Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function by inducing apoptosis in a rat model of experimental autoimmune prostatitis.

Over the years, numerous epidemiological studies have shown that chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) promotes erectile dysfunction. Nonetheless, the precise underlying mechanism remains to be fully clarified. The objective of this research was to identify crucial signaling pathways responsible for CP/CPPS-induced erectile dysfunction. Thirty 8-week-old male Sprague‒Dawley rats were randomly assigned to either the CP/CPPS model group or the control group. The CP/CPPS rat model was established through subcutaneous injection of a combination of rat prostate protein and Freund's adjuvant. Penile erectile function assessment was conducted 45 days after immunization through electrical stimulation of the cavernous nerve. RNA sequencing of the corpus cavernosum of the penis was then performed using the Kyoto Encyclopedia of Genes and Genomes and protein‒protein interaction network analysis. Western blotting was performed on the cavernous tissue. Cell apoptosis assays, cell counting kit-8 assays, cell cloning assays, and Western blotting were conducted on rat endothelial cells. Erectile function was significantly lower in the CP/CPPS model group than in the control group (p < 0.001). Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that differentially expressed genes were predominantly enriched in the apoptosis pathway. Moreover, an increase in apoptosis in the rat corpus cavernosum, along with a decrease in the protein expression of CD31 (p = 0.0089) and eNOS (p = 0.0069) following CP/CPPS induction, was observed. In a protein‒protein interaction network, Pitx2 was recognized as a central gene. The role of Pitx2 in regulating apoptosis was demonstrated in experiments using rat endothelial cell lines, and it was found to be regulated by the Wnt/ß-catenin pathway. This study highlights the occurrence of cavernous endothelial cell apoptosis in CP/CPPS-induced erectile dysfunction, and the potential mechanism of apoptosis may involve inhibition of the Wnt/ß-catenin/Pitx2 pathway.

Risk factors for distant metastasis and prognosis of the penile cancer with distant metastasis.

Background: Penile cancer (PC) is a rare malignant tumor, whose distant metastasis (DM) is associated with the poorest outcomes. The risk factors associated with DM and prognosis of the PC with DM remain elusive. This study was aimed at investigating risk factors associated with DM and constructing prediction models of PC with DM. Methods: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database over a period of 2000-2020, including clinical characteristics such as age, marital status, tumor size, Tumor Node Metastasis (TNM) staging, and treatment information. Utilizing univariate and multivariate logistic regression, alongside cox regression analysis, we identified independent risk factors for DM and prognosis in the total cases and the cases with DM. Nomograms were developed for predicting DM and prognosis in PC patients. Results: Enrolling 1,488 cases, our study identified tumor size and N stage as independent predictors of DM. The predictive nomogram for DM achieved an area under the curve (AUC) of 0.904. Notably, the 1-, 3-, and 5-year cumulative survival rates for PC with DM were 35%, 17%, and 13%, respectively, with larger tumor size associated with prognosis of PC cases with DM. This study verified a correlation between advanced age and TNM stage, as well as chemotherapy with the poor PC prognosis. The nomogram yielded 0.72, 0.69 and 0.69, in predicting 1-, 3-, and 5-year overall survivals (OS), while 0.73, 0.70 and 0.69 in predicting 1-, 3-, 5-year cancer specific survivals (CSS), respectively. Conclusions: This study investigated risk factors of PC with DM. Also, nomograms for predicting DM, OS and CSS of PC patients were developed.

A comprehensive analysis on the relationship between BDE-209 exposure and erectile dysfunction.

Decabromodiphenyl ether (mainly BDE-209) is a commonly used brominated flame retardant in various industrial products. Although its damage to the reproduction system has been established, its effect on erectile function remains unclear. The present study investigated whether BDE-209 induced erectile dysfunction in male SD rats and the underlying mechanisms. Pubertal male rats were exposed to BDE-209 orally (0, 5, 50, and 500 mg/kg/day) for 28 days and the ICP (intracavernous pressure) and MAP (mean arterial pressure) were measured. After the rats were euthanized, the fibrosis and apoptosis levels were evaluated. Additionally, the endothelial function of the rat vascular endothelium cells and the human umbilical vein endothelial cells were impaired after treatment with 50 µM and 100 µM BDE-209. Moreover, the bioinformatics based on CTD database and ChIP-X Enrichment Analysis, version 3 (ChEA3) and molecular docking analysis demonstrated that 5 transcription factors (NFKB1, NR3C1, E2F5, REL, IRF4) might regulate endothelial function by affecting the expression of interactive genes (BCL-2, CAP3, CAT, TNF, MAPK1, and MAPK3). In summary, the present study demonstrated that BDE-209 might affect downstream interactive genes by binding to transcription factors, leading to corpus cavernosum endothelial dysfunction, thus contributing to erectile dysfunction in rats.