induced micronuclei most strongly at 6h/18h, whereas somewhat longer exposures were optimal for hydroquinone, another compound activated by CYP2E1. 1-Hydroxymethylpyrene (activated by SULT1A1) and 1-methylpyrene (activated sequentially by CYP2E1 and SULT1A1) produced the highest response with the 18h/6h treatment regimen. Moreover, mitotic arrest by 1-hydroxymethylpyrene was observed in V79-hCYP2E1-hSULT1A1 cells but not in V79 cells, and 1-methylpyrene arrested mitosis in V79-hCYP2E1-hSULT1A1 more strongly than in V79 cells. Our study suggests that intracellular bioactivation of promutagens may not delay the induction of micronuclei in the present model, and 1-methylpyrene and 1-hydroxymethylpyrene may be activated to mitosis-arresting metabolites., (Copyright © 2016 Elsevier B.V. All rights reserved.)