Hypoxia activates the hypoxia-inducible factor-1α/vascular endothelial growth factor pathway in a prostatic stromal cell line:A mechanism for the pathogenesis of benign prostatic hyperplasia

Background The development of benign prostatic hyperplasia(BPH)is closely related to hypoxia in the prostatic stroma,and the hypoxia-inducible factor-1α/vascular endothelial growth factor(HIF-1α/VEGF)pathway has been shown to significantly activate in response to hypoxia.The underlying mechanism for activation of this pathway in the pathogenesis of BPH remains unclear.Materials and methods We constructed HIF-1αoverexpression and knockdown BPH stromal(WPMY-1)and epithelial(BPH-1)cell lines,which were cultured under different oxygen conditions(hypoxia,normoxia,and hypoxia+HIF-1αinhibitor).Quantitative real-time polymerase chain reaction(qPCR)and Western blotting were applied to detect the expression of the HIF-1α/VEGF pathway.Cell proliferation and apoptosis were analyzed by Cell Counting Kit-8 and flow cytometry.We used the miRWalk 2.0 database and Western blotting to predict the potential miRNA that selectively targets the HIF-1α/VEGF pathway,and verified the prediction by qPCR and dual-luciferase assays.Results In a BPH stromal cell line(WPMY-1),the expression of VEGF was in accordance with HIF-1αlevels,elevated in the overexpression cells and decreased in the knockdown cells.Hypoxia-induced HIF-1αoverexpression,which could be reversed by a HIF-1αinhibitor.Moreover,the HIF-1αinhibitor significantly depressed cellular proliferation and promoted apoptosis in hypoxic conditions,assessed by Cell Counting Kit-8 and flow cytometry.However,in the BPH epithelial cell line(BPH-1),the expression level of HIF-1αdid not influence the expression of VEGF.Finally,a potential miRNA,miR-17-5p,regulating the HIF-1α/VEGF pathway was predicted from the miRWalk 2.0 database and Western blotting,and verified by qPCR and dual-luciferase assay.Conclusions In hypoxia,activation of the HIF-1α/VEGF pathway plays a crucial role in regulating cell proliferation in a BPH stromal cell line.Regulation by miR-17-5p may be the potential mechanism for the activation of this pathway.Regulation of this pathway may be involved in the pathogenesis of BPH.

Construction and evaluation of a novel prognostic risk model of aging-related genes in bladder cancer

Background:Bladder cancer(BLCA)is the most common malignancy of the urinary system.Muscle-invasive bladder cancer(MIBC),which constitutes approximately 25%of all BLCA cases,is characterized by frequent recurrence and early onset of metastasis.Bladder cancer most commonly occurs in elderly patients and is significantly associated with aging.However,the prognostic value of age-related genes in BLCA,especially in MIBC,remains unclear.Materials and methods:Training and testing sets were obtained from The Cancer Genome Atlas BLCA project.Differentially expressed genes between BLCA and normal samples intersected with human aging-related genes.Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were used to identify prognostic aging-related signatures,followed by the construction of a risk score model and nomogram.Kaplan-Meier and receiver operating characteristic analyses were conducted to assess the predictive power.An independent BLCA cohort of 165 samples was included for external validation.The CIBERSORT algorithm was used to explore the characteristics of the immune microenvironment.Results:Seven genes(IGF1,NGF,GCLM,PYCR1,EFEMP1,APOC3,and IFNB1)were identified by Cox and least absolute shrinkage and selection operator analyses.After combining the gene signature with the clinical parameters of patients with BLCA,a risk-prognosis model and nomogram were constructed and validated with the testing set.Bladder cancer cases with high 7-gene signature scores(high-risk group)and low scores(low-risk group)showed distinct prognoses.Furthermore,7 types of immune cells were significantly altered between the low-and high-risk groups.Conclusions:Collectively,our data provide a 7-gene signature that serves as a potential biomarker for BLCA,especially MIBC.Moreover,this 7-gene signature highlights the role of the tumor immune microenvironment in prognosis and thus might be related to the response to anti-programmed cell death protein 1-based immunotherapy.

Ductal adenocarcinoma of the prostate or seminal vesicle adenocarcinoma:An multi-disciplinary team(MDT)case report and literature review

We introduced a 61-year-old male with ductal adenocarcinoma of the prostate who underwent a tortuous diagnosis and treatment.Multi-disciplinary team meetings organized by our hospital have shown great value in the whole process.The patient presented with gross hematuria accompanied by frequent urination initially,and was diagnosed with ductal adenocarcinoma of the prostate involving right seminal vesicle gland and urethra by urethroscopy biopsy.The clinical stage of tumor was T3bN0M0.After 4 cycles of neoadjuvant chemotherapy,the tumor shrank significantly and the patient underwent a laparoscopic radical prostatectomy.But the patient declined to continue chemotherapy postoperatively.After 10 months,the serum prostatic specific antigen increased to 0.05 ng/mL,and multiple metastases were found in the patient's bilateral lungs.However,an unexpected diagnosis of seminal vesicle adenocarcinoma was put forward from another hospital after supplementary pathologic immunohistochemical examination.Then,after careful discussion and demonstration by our multi-disciplinary team experts,we insisted on the diagnosis of ductal adenocarcinoma of the prostate and suggested that the original regimen of chemotherapy should be continued.Up-to-date,14 months after the operation,the patient continues to survive while undergoing ongoing active treatment as recommended.

A short review of male genito-urinary lesions caused by coronavirus disease 2019(COVID-19)

Coronavirus disease 2019(COVID-19)is a novel infectious disease that has spread worldwide since it first appeared in December 2019.It can cause pathologies in several organs of the body through direct and indirect mechanisms.After more than two years of study,the effects of COVID-19 on the genitourinary system are now well-evidenced as COVID-19 has considerable effects on the kidneys,testes,vas deferens,epididymis,seminal vesicles,prostate,and penis.Renal invasion is mainly characterized by acute kidney injury.Testicular invasion is characterized by orchitis,testicular epididymitis,etc.Although COVID-19 has been suspected to spread via serum,evidence for the presence of the virus in the semen of patients is currently scarce.COVID-19 also impacts the sexual function of patients to varying degrees,with some patients developing erectile dysfunction.The underlying mechanisms of COVID-19 invasion into the genitourinary system have not been clearly identified,and more clinical studies are required.This review discusses the impact of COVID-19 on the genitourinary system and male health.