Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is an age-related condition in men with a poorly defined etiology. Chronic inflammation is increasingly recognized as a key contributor to BPH progression; however, the underlying mechanisms remain incompletely understood. This study aimed to elucidate the role of a TNF-α-induced inflammatory microenvironment in regulating BPH progression. We demonstrated that TNF-α levels were significantly elevated in patients with BPH and positively correlated with key clinical characteristics. In vitro, TNF-α promoted the proliferation of prostatic cells. Mechanistically, TNF-α induced the overexpression of SOX4, which subsequently activated the TGF-β/Smad2/3 signaling axis, thereby enhancing cellular proliferation, promoting epithelial-mesenchymal transition (EMT), and exacerbating fibrosis. Importantly, metformin (Met) treatment reduced the expression levels of relevant inflammatory cytokines in the serum of BPH rats. Further analysis confirmed that Met inhibited the TGF-β/Smad2/3 signaling pathway by downregulating the expression of SOX4, thus suppressing cell proliferation, reversing EMT, alleviating fibrosis, and ultimately exerting anti-BPH effects. Collectively, our findings suggest that TNF-α promotes BPH progression via activation of the SOX4/TGF-β/Smad2/3 axis, while Met exerts therapeutic effects by targeting this pathway. These results highlight SOX4 as a potential therapeutic target for BPH and support the clinical potential of Met in BPH management.

BackgroundEndoscopic enucleation of the prostate (EEP) has emerged as a leading surgical treatment for benign prostatic hyperplasia (BPH), traditionally managed by transurethral resection of the prostate (TURP). EEP involves complete adenoma removal along the surgical capsule and can be performed using different energy sources, such as holmium, thulium, GreenLight and diode lasers, or bipolar electrocautery. This meta-analysis compares the efficacy and safety of EEP versus TURP.MethodsA comprehensive search of MEDLINE, EMBASE, CENTRAL, Web of Science, and Scopus (2003-present) identified randomised controlled trials (RCTs) comparing EEP with TURP in adult males (≥18 years) with BPH. Primary outcomes comprised functional measures (Qmax, PVR, IPSS, QoL, IIEF-5), while secondary outcomes included adverse events (incontinence, bleeding, infection, re-treatment rates, hospital stay duration). Two reviewers independently performed data extraction and assessed risk of bias using the Cochrane RoB2 tool.ResultsTwenty-eight RCTs (n = 3085) met inclusion criteria: 1538 patients underwent EEP and 1547 underwent TURP. EEP was associated with significantly improved IPSS (at 12 months), Qmax (1, 6, 12, 24 months), and PVR (6, 12, 36 months) compared with TURP. Perioperative outcomes favoured EEP, including shorter catheterisation time (MD = -1.12 days), reduced hospital stay (MD = -0.92 days), and lower transfusion rates (RR = 0.22). No significant differences were observed in long-term incontinence or bladder neck contracture, though EEP yielded lower stricture rates (RR = 0.55) and reoperation rates for recurrent BPH (RR = 0.32). Heterogeneity was high in several outcomes, reflecting variability in patient characteristics, enucleation techniques, and surgeon experience.ConclusionsEEP compares favourably with TURP for BPH, providing notable benefits in bleeding control, faster recovery and durable obstruction relief. Anatomical enucleation yields functional outcomes at least equal and often superior to TURP. Energy source choice may reflect resources and surgeon preferences. Future research should distinguish enucleation completeness from energy source.

BackgroundFibrosis constitutes a significant pathophysiological mechanism in the clinical progression of benign prostatic hyperplasia (BPH) and represents a contributing factor to the ineffectiveness of prevailing pharmacological treatments. Emerging evidence suggests a close association between microbial presence and the development of fibrosis. Nonetheless, the potential involvement of microbes within prostatic tissue in the pathogenesis of BPH and prostatic fibrosis, along with the underlying mechanisms, remains unexplored.MethodsUtilizing immunohistochemistry and microbial sequencing, we analyzed the microbes of prostate tissues from BPH patients with different degrees of prostate fibrosis and found that Salmonella enterica (S. enterica) was enriched in the high degree of prostate fibrosis. We developed prostate cell and animal models infected with the lipopolysaccharide of S. enterica (S.e-LPS) to assess its impact on prostate fibrosis. To elucidate the underlying functional mechanisms, we employed molecular biology techniques, including RNA degradation assays, N6-methyladenosine (m6A) dot blotting, RNA immunoprecipitation, and m6A immunoprecipitation.ResultsMicrobial diversity differed between low- and high-fibrosis groups, with S. enterica showing the highest mean abundance among the four species that differed significantly. S.e-LPS was detected in S. enterica-rich prostate tissue and was found to significantly promote cell proliferation, cell contractility, lipid peroxidation, and the induction of ferroptosis. Animal experiments demonstrated that S.e-LPS infection led to pronounced hyperplasia of the prostatic epithelium, with epithelial thickness increasing to 1.57 times that of the sham group, and collagen fibrosis increasing to 2.84 times that of the sham group, thereby exacerbating prostatic tissue fibrosis in rats. In vitro experiments further revealed that S.e-LPS promoted prostate cell fibrosis by inducing ferroptosis. Mechanistically, it was determined that S.e-LPS regulates ferroptosis via AlkB homolog 5 (ALKBH5)-mediated m6A modification, which affects the stability of glutathione peroxidase 4 (GPX4) mRNA, thereby affecting prostatic fibrosis.ConclusionThe findings of this study suggest that S. enterica promotes prostatic fibrosis through ALKBH5-m6A-GPX4-mediated ferroptosis. This research offers novel insights for the development of new therapeutic targets and personalized strategies for the prevention and treatment of BPH from the perspectives of microbes and epigenetics.

Benign prostatic hyperplasia (BPH) is a common condition in older men, with its prevalence increasing as age advances. Chronic inflammation orchestrates oxidative stress to exacerbate BPH. YAP1, which regulates organ size, cellular homeostasis, and tissue fibrosis, can be activated by ROCK1. Given the urgent clinical need for more effective therapies, this study explored whether targeting the ROCK1/YAP1 axis could mitigate BPH progression. Here, rats received in situ adeno-associated virus (AAV) injection to induce prostate-specific YAP1 overexpression. An inflammation-associated experimental autoimmune prostatitis (EAP) model was established by prostate antigen immunisation, followed by treatment with ROCK1 inhibitor fasudil and YAP1 inhibitor verteporfin. Cell models were treated with specific inhibitors to confirm the critical role of YAP1 in modulating mitochondrial function. As a result, YAP1 overexpression was sufficient to induce a pathological BPH phenotype. Specifically, YAP1 activated the inflammatory cascade to provoke an immune response, disrupted proliferation/apoptosis balance to induce tissue hyperplasia, triggered epithelial-mesenchymal transition (EMT) and reactive stroma to drive fibrosis, and promoted NOX4/ROS generation and antioxidant depletion to cause oxidative stress. The inflammation-induced experimental autoimmune prostatitis (EAP) model also presented analogous BPH lesions, which were significantly alleviated when treated with ROCK1 inhibitor fasudil and YAP1 inhibitor verteporfin. Mechanistically, YAP1 activation under inflammatory conditions suppressed SIRT1 expression, thereby exacerbating oxidative stress through the disruption of DRP1/MFN2-mediated mitochondrial dynamics. Overall, inflammation-driven activation of the ROCK1/YAP1 axis aggravates oxidative stress, promoting BPH hyperplasia and fibrosis by impairing SIRT1-regulated mitochondrial dynamics. These findings provide a preclinical rationale for developing ROCK1 or YAP1 inhibitors as targeted therapies for BPH patients with chronic inflammation.