Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urological condition marked by ongoing oxidative stress and persistent inflammation, which complicates clinical management. This study examined the therapeutic effects and underlying mechanisms of 7,8-Dihydroxyflavone (7,8-DHF) in an experimental autoimmune prostatitis (EAP) mouse model, induced via subcutaneous immunization with prostate antigen in Complete Freund's Adjuvant. Mice were administered daily intraperitoneal injections of 7,8-DHF (5 mg/kg) and subsequently underwent a series of evaluations: prostate index measurement, abdominal tactile allodynia assessment using Von Frey filaments, cystometric analysis for urinary function, histological examinations with HE and Masson staining, quantitative PCR for pro-inflammatory cytokines, biochemical assays for oxidative stress markers (MDA, SOD, CAT, total antioxidant capacity), and Western blot analysis to assess activation of the TrkB/AKT/ERK/SIRT3 signaling pathway. 7,8-DHF treatment significantly decreased the prostate index, alleviated pelvic tactile allodynia, and improved bladder function in EAP mice. Histopathological analysis showed notable reductions in inflammatory cell infiltration and collagen deposition, along with decreased expression of pro-inflammatory cytokines (IL-6, IL-17α, MCP-1, IL-1β). Mechanistically, 7,8-DHF enhanced antioxidant capacity by increasing SOD/CAT activities and decreasing MDA levels, which correlated with TrkB phosphorylation, subsequent AKT/ERK pathway activation, upregulated SIRT3 expression, and MnSOD deacetylation. In vitro experiments with RWPE-1 cells demonstrated that 7,8-DHF mitigates LPS-induced oxidative stress and inflammation through mechanisms dependent on SIRT3. Collectively, these findings elucidated that 7,8-DHF could ameliorate CP/CPPS by activating the TrkB/AKT/ERK/SIRT3 signaling pathway to suppress oxidative stress and inflammatory reactions, highlighting its potential value as a novel therapeutic candidate for the clinical management of CP/CPPS.

Urological cancers, including renal, bladder, and prostate cancers, are among the most prevalent solid tumors. The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has spurred its exploration for treating urological cancers. In the past decade, preclinical studies have demonstrated promising antitumor activity of CAR-T cells against urological cancers. Meanwhile, multiple clinical trials are currently underway to evaluate their safety and efficacy. However, significant challenges impede the efficacy of CAR-T cell therapy in urological cancers, including tumor heterogeneity and antigen escape, the immunosuppressive tumor microenvironment (TME), and treatment-related toxicities. To address these limitations, current research efforts are actively explored on several strategies, such as identifying novel target antigens, engineering CAR structurally optimized, and reversing the immunosuppressive TME. This review systematically summarizes these recent research advances for renal, bladder, and prostate cancers. Accumulating evidence supports the therapeutic potential of CAR-T cell therapy for urological cancers. To realize its clinical promise, future research needs focus on design of combinatorial strategies, optimizing the balance between efficacy and toxicity, validating findings in larger and more diverse patient cohorts, and developing more precise, individualized treatment regimens.

This study investigates the relationship between DNA methylation patterns and clinicopathological characteristics in prostate cancer. We performed targeted next-generation sequencing (NGS) on methylation sites linked to prostate cancer and calculated the corresponding methylation rates. Clinical samples were divided into training and prediction sets. In the training set, we utilized unsupervised clustering and Support Vector Machine (SVM) modeling to distinguish between prostate cancer and non-cancer samples. For predictions, K-Nearest Neighbors (KNN) assessed sample similarity, while SVM facilitated classification. Bayesian methods integrated probabilities to predict cancer status and cluster assignments. To address uncertainties identified by Uniform Manifold Approximation and Projection (UMAP), we validated our results using Random Forest Support Vector Machine (RFSVM), which highlighted significant methylation sites for SVM training. Depth-correction methods were applied to mitigate variations in sequencing depth. In the training dataset, the leave-one-out cross-validation (LOOCV) prediction accuracy of RFSVM was 0.85 (AUC: 0.91); for RFSVM-depth, it was 0.83 (AUC: 0.93). The LOOCV prediction accuracy for Bayesian SVM (BSVM) was 0.87 (AUC: 0.94), decreasing to 0.83 (AUC: 0.91) with depth correction. In the test dataset, our Bayesian prediction achieved an accuracy of 0.8793 (sensitivity: 0.8182, specificity: 0.9167), which improved to 0.9655 with depth correction (sensitivity: 1.0, specificity: 0.9444). RFSVM demonstrated an accuracy of 0.8621 (sensitivity: 0.8182, specificity: 0.8889), dropping to 0.7759 with depth correction. Among 58 samples, predictions showed 67

ObjectiveSmoking remains a significant risk factor for prostate, bladder, and kidney cancers. The disease burden and smoking-attributable carcinogenic effects are particularly concentrated in adults aged 40 years and older, making this age group critical for targeted prevention. We aimed to analyze the global, regional, and national disease burden of smoking-attributable prostate, bladder, and kidney cancers exclusively among adults aged 40 years and older from 1990 to 2021, and to provide long-term projections to 2045 for evidence-based tobacco control and cancer prevention strategies.MethodsThis retrospective observational study used data from the Global Burden of Disease Study 2021, we assessed age-standardized mortality rate (ASMR) and disability-adjusted life year rate (ASDR), along with absolute deaths and disability-adjusted life years (DALYs). Trends were evaluated using estimated annual percentage change (EAPC), and future burden was projected using the Nordpred model.ResultsFrom 1990 to 2021, absolute DALYs and deaths increased globally, while ASDR and ASMR declined. In 2021, DALYs for prostate and kidney cancers peaked at ages 65-69, and for bladder cancer at 70-74. High-SDI regions had the highest ASDR for prostate and kidney cancers, while middle-high-SDI regions led in bladder cancer. ASDR and ASMR decreased for prostate and bladder cancers across most SDI regions, but kidney cancer rates rose in Middle and Low-middle-SDI regions. By 2045, prostate cancer ASDR/ASMR are projected to increase after 2035, while bladder and kidney cancers will continue declining, though absolute burden will rise.ConclusionSmoking-attributable urological cancers remain a major public health challenge. Despite declining age-standardized rates, absolute burden is growing, particularly among older adults and in middle/low-SDI regions. Strengthened tobacco control, early screening, and optimized resource allocation are critical to reducing future burden.

Following the publication of this article, the authors have brought to the Editor's attention that they made an error in the compilation of the data in Fig. 4, as it appeared on p. 9. Specifically, some of the blots included for the 769‑P cell line experiments in Fig. 4B had inadvertently been included in the figure incorrectly. The corrected version of Fig. 4, now showing all the correct western blot data in Fig. 4B, is shown on the next page. The authors sincerely apologize for the errors that were introduced during the preparation of this figure, and are grateful to the Editor of Oncology Reports for granting them the opportunity to publish a Corrigendum. All the authors agree with the publication of this Corrigendum, and they also regret any inconvenience that this mistake may have caused. [Oncology Reports 49: 33, 2023; DOI: 10.3892/or.2022.8470].

e17090 Background: The ARASENS trial established that androgen deprivation therapy (ADT) combined with Darolutamide and Docetaxel improves survival in mHSPC. Given the lower chemotherapy tolerance reported in Asian populations and the paucity of Chinese real-world data, The Yi-Huan Genitourinary Cancer Group conducted a multicenter analysis (YHCG-006) to validate the efficacy and safety of this triplet regimen in a Chinese cohort in Zhejiang Province. Methods: We retrospectively analyzed 100 consecutive mHSPC patients (pts) treated with ADT, Darolutamide, and Docetaxel across 18 centers in Zhejiang Province, China (Aug 2022–Jan 2026). Evaluations included baseline characteristics, Docetaxel utilization, PSA dynamics, and treatment-related adverse events (AEs). Results: 100 mHSPC pts were included. The median age was 70 years (range, 43–87). All pts had metastatic disease at baseline, distributed as non-regional lymph nodes (M1a) 12%, bone (M1b) 70% with a median of 8 lesions, and visceral metastasis (M1c) 18%. High-grade histology was common (Gleason score ≥8 in 83%), and performance status was favorable in most (ECOG PS 0–1 in 86%; ECOG PS 2 in 12%). A high-risk classification was present in 80%, and high-volume disease was prevalent (69%). The median baseline PSA was 121.76 ng/ml (IQR, 33.60–375.07). With a median follow-up of 9.2 months (range, 0.8–37.3), ≥6 cycles of Docetaxel were administered in 62% of pts. Dose modifications included Docetaxel reduction in 18 pts (typically to 60 mg/m²) and Darolutamide reduction in 1 patient (to 600 mg/day due to rash). Supportive care included bone-protective agents in 41% and granulocyte colony-stimulating factor (G-CSF) in 32% (prophylactic in 5 pts). At 3 and 6 months, PSA 90 rates were 95.5% (84/88) and 97.8% (90/92), respectively. The proportions achieving PSA < 0.2 ng/ml were 44.3% (39/88) at 3 months and 59.1% (55/93) at 6 months. During follow-up, 67% of pts achieved a nadir PSA < 0.2 ng/ml, and 44% reached an ultra-low nadir PSA < 0.02 ng/ml. The median time to PSA < 0.2 ng/ml was 4.7 months. 9 pts experienced disease progression; median radiographic progression-free survival (rPFS) and overall survival (OS) were not reached at the time of analysis. 38 of 100 pts experienced ≥grade 3 AEs. Neutropenia was the most frequent grade 3 or 4 AE (30 cases), with febrile neutropenia in 13.3% (4/30) of these neutropenia cases. Conclusions: In this real-world Chinese cohort characterized by predominantly high-volume and high-risk disease, Darolutamide-based triplet therapy yielded rapid and deep PSA responses with acceptable toxicity. These findings support the feasibility and clinical utility of this regimen in Chinese mHSPC pts, while underscoring the importance of vigilant monitoring for chemotherapy-related AEs, particularly neutropenia.

Introduction Cystoscopy-based diagnosis and surveillance of bladder cancer (BC) remain challenging. This study presents a urine-based assay that enriches DNA-methylation signals via PCR enrichment and applies a machine-learning model to enable cost-effective early detection. Methods In a prospective cohort at hospital (May 2022-November 2023), 155 individuals were enrolled, BC was diagnosed and confirmed by cystoscopy-guided biopsy and histopathology. Targeted next-generation sequencing of urine DNA quantified methylation at 44 CpG sites within IRF4, PENK and PXDN. Supervised classifiers trained on these features distinguished tumor from non-tumor urine samples. Systems analyses around IRF4/PENK/PXDN mapped signaling pathways, protein interaction modules and tumor-microenvironment contexts in BC. Results Using 155 urine samples (68 BC, 87 non-BC) with methylation and transcript expression data in TCGA-BLCA, we found significantly increased methylation of IRF4, PENK, and PXDN in BC (P < 0.0001). Corresponding mRNA levels of IRF4 and PENK were significantly downregulated in tumor tissues, with PXDN showing a declining trend. Methylation of IRF4 and PXDN negatively correlated with their expression (P < 0.0001). A 41-CpG-site random forest classifier targeting IRF4, PENK, and PXND (BladderCando model) demonstrated excellent performance in distinguishing BC from non-BC individuals (AUC = 0.9783, F1 = 0.9773), outperforming urine cytology for low-grade BC detection. Co-expression and enrichment analyses identified DCN as a central hub gene, primarily linked to ECM functions. High expression of PXDN, IRF4, and DCN correlated with upregulated immune checkpoint genes and increased immune cell infiltration. Single-cell sequencing revealed PXDN in fibroblasts and endothelial cells, DCN in fibroblasts, and IRF4 in T cells, with expression patterns in urine mirroring tumor tissue profiles. Conclusion This study establishes IRF4, PENK and PXDN methylation in urine as robust molecular signatures for BC detection, with machine-learning integration markedly enhancing diagnostic precision. Beyond early surveillance, these epigenetic alterations delineate tumor-microenvironment interactions that may inform future therapeutic strategies.

To investigate the feasibility of Simultaneous Amplification and Testing PCA3 (SAT-PCA3, a urine-based prostate cancer-specific biomarker) combined with conventional clinical information in the diagnosis of prostate cancer (PCa). This retrospective study analyzed 137 patients with complete clinical data. Patients with a biopsy Gleason score ≥ 6 were classified as having PCa. Clinical indicators showing significant differences between PCa and non-PCa groups were identified via univariate analysis. A multivariate model was constructed using pathological diagnosis as the outcome and age, digital rectal exam (DRE) result, prostate-specific antigen (PSA), SAT-PCA3 result, and Prostate Imaging Reporting and Data System (PIRADS) score as predictors. The DeLong test was performed to compare differences in the area under the receiver operating characteristic (ROC) area under the curve (AUC) between the univariate model and the multivariate model. A total of 137 patients were included: 65 were diagnosed with PCa and 72 were non-PCa. Statistical differences existed between the PCa and non-PCa in age, PSA, DRE, PIRADS score, and SAT-PCA3 (p < 0.05). All variables were independently associated with PCa. The coefficient of determination (R2) values is 0.626 in the multivariate model. The AUCs of the age [0.711(95

Prostate cancer (PCa) is a leading malignancy in men, with mortality primarily attributed to progression to castration-resistant prostate cancer (CRPC). Although androgen deprivation therapy (ADT) initially demonstrates efficacy, most advanced patients eventually develop CRPC—a stage characterized by limited treatment options and poor prognosis. Elucidating the molecular mechanisms underlying CRPC transformation therefore represents a research priority. Tumor metabolic reprogramming has emerged as a hallmark of cancer, and among various metabolic pathways, lysophosphatidic acid (LPA)—a bioactive lipid mediator—has been increasingly implicated in PCa progression, particularly CRPC transformation. This review systematically examines LPA metabolic sources and signal transduction mechanisms and explores how LPA promotes CRPC progression through driving proliferation, survival, invasion, therapy resistance, and tumor microenvironment remodeling. Finally, we discuss the potential and challenges of targeting the LPA signaling pathway as a novel therapeutic strategy for CRPC.

Background Transurethral resection of bladder tumor (TURBT) is the standard treatment for non-muscle-invasive bladder cancer (NMIBC), but the high rates of residual tumor and recurrence remain major clinical challenges. This study aimed to evaluate the clinical utility of UroCAD urine test for detecting residual tumor after TURBT and predicting recurrence in high-grade bladder cancer. Methods In this prospective study, 38 patients with high-grade bladder cancer were divided into a single TURBT group (n = 23, followed ≥ 6 months for recurrence) and a second TURBT group (n = 15, repeat resection at 4–6 weeks). Urine samples were collected 7–14 days post-initial TURBT for UroCAD-based chromosomal instability (CIN) analysis. Diagnostic performance was assessed against pathology or recurrence. Results In the single TURBT group, UroCAD showed 80% sensitivity, 88% specificity, area under the ROC curve (AUC) 0.84, negative predictive value (NPV) 88%, and 85% accuracy for predicting recurrence. In the second TURBT group, sensitivity for residual tumor was 0%, specificity 92%, AUC 0.46, NPV 86%, and accuracy 80%. Marked CIN in chromosomes 1,3,7,17 was observed in the single TURBT group and pre-second TURBT subgroup, but significantly decreased after second TURBT. Recurrent copy number variations (CNVs) (5p,20q,10p,12q) were identified in the single TURBT group. Maximum CIN Z-values post-second TURBT were significantly lower than those in the single TURBT group (P < 0.05). Conclusion UroCAD-based CIN detection is a promising non-invasive tool for predicting recurrence in high-grade bladder cancer patients after single TURBT and monitoring treatment response. However, the extremely low sensitivity of UroCAD in detecting residual tumors before second TURBT requires further optimization through larger-scale studies.

Lung adenocarcinoma (LUAD) is a highly prevalent and lethal malignancy. Although F-box and leucine-rich repeat protein 6 (FBXL6), an E3 ubiquitin ligase, has been implicated in tumor progression across certain cancers, its functional role in LUAD remains unclear. In this study, we investigated the oncogenic potential of FBXL6 in LUAD pathogenesis. Bioinformatics analysis of GEO, TCGA, and TNM datasets revealed significant upregulation of FBXL6 in LUAD tissues. Functional studies using FBXL6-knockdown (via shRNA in PC-9 cells) and FBXL6-overexpressing (via plasmid transfection in A549 cells) demonstrated that FBXL6 depletion suppressed cell proliferation, migration, and invasion, whereas its overexpression reversed these effects. In vivo experiments further confirmed that FBXL6 knockdown in PC-9 cells inhibited tumor growth and liver metastasis in BALB/c nude mice following subcutaneous or tail vein injection. Mechanistically, FBXL6 was found to physically interact with cyclin-dependent kinase inhibitor 1C (CDKN1C/p57Kip2) and promote its polyubiquitination and proteasomal degradation, thereby destabilizing this tumor suppressor. Rescue assays validated that CDKN1C mediates the pro-tumorigenic effects of FBXL6 on LUAD cell proliferation and metastasis. Collectively, our findings reveal that FBXL6 drives LUAD progression by ubiquitinating and degrading CDKN1C, highlighting its potential as a therapeutic target for LUAD.

BACKGROUND:The underexplored potential of PD-L1 blockade in advanced renal cell carcinoma highlights an urgent need for novel agents. This trial aimed to compare benmelstobart (a novel PD-L1 inhibitor) plus anlotinib with sunitinib as first-line treatment for advanced renal cell carcinoma. METHODS:ETER100 was a multicentre, randomised, open-label, phase 3 trial conducted at 37 medical sites in China. We included patients aged 18-80 years, who had previously untreated, advanced, clear-cell renal cell carcinoma, and an Eastern Cooperative Oncology Group performance status of 0 or 1. We randomly assigned (1:1) patients to receive either benmelstobart (intravenous, 1200 mg, once every 3 weeks) plus anlotinib (oral, 12 mg, once daily for the first 2 weeks of a 3-week cycle) or sunitinib (oral, 50 mg, once daily for the first 4 weeks of a 6-week cycle) until disease progression, unacceptable toxicity, investigator's decision, or patient withdrawal. Randomisation was done centrally with stratified block randomisation (block size 4) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk. The primary endpoint was progression-free survival as assessed by blinded independent central review according to the Response Evaluation Criteria in Solid Tumours version 1.1 in the full analysis set (ie, randomly assigned patients who received at least one dose of study drug without the violation of key inclusion criteria) and per-protocol set (ie, randomly assigned patients who received at least one cycle of protocol treatment without major protocol violations and had at least one efficacy assessment). In this Article, we report the results of a prespecified interim analysis. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT04523272. FINDINGS:Between Aug 25, 2020, and Feb 6, 2023, we assessed 687 patients for eligibility, 531 (77%) of whom were randomly assigned to receive either benmelstobart plus anlotinib (266 [50%] patients) or sunitinib (265 [50%] patients). 527 (99%) patients were included in the full analysis set (263 [50%] patients who received benmelstobart plus anlotinib and 264 [50%] who received sunitinib). All patients were Chinese (400 [76%] men and 127 [24%] women), with a median age of 60 years (IQR 54-67). As of the cutoff date (Jan 31, 2024), the median follow-up was 22·8 months (IQR 15·2-29·7). In the full analysis set, median progression-free survival was significantly longer with benmelstobart plus anlotinib than with sunitinib (19·0 months [95% CI 15·3-22·8] vs 9·8 months [8·4-12·4]; hazard ratio [HR] 0·53 [95% CI 0·42-0·67]; p<0·0001). In the per-protocol set, median progression-free survival was 19·0 months (16·5-22·8) in the benmelstobart-anlotinib group versus 11·0 months (8·5-13·6) in the sunitinib group (HR 0·55 [0·43-0·70]; p<0·0001). The most common grade 3 or worse treatment-related adverse event was hypertension (occurring in 91 [34%] of 264 patients in the benmelstobart-anlotinib group vs 55 [21%] of 264 in the sunitinib group). Serious treatment-related adverse events occurred in 63 (24%) patients in the benmelstobart-anlotinib group and in 42 (16%) patients in the sunitinib group. In the benmelstobart-anlotinib group, three (1%) deaths occurred due to treatment-related adverse events (one each with cardiac-respiratory arrest, unknown reason, and renal failure) and no deaths occurred in the sunitinib group. INTERPRETATION:Benmelstobart plus anlotinib improved progression-free survival compared with sunitinib among patients with previously untreated, advanced clear-cell renal cell carcinoma. These findings suggest the potential of benmelstobart plus anlotinib as a treatment option for this population. FUNDING:Chia Tai Tianqing Pharmaceutical Group and CSCO Clinical Oncology Research Foundation. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

OBJECTIVE:To study the feasibility of multiple factors in improving the diagnostic accuracy of clinically significant prostate cancer (csPCa). METHODS:A retrospective study with 131 patients analyzes age, PSA, PHI and pathology. Patients with ISUP > 2 were classified as csPCa, and others are non-csPCa. The mpMRI images were processed by a homemade AI algorithm, obtaining positive or negative AI results. Four logistic regression models were fitted, with pathological findings as the dependent variable. The predicted probability of the patients was used to test the prediction efficacy of the models. The DeLong test was performed to compare differences in the area under the receiver operating characteristic (ROC) curves (AUCs) between the models. RESULTS:The study includes 131 patients: 62 were diagnosed with csPCa and 69 were non-csPCa. Statically significant differences were found in age, PSA, PIRADS score, AI results, and PHI values between the 2 groups (all P ≤ 0.001). The conventional model (R2 = 0.389), the AI model (R2 = 0.566), and the PHI model (R2 = 0.515) were compared to the full model (R2 = 0.626) with ANOVA and showed statistically significant differences (all P < 0.05). The AUC of the full model (0.921 [95% CI: 0.871-0.972]) was significantly higher than that of the conventional model (P = 0.001), AI model (P < 0.001), and PHI model (P = 0.014). CONCLUSION:Combining multiple factors such as age, PSA, PIRADS score and PHI, adding AI algorithm based on mpMRI, the diagnostic accuracy of csPCa can be improved.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Lingfeng Wu, Shunliang He, Yi He, Xueping Wang, Linfeng Lu. IC-2 Suppresses Proliferation and Induces Apoptosis of Bladder Cancer Cells via the Wnt/ß-Catenin Pathway. Med Sci Monit, 2018; 24: 8074-8080. DOI: 10.12659/MSM.910742.

Prostate-specific antigen (PSA) testing lacks specificity due to benign conditions. This study assessed whether integrating DNA methylation signatures with PSA metrics improves discrimination of prostate cancer (PCa) from non-PCa cases. Targeted bisulfite sequencing of 74 CpG sites in 9 genes was performed on urine sediment from 194 patients (89 PCa, 105 non-PCa). Patients were stratified by total PSA (tPSA) and free-to-total PSA ratio (%fPSA) into risk groups. Random forest identified discriminatory methylation markers, and support vector machine (SVM), k-nearest neighbor (KNN), and Bayesian models were constructed and validated. PSA-based stratification alone could not reliably distinguish PCa from non-PCa, with 26.80% of patients falling into a diagnostic "gray zone". Twenty CpG sites showed significant differential methylation (p < 0.01). In addition, several CpG loci exhibited methylation differences across PSA risk groups. Models based on random forest-selected markers achieved strong diagnostic performance, with KNN yielding the highest accuracy (AUC > 0.95, 100% specificity), and consistently high sensitivity (> 80%), maintaining strong discriminative power even in PSA "gray-zone" cases. Urine-based DNA methylation profiling enhances the diagnostic accuracy of PCa beyond PSA testing, particularly in cases within the PSA gray zone. Validation in larger independent cohorts is warranted to establish its clinical utility.

Background: Cysteine and Glycine Rich Protein 1 (CSRP1) is a member of the cysteine-rich protein family, characterized by a unique double-zinc finger motif. It plays an important role in development and cellular differentiation. Aberrant expression of CSRP1 has been reported in several malignancies, including prostate cancer and acute myeloid leukemia. However, its function in renal cell carcinoma (RCC) remains unexplored. In this study, we investigated the role of CSRP1 in RCC for the first time. Methods: CSRP1 and programmed death-ligand 1 (PD-L1) expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of CSRP1 overexpression on cellular proliferation, migration, and apoptosis were assessed in vitro through CCK-8, wound healing, and flow cytometry assays. To evaluate the role of CSRP1 in immunotherapy, Balb/c mice were treated with anti-PD-L1 antibody, and tumor growth was monitored. Results: In vitro, overexpression of CSRP1 significantly inhibited proliferation and migration of A498 cells while enhancing their sensitivity to sunitinib treatment. Mechanistically, CSRP1 overexpression downregulated PD-L1 expression in RCC cells. In BALB/c mice inoculated with Renca cells, CSRP1 overexpression led to reduced tumor growth and improved response to anti-PD-L1 therapy. Conclusion: CSRP1 may play a role in regulating cell viability, migration, drug resistance, and possibly innate immunity in RCC. These findings suggest that CSRP1 could increase the efficacy of targeted drugs and immunotherapy in combination treatment strategies for RCC.

Background:Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) represents a prevalent urological disorder characterized by an unfavorable prognosis. Accumulating evidence indicates that suppression of excessive reactive oxygen species (ROS) generation significantly ameliorates its inflammatory manifestations. 7,8-dihydroxyflavone (7,8-DHF), a specific TrkB receptor agonist, which could subsequently trigger downstream signaling pathways such as AKT, demonstrates antioxidant and anti-inflammatory properties across diverse pathological conditions. Nevertheless, its potential therapeutic efficacy against CP/CPPS remains undefined. The aim of this study is to investigate the effects of 7,8-DHF on CP/CPPS and elucidate the underlying mechanisms involved, thereby providing fundamental experimental data for the clinical research of pharmacological interventions for CP/CPPS. Methods:CP/CPPS rat model was established via intraprostatic injection of complete Freund's adjuvant (CFA). Utilizing this experimental prostatitis model, we evaluated the effects of 7,8-DHF on prostate index, mechanical hyperalgesia, prostate histopathology, oxidative stress markers, pro-inflammatory cytokine expression, and immune cell infiltration. Molecular analyses further assessed TrkB/AKT/SIRT3 signaling pathways in RWPE-1 cells. We have cultivated human prostate epithelial cells RWPE-1. In vitro cell models were constructed through lipopolysaccharide (LPS) induction. The effects of 7,8-DHF on LPS-induced cellular damage and inflammatory responses were validated through Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays. Results:At the animal level, 7,8-DHF administration concurrently suppressed CFA-induced elevations in prostate index, mechanical hyperalgesia, inflammatory cell infiltration, and pro-inflammatory cytokine levels, while significantly ameliorating histological damage. At the cellular level, 7,8-DHF attenuates LPS-induced cellular damage and inflammatory responses through mechanisms involving the activation of TrkB/AKT/SIRT3 signaling, augmented antioxidant enzyme activity, mitigated ROS overproduction and pro-inflammatory mediator expression, thus disrupting the "oxidative stress-inflammation" vicious cycle. Conclusions:This study identifies 7,8-DHF as a novel therapeutic agent for CP/CPPS, and the potential role of the TrkB/AKT/SIRT3 pathway in the improvement of CP/CPPS by 7,8-DHF, thereby establishing a foundational basis for future CP/CPPS therapeutics.

Background:Clear cell renal cell carcinoma (ccRCC) is a lethal urological cancer that accounts for a considerable portion of all malignant tumors in adults. Alterations in mitochondrial function and metabolism may influence the onset and progression of ccRCC. This study aims to develop a novel clinical prognostic signature for ccRCC based on mitochondria-associated genes, as well as to identify new potential therapeutic agents for this condition. Methods:A total of 539 ccRCC tumors and 72 normal kidney specimens were analyzed from The Cancer Genome Atlas (TCGA). We created a prognostic signature based on univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) Cox regression. A differential expression analysis, functional enrichment, and assessment of tumor immune cell infiltration were performed. Connectivity Map (CMap) and L1000CDS2 dataset were utilized for potential therapeutic drug identification. Vorinostat was examined for its effects on ccRCC cell proliferation, cell death, migration, and invasion using Cell Counting Kit-8 (CCK-8), lactate dehydrogenase (LDH) release, wound healing, and transwell assays. Results:The prognostic signature, comprising 16 mitochondria-related genes, demonstrated marked changes in overall survival between high- and low-risk groups. Functional analysis implicated immune-related pathways, indicating potential for immunotherapy strategies. Vorinostat, identified through drug screening, exhibited inhibitory implications on ccRCC cell proliferation, migration, and invasion and induced cell death. Conclusions:The constructed prognostic signature provides a valuable tool for patient prognosis prediction. Vorinostat emerges as a promising therapeutic candidate for high-risk ccRCC patients, contributing to a deeper understanding of ccRCC biology and personalized therapeutic interventions.

Five inorganic monoiron(II) carbonyl salts 1-5, fac-M[Fe(CO)(3)I-3](n) (Mn+=Na+ (1), K+ (2), Mg2+ (3), Ca2+ (4), NH4+ (5)) were prepared from the reactions of cis-[Fe(CO)(4)I-2] precursor with the iodo salts (MIn), and developed as CO-releasing molecules (CORMs) for CO therapy of cancer. The decomposition of salts 1 - 5 with CO-release in DMSO, D2O, saline, and phosphonate buffer solution was investigated by the Fourier transform infrared (FTIR) spectroscopic monitoring. The corresponding kinetics for the decomposing of these salts were estimated by abiding by a first-order model. Cytotoxicity of the five salts was assessed on a bladder cancer cell line (RT112) by the methyl thiazolyl tetrazolium (MTT) assays for 24 h, with the half maximal inhibitory concentration (IC50) values of 25-43 mu mol center dot L-1. Notably, varying a counter ion of fac-[Fe(CO)(3)I-3](-) anion from an organic aminium to an inorganic cation unambiguously affects its stability and thus the cytotoxicity. Moreover, a mechanistic probing into the cytotoxicity of fac-[Fe(CO)(3)I-3](-) anion was paved. Interestingly, not only the produced iodine radicals but also the gaseous CO from the decomposition contributed to its cytotoxicity. Particularly, it was found that, with the treatment of the anion, the reactive oxygen species (ROS) level in the mitochondria significantly enhanced, and the mitochondria - related protein expression of Parkin was extremely upregulated. The ferroptosis inhibitor assays of Ferrostatin-1 and Liproxstatin-1 confirmed that these complexes evoked a ferroptosis-involved pathway to contribute to their cytotoxicity. Therefore, a mechanistic understanding of the cytotoxicity of fac-[Fe(CO)(3)I-3](-) anion is proposed, which is stimulated by the decomposing of the anion, and thus manufactures the mitochondria-relevant activities such as fission, energy metabolism, and mitophagy, and evokes a pathway of ferroptosis, to lead severe cellular damage even death.