Correlation between metabolic syndrome and periurethral prostatic fibrosis: results of a prospective study.

BACKGROUND: Prostatic fibrosis, characterized by the accumulation of myofibroblasts and collagen deposition, is closely associated with LUTS and may lead to mechanical obstruction of the urethra. Additionally, Metabolic Syndrome (MetS), characterized by central obesity, high blood sugar, lipid metabolism disorders, and hypertension, is increasingly recognized as a proinflammatory condition linked to prostate inflammation. METHODS: Clinical data from 108 subjects who underwent transurethral resection of the prostate or bipolar plasmakinetic enucleation of the prostate were prospectively collected between June 2021 and August 2022. Patients were divided in two groups according to whether or not they had a diagnosis of MetS. Specimens were stained with Masson trichrome and the periurethral prostatic fibrosis extent was evaluated using quantitative morphometry. RESULTS: Forty-three patients (39.8%) were diagnosed with MetS. Patients with MetS showed a significantly greater extent of prostatic fibrosis than the others (68.1 ± 17.1% vs. 42.5 ± 18.2%, P < 0.001), and there was a positive correlation between the number of positive MetS parameters and the extent of prostatic fibrosis (R2 = 0.4436, P < 0.001). Multivariate regression analysis revealed that central obesity (B = 2.941, 95% confidence interval, 1.700-3.283), elevated fasting glucose (B = 1.036, 95% confidence interval, 0.293-1.780), reduced HDL cholesterol (B = 0.910, 95% confidence interval, 0.183-1.636) and elevated triglycerides (B = 1.666, 95% confidence interval, 0.824-2.508) were positively correlated to prostatic fibrosis. Elevated blood pressure, however, was unrelated to prostatic fibrosis (B = 0.009, 95% confidence interval, -0.664-0.683). CONCLUSIONS: The present findings suggest that prostatic fibrosis is positively correlated with MetS and its components including central obesity, elevated fasting glucose, reduced high density lipoprotein cholesterol and elevated triglycerides.

Citrus Flavone Tangeretin Inhibits CRPC Cell Proliferation by Regulating Cx26, AKT, and AR Signaling.

Prostate cancer (PCa) progression depends on the action of androgen receptors (AR). Therefore, preventing ligand-mediated activation of AR is the first-line treatment strategy for metastatic PCa. Androgen deprivation therapy (ADT) can inhibit ligand binding to AR and alleviate PCa progression initially. However, due to the adaptation of PCa and recovery of AR signaling, castration-resistant prostate cancer (CRPC) eventually develops. Exploring novel dietary compounds that can target AR signaling appears to be a viable alternative therapeutic option for CRPC. In the present study, compounds from the citrus fruits were focused upon, which contain various flavonoid ingredients. Key components contained within orange peel, which is frequently used in traditional Chinese medicine, and downstream targets were first analyzed using network pharmacology approach. Notably, it was found that tangeretin, an active ingredient from orange peel, can significantly inhibit CRPC cell (C4-2 and Du145 cells) proliferation and migration whilst also synergistically increasing the sensitivity of CRPC cells to anti-tumor drugs sorafenib or cisplatin. Tangeretin also significantly reduced AR and AKT expressions in C4-2 cells and signal transducer and activator of transcription 3 expression in the androgen-insensitive cell line Du145. In addition, tangeretin increased the expression of both connexin26 (Cx26) and gap junction function, which may mediate the bystander effects of cisplatin or sorafenib. Taken together, the present study revealed a novel molecular mechanism by which tangeretin may inhibit the proliferation of CRPC cells, by affecting the Cx26/AKT/AR pathway, to synergistically increase the sensitivity of CRPC cells to sorafenib and cisplatin.

A novel mouse model simulating transurethral laser vaporization prostatectomy.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-µm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-µm thulium laser.