Objectives: 5α‐reductase inhibitor (5‐ARI) is a commonly used medicine in the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Our study mainly focuses on the mechanism of BPH development after 5ARI treatment.Materials and Methods: Prostate specimens from patients were collected. Insulin‐like growth factor 1 (IGF‐1), Beclin‐1, LC3 levels, was analysed by immunohistochemistry. The role IGF‐1 on autophagic flux in prostate epithelial cells was studied. Additionally, effect of autophagy on recombinant grafts consisting of prostate stromal and epithelial cells in nude mice was investigated.Results: We demonstrated that IGF‐1 expression is down‐regulated in prostate fibroblasts after long‐term 5‐ARI application. A decrease in IGF‐1 levels was found to activate autophagic flux through the mTOR pathway in prostate epithelial cells, while the inhibition of IGF‐1 receptor function induced autophagy in prostate epithelial cells. In addition, we revealed that blocking autophagic flux initiation can reduce the volume of recombinant grafts in vivo. Finally, our findings suggest that long‐term 5‐ARI application reduces IGF‐1 secretion by prostatic stromal cells, thereby inducing autophagy of prostatic epithelial cells, which is one of the mechanisms underlying BPH pathogenesis and progression.Conclusions: Focusing on the autophagy induced by low levels of IGF‐1 in prostatic epithelial cells, after elucidating AR signalling impairment of prostate stromal cells, might provide a novel strategy for the treatment and prevention of BPH development.
Benign prostatic hyperplasia (BPH) presents a significant clinical challenge, with conventional therapies carrying substantial risks, including urinary retention, sexual dysfunction, and prolonged recovery. To address the urgent need for safer, ultra-minimally invasive alternatives, we developed a sonosensitizing nanoplatform using copper-manganese-doped mesoporous silica nanoparticles (Cu-Mn@SiO2) for ultrasound-induced sonodynamic therapy (SDT). Here, we demonstrate that this innovative strategy provides highly effective and precisely targeted therapy for BPH. In vitro studies revealed that Cu-Mn@SiO2-mediated SDT significantly amplified intracellular reactive oxygen species (ROS) generation, triggering oxeiptosis characterized by PGAM5 cleavage, mitochondrial membrane depolarization, and mitochondrial damage in both BPH-1 epithelial and WPMY-1 stromal cells. In a testosterone-induced BPH rat model, a Cu-Mn@SiO2-combined, localized SDT treatment resulted in a substantial 60% reduction in prostatic weight and a marked improvement in urinary function. Thermal imaging confirmed prostate-specific hyperthermia without affecting the surrounding tissues. Histopathology revealed reduced collagen deposition and restored glandular morphology with comprehensive biosafety assessments showing no systemic toxicity. By precisely inducing localized oxeiptosis within hyperplastic prostatic tissue via focused ultrasound activation, this Cu-Mn@SiO2-based nanoplatform represents a clinically translatable, ultra-minimally invasive therapeutic strategy offering a superior safety profile for BPH management.
Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge ( p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.