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Ethnopharmacological Relevance: Anemarrhena asphodeloides Bunge (Ane) and Phellodendron chinense C. K. Schneid (Phe) is classical herb pair in traditional Chinese medicine, commonly used to ameliorate the symptoms of Benign Prostatic Hyperplasia (BPH). However, the mechanisms underlying this effect are remained indistinct., Aim of the Study: This study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective., Materials and Methods: Testosterone propionate-induced BPH rat model was established, prostatic parameters, histopathology and the levels of serum dihydrotestosterone (DHT) and testosterone (T) were used to evaluate the pharmacological effect of the herb pair on BPH. Subsequently, untargeted metabolomics of prostate tissues samples was performed by UHPLC-Q-Exactive-Orbitrap-MS, followed by multivariate statistical analysis. Targeted metabolomics by UHPLC-QQQ-MS was further utilized to verify and supplement the results of lipids and amino acids found by untargeted metabolomics, clarifying the relationship between disease, herbal pair and metabolism pathway., Results: The study found that Ane-Phe could relieve the progression of BPH and regulate metabolic imbalances. The levels of 13 metabolites decreased and 11 increased in prostatic tissues including glycerolphospholipid, arachidonic acid, citric acid and so on, these altered metabolites were primarily associated with TCA cycle, arachidonic acid metabolism, lipid metabolism and amino acid metabolism. Furthermore, targeted metabolomics was fulfilled to further analyze the lipid metabolism disorders, the levels of 5 lipids in serum and 21 in prostatic tissues were changed in the herb pair group compared to the model group, which closely related to glycerophospholipid, sphingolipid and glycerolipid metabolism. Besides, amino acid metabolism may be regulated by activating arginine metabolism pathway., Conclusions: In this study, the combination of untargeted metabolomics and targeted metabolomics was applied to explore therapeutic mechanisms of Ane-Phe on BPH. In summary, Ane-Phe could improve the levels of endogenous metabolites by regulating multiple metabolic pathways and plays a role in energy supply, anti-inflammation and oxidative stress in BPH treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad 2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors., (© 2024. The Author(s).)

Chronic prostate inflammation in patients with benign prostate hyperplasia (BPH) correlates with the severity of symptoms. How inflammation contributes to prostate enlargement and/or BPH symptoms and the underlying mechanisms remain unclear. In this study, we utilize a unique transgenic mouse model that mimics chronic non-bacterial prostatitis in men and investigate the impact of inflammation on androgen receptor (AR) in basal prostate stem cells (bPSC) and their differentiation in vivo. We find that inflammation significantly enhances AR levels and activity in bPSC. More importantly, we identify interleukin 1 receptor antagonist (IL-1RA) as a crucial regulator of AR in bPSC during inflammation. IL-1RA is one of the top molecules upregulated by inflammation, and inhibiting IL-1RA reverses the enhanced AR activity in organoids derived from inflamed bPSC. Additionally, IL-1RA appears to activate AR by counteracting IL-1α's inhibitory effect. Furthermore, using a lineage tracing model, we observe that inflammation induces bPSC proliferation and differentiation into luminal cells even under castrate conditions, indicating that AR activation driven by inflammation is sufficient to promote bPSC proliferation and differentiation. Taken together, our study uncovers mechanisms through which inflammation modulates AR signaling in bPSC and induces bPSC luminal differentiation that may contribute to prostate hyperplasia., (© 2024. The Author(s).)

Benign prostatic hyperplasia (BPH) is a histopathologic definition associated with enlargement of the prostate gland that causes obstruction of the lower urinary tract and manifests clinically with characteristic symptoms that are what bring patients for consultation. Urinary tract symptoms are common, especially in an increasingly aging population. Diagnosis and the decision on when and how to treat depend on the patient's quality of life and objective clinical parameters. An individualized, risk-based approach is necessary to guide conservative, pharmacologic, or surgical treatment., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Bladder lesion commonly occurs in patients with benign prostatic hyperplasia (BPH), and the routine screening of bladder lesion is vital for its timely detection and treatment, in which the risk of bladder lesion progression can be effectively alleviated. However, current clinical methods are inconvenient for routine screening. In this study, we proposed a convenient routine screening method to diagnose bladder lesions based on several clinical risk factors, which can be obtained through non-invasive, easy-to-operate, and low-cost examinations. The contribution of each clinical risk factor was further quantitatively analyzed to understand their impact on diagnostic decision-making. Based on a cohort study of 253 BPH patients with or without bladder lesions, the proposed diagnostic model achieved high accuracy using these clinical risk factors. Bladder compliance, maximum flow rate (Qmax), prostate specific antigen (PSA), and postvoid residual (PVR) were identified as the four most important clinical risk factors. To the best of our knowledge, this is the innovative research to predict bladder lesions based on the risk factors and quantitatively reveal their contributions to diagnostic decision-making. The proposed model has the potential to serve as an effective routine screening tool for bladder lesions in BPH patients, enabling early intervention to prevent lesion progression and improve the quality of life., (© 2024. The Author(s).)

Background: Prostate cancer (PCa) usually manifests atypical symptoms in the early stage, and once symptoms appear, most PCa patients have developed to the advanced stage, failing to undergo radical surgery. In this study, PCa occurrence-related biomarkers were explored based on single-cell RNA sequencing (scRNA-seq) data., Methods: scRNA-seq data of prostate normal (Normal), benign prostatic hyperplasia (BPH), and PCa (Tumor) samples were acquired from the Gene Expression Omnibus (GEO). Cellular subsets associated with PCa occurrence were obtained using cell annotation. Additionally, the mRNA expression of nuclear enriched abundant transcript 1 (NEAT1) was detected by quantitative real-time PCR (qRT-PCR). The effects of NEAT1 on cell proliferation and apoptosis were analyzed by 5-ethynyl-2-deoxyuridine (EdU) and flow cytometry. Subsequently, cell-derived xenograft (CDX) models were constructed and divided into the LV-NC and LV-shNEAT1 groups. After the tumor tissues of CDX model mice in each group were extracted, the cell growth and Ki67 expression were observed separately using hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC)., Results: Ten cellular subsets were obtained via cell annotation, and significantly differential changes were observed between Basal intermediate and Luminal during the course of BPH to PCa. NEAT1 - Luminal was highly recruited in the Tumor group with low stemness and high malignancy scores. Matrix metallopeptidase 7 (MMP7) -  keratin 17 (KRT17) - Basal intermediate had high ratios in the Tumor group with low stemness and high malignancy scores. The results of pseudotime analysis revealed that NEAT1 - Luminal in the Tumor group were consistently distributed with tumor stage cells. In vitro assays showed that NEAT1 expression was elevated in PCa cells, and NEAT1 knockdown could inhibit cell proliferation and induce apoptosis. CDX assays indicated that silencing NEAT1 could reduce the growth rate of PCa tumor volume in CDX model mice. H&E staining results showed that nuclei of tumor cells were reduced and exhibited lighter color in the LV-shNEAT1 group compared with the LV-NC group. IHC results showed that Ki67 positivity was significantly lower in the LV-shNEAT1 group than in the LV-NC group., Conclusion: NEAT1 expression is increased in PCa, and NEAT1 can be a potential biomarker and therapeutic target for PCa., (© 2024. The Author(s).)

Purpose: The aim of our study is to assess the differences in functional outcomes during the perioperative and postoperative period after RASP depending on BPH volume., Methods: We searched 2 databases: MEDLINE (PubMed) and Google Scholar using the following search query: robot* AND "simple prostatectomy". The search strategy and review protocol are available at Prospero (CRD42024508071)., Results: We included 25 articles published between 2008 and 2023. Preoperatively, patients with prostate size < 100 cm 3 had more severe symptoms while postoperatively all of them had only mild lower urinary tract symptoms (LUTS). In larger BPH, two authors reported moderate LUTS after RASP: Fuschi [1] (mean IPSS 8.09 ± 2.41) and Stolzenburg [2] (mean IPSS 8 ± 2.7). Postoperative Qmax was also noticeably higher in smaller BPH (mean value range 28.5-55.5 ml/s) compared to larger BPH (mean Qmax 18-29.6 ml/s), although in both groups it was within the normal range. Postoperative post-void residual (PVR) was normal as well except in one study by Stolzenburg et al. [2]. Blood loss was comparable between the groups. The complications rate in general was low., Conclusion: RASP is effective in terms of subjective and objective urination indicators, and a safe procedure for BPH. In the lack of data on implementation of RASP in small prostate volumes, this procedure can be seen as an upper size «limitless» treatment alternative. Currently, comparative data regarding prostate volume is lacking, and future trials with subgroups analysis related to BPH volume might help to address this issue., (© 2024. The Author(s).)

Background: The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer-associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that in combination with conventional chemotherapy are likely to have better patient outcome., Methods: Fibroblasts have been derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer. RNA from these has been used to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts., Results: The study has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts. Also, 15 potential lincRNA-miRNA-mRNA combinations have been identified which may be potential biomarkers., Conclusions: This study identified differentially expressed markers between normal and cancer-associated fibroblasts that would help in targeted therapy against CAFs/derived factors, in combination with conventional therapy. However, this would in future need more experimental validation., (© 2024. The Author(s).)

Benign prostatic hyperplasia (BPH) is a common condition marked by the enlargement of the prostate gland, which often leads to significant urinary symptoms and a decreased quality of life. The development of clinically relevant animal models is crucial for understanding the pathophysiology of BPH and improving treatment options. This study aims to establish a patient-derived xenograft (PDX) model using benign prostatic tissues to explore the molecular and cellular mechanisms of BPH. PDXs were generated by implanting fresh BPH (transition zone) and paired normal (peripheral zone) prostate tissue from 8 patients under the renal capsule of immunodeficient male mice. Tissue weight, architecture, cellular proliferation, apoptosis, prostate-specific marker expression, and molecular profiles of PDXs were assessed after 1 week and 1, 2, or 3 months of implantation by immunohistochemistry, enzyme-linked immunosorbent assay, transcriptomics, and proteomics. Responses to finasteride, a standard-of-care therapy, were evaluated. PDXs maintained histologic and molecular characteristics of the parental human tissues. BPH, but not normal PDXs, demonstrated significant increases in weight and cellular proliferation, particularly at 1 month. Molecular profiling revealed specific gene and protein expression patterns correlating with BPH pathophysiology. Specifically, an increased immune and stress response was observed at 1 week, followed by increased expression of proliferation markers and BPH-specific stromal signaling molecules, such as BMP5 and CXCL13, at 1 month. Graft stabilization to preimplant characteristics was apparent between 2 and 3 months. Treatment with finasteride reduced proliferation, increased apoptosis, and induced morphologic changes consistent with therapeutic responses observed in human BPH. Our PDX model recapitulates the morphologic, histologic, and molecular features of human BPH, offering a significant advancement in modeling the complex interactions of cell types in BPH microenvironments. These PDXs respond to therapeutic intervention as expected, providing a valuable tool for preclinical testing of new therapeutics that will improve the well-being of BPH patients., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to evaluate the effects of chrysin on the ventral prostate of spontaneously hypertensive rats (SHR). Ten-week-old male Wistar and SHR rats received 100 mg/kg/day of chrysin (TW and TSHR) or 200 µL/day of the dilution vehicle (CW and CSHR) for 70 days. After the treatment, the animals were euthanized and the prostates were dissected out, fixed, and processed for further morphological, immunohistochemical, and biochemical analyses. Blood was collected for serological analysis. Chrysin did not interfere with the blood pressure. Morphologically, the epithelial height increased in TW and decreased in TSHR. Stereology showed an increase in the epithelial and stromal relative frequency, and a decrease in the lumen of TW, whereas the epithelium in TSHR was reduced. Normal alveoli decreased, and hyperplastic alveoli had an increment in TW, whereas in TSHR normal alveoli increased and intense hyperplasia decreased. The secretion area was reduced in TW. Immunohistochemical analysis showed a smaller number of PCNA-positive cells in TW. Finally, the biochemical analysis showed a reduction in malondialdehyde, carbonylated proteins, superoxide dismutase, and catalase in TW and TSHR. We concluded that the chrysin effect is dependent on the context in which this flavonoid is employed. In normal conditions, the anabolic potential of the chrysin was favored, disrupting the morphology of the prostate. However, when used in animals predisposed to develop hyperplasia, this flavonoid attenuates the hyperplastic status, improving the morphology of the gland., (© 2024 International Federation of Cell Biology.)

Background: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS., Methods: To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed., Results: NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration., Conclusions: These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Ethnopharmacological Relevance: Many ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established., Aim of the Study: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats., Materials and Methods: The study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined., Results: Ethyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology., Conclusions: EFPET could be useful in the treatment of BPH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Tumor heterogeneity results in aggressive cancer phenotypes with acquired resistance. However, combining chemical treatment with adjuvant therapies that cause cellular structure and function perturbations may diminish the ability of cancer cells to resist at chemical treatment and lead to a less aggressive cancer phenotype. Applied treatments on prostate hyperplasia primary cell cultures exerted their antitumor activities through mechanisms including cell cycle blockage, oxidative stress, and cell death induction by flow cytometry methods. A 5.37 mM Chloramphenicol dose acts on prostate hyperplasia cells by increasing the pro-oxidant status, inducing apoptosis, autophagy, and DNA damage, but without ROS changes. Adding 6.30 mM vitamin C or 622 µM vitamin E as a supplement to 859.33 µM Chloramphenicol dose in prostate hyperplasia cells determines a significant increase of ROS level for a part of cells. However, other cells remain refractory to initial ROS, with significant changes in apoptosis, autophagy, and cell cycle arrest in G0/G1 or G2/M. When the dose of Chloramphenicol was increased to 5.37 mM for 6.30 mM of vitamin C, prostate hyperplasia cells reacted by ROS level drastically decreased, cell cycle arrest in G2/M, active apoptosis, and autophagy. The pro-oxidant action of 1.51 mM Erythromycin dose in prostate hyperplasia cell cultures induces changes in the apoptosis mechanisms and cell cycle arrest in G0/G1. Addition of 6.30 mM vitamin C to 1.51 mM Erythromycin dose in hyperplasia cell cultures, the pro-oxidant status determines diminished caspase 3/7 mechanism activation, but ROS level presents similar changes as Chloramphenicol dose and cell cycle arrest in G2/M. Flow cytometric analysis of cell death, oxidative stress, and cell cycle are recommended as laboratory techniques in therapeutic and diagnostic fields., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

To study the clinical correlation between fasting plasma glucose, lipid metabolism, prostate-specific antigen and prostate volume in patients with benign prostatic hyperplasia, and to explore the combined effect as diagnostic indicators. A total of 108 patients with benign prostatic hyperplasia treated in Beijing University of Chinese Medicine Third Affiliated Hospital from June 2021 to March 2023 were retrospectively analyzed as the hyperplasia group, and 98 healthy physical examination personnel were selected as the control group during the same period. Compare the differences in levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), small and dense low-density lipoprotein cholesterol (sdLDL-C), homocysteine, lipoprotein a (LPa), prostate specific antigen (PSA), and free prostate specific antigen (fPSA) between two groups of patients. Using Pearson analysis method to analyze the correlation between the above indicators and the size of prostate volume in patients with benign prostatic hyperplasia; using multiple linear regression to analyze the influencing factors of prostate volume enlargement; draw receiver operating characteristic (ROC) curves and analyze the application value of individual and combined detection of HDL, FPG, PSA, and fPSA. The results showed that there were significant differences in HDL, FPG, PSA, and fPSA levels between the control group and the proliferative group( P <0.05). The size of prostate volume is negatively correlated with HDL( r =-0.183, P <0.05) and positively correlated with FPG ( r =0.202, P <0.05), PSA( r =0.412, P <0.05), and fPSA( r =0.425, P <0.05). The results of multiple linear regression analysis showed that HDL( P =0.000), FPG( P =0.048), PSA( P =0.044), and fPSA ( P =0.012) were risk factors for increased volume of benign prostatic hyperplasia; ROC curve analysis shows that the AUC of HDL, FPG, PSA, and fPSA combined detection is 0.823, which is better than individual detection. In conclusion,HDL, FPG, PSA, fPSA has close correlation with hyperplasia of prostate, the joint detection may has better prediction for benign prostatic hyperplasia.

Anti-inflammatory and antioxidant effects play crucial roles in the recovery of benign prostatic hyperplasia (BPH). Wenshenqianlie (WSQL) capsule, a typical traditional Chinese medicine formulation combining 14 Chinese herbs, has been reported to exert tonic effects on the kidneys and improve clinical symptoms of BPH. However, its potential antioxidative and anti-inflammatory properties and effects on the improvement of hormone levels have not been reported in depth. In this study, mice were subcutaneously injected with TP (5 mg/kg·d -1 ) to induce BPH. Forty-eight adult BALB/c male mice were randomly allocated to six groups based on the type of drug administered by gavage: control, BPH, BPH+WSQL (40 and 80 mg/kg·d -1 ), BPH+finasteride (1 mg/kg·d -1 ), and WSQL-only treated (80 mg/kg·d -1 ). We investigated the anti-inflammatory and antioxidant effect and mechanism of WSQL on BPH via histopathological examination, immunohistochemistry, enzyme-linked immunosorbent assay, and western blotting combined with in vivo serum metabolomics, gut microbiomics analysis. WSQL alleviated prostate hyperplasia and reduced prostate-specific antigen, dihydrotestosterone, testosterone, and inflammation levels. Gut microbiomics and serum non-targeted metabolomics determined that the protective effect of WSQL against BPH may be related to the improvement of inflammation and testosterone-related gut microbiota and serum metabolites. Further studies showed that WSQL ameliorated nuclear factor-kappa B, its downstream inflammatory factors, and nuclear factor E2-related factor 2 pathway.

Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with >  = 30 s treatment time, with a corresponding maximum reduction in stiffness of -90.9 ± 7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288 s (-91.6 ± 6.0(s.d.)%), and low-PRF CH achieved a (-82.1 ± 5.1(s.d.)%) reduction in stiffness at dose >  = 144 s. Receiver operating characteristic curve analysis showed that a >  ~ 75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression., (© 2024. The Author(s).)

Objective: We conducted a study to assess the effectiveness and safety of three different surgical instruments for enucleation in treating high-risk benign prostatic hyperplasia (BPH). These instruments include red laser, green laser, and plasma surgical equipment for enucleation of the prostate., Method: In a retrospective analysis, 237 patients diagnosed with high-risk benign prostatic hyperplasia (BPH) underwent prostate enucleation using three different groups of surgical instruments at the Department of Urology, the First Affiliated Hospital of Jinzhou Medical University. These groups included the red laser device group (n = 67), the green laser device group (n = 61), and the plasma device group (n = 109). The study evaluated changes in prostate mass, blood loss, operation time, and postoperative efficacy at 1- and 6-month intervals, as well as any associated complications., Results: The red and green laser surgical instrument groups demonstrated superiority over the plasma group in several aspects. (1) Operation Time: *1* Red laser group: 87.9 ± 14.7 minutes; *1* Green laser group: 86.1 ± 15.3 minutes. (2) Blood Loss: *1* Red laser group: 30.1 ± 5.9 mL; *2*Green laser group: 30.9 ± 6.1 mL. (3) Temporary Urinary Incontinence: *1*Red laser group: 3 cases (4.48%); *2*Green laser group: 2 cases (3.28%). These differences were statistically significant. Additionally, postoperative indicators such as IPSS(International Prostate Prostate Symptom Score), QoL(Quality of Life), Q max(The Maximum Flow Rate), and RUV(Residual Urine Volume) showed significant improvement in all three groups compared to the preoperative state., Conclusion: Red laser, green laser and plasma surgical devices were safe and effective in the treatment of high critical benign prostatic hyperplasia; laser surgical devices showed better performance in terms of operation time, intraoperative bleeding and complications.

Objective: Benign prostatic hyperplasia is common in the aging population and frequently comorbid with localized prostate cancer. Large prostate volume places significant challenges in robotic prostatectomy including reduced mobility and visualization. The goal of this study is to evaluate the effect of prostate volume as a continuous variable on cancer specific outcomes., Methods: Three thousand four hundred and twenty five patients with localized prostate cancer at a single institution who underwent robotic prostatectomy were retrospectively reviewed. A number of preoperative, operative, and postoperative variables were collected to evaluate cancer specific outcomes including pathologic stage, tissue margins, and biochemical recurrence (BCR). Logistic regression models and univariate and multivariate analyses were implemented for pathologic stage T3 and BCR respectively., Results: The median follow up time was 52 months (IQR 18-95). 37.4% of the patients had a final pathologic stage of T3 or higher, 21.2% experienced positive surgical margins, and 24.7% of patients experienced BCR. Prostate size was a significant predictor of all three outcomes of interest. Increasing prostate size was protective against both higher pathologic stage and positive surgical margins (odds ratio = 0.989, 0.990 respectively, p < 0.001). There was a modest increase in the risk of BCR with increasing gland size (hazard ratio = 1.006, p < 0.001). These results were most significant for patients with Gleason Grade Groups 1 and 2 prostate cancer., Conclusion: Prostate size is a commonly determined clinical factor that effects both surgical planning and cancer specific outcomes. Increasing prostate size may offer protection against higher stage disease and positive surgical margins. While surgically challenging, favorable oncologic outcomes can be consistently achieved for patients with low-intermediate risk disease., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Benign prostatic hyperplasia (BPH), characterized by the non-malignant enlargement of the prostate, exhibits a pronounced association with inflammation resulting from androgen receptor (AR) deficiency. Ferroptosis, a cell death mechanism triggered by iron-dependent lipid peroxidation and closely linked to inflammation, has yet to be fully understood in the context of BPH. Using RNA sequencing, we observed a significant elevation of taurine-upregulated gene 1 (TUG1) long noncoding RNA (lncRNA) in BPH tissues compared to normal prostate tissue. High levels of TUG1 exhibited a discernible correlation with both prostate volume and the extent of inflammatory infiltration in BPH patients. The suppression of TUG1 not only led to a reduction in prostate size but also ameliorated AR-deficiency-induced prostatic hyperplasia. Mechanistically, a decrease in AR in prostate luminal cells prompted macrophage aggregation and the release of IL-1β, subsequently fostering the transcription of TUG1 via MYC. Induced TUG1, through competitive binding with miR-188-3p, facilitated the expression of GPX4, thereby diminishing intracellular ROS levels and impeding ferroptosis in prostate luminal cells. Notably, the ferroptosis inducer JKE-1674 alleviated inflammation-induced prostatic hyperplasia in vivo. Together, these findings suggest that AR deficiency crucially inhibits ferroptosis, promoting BPH via the TUG1/miR-188-3p/GPX4 signaling axis, and making ferroptosis induction a promising therapeutic strategy for BPH patients with AR deficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The unmet challenge in prostate cancer (PCa) management is to discriminate it from benign prostate hyperplasia (BPH) due to the lack of specific diagnostic biomarkers. Contemporary research on potential PCa biomarkers is directed toward methylated cell-free DNA (cfDNA) from liquid biopsies since epigenetic mechanisms are strongly involved in PCa development., Methods: In the present research, cfDNA methylation of the LGALS3 gene in blood and seminal plasma of PCa and BPH patients was assessed using pyrosequencing, as well as LGALS3 DNA methylation in tissue biopsies. Liquid biopsy samples were taken from patients with clinical suspicion of PCa, who were subsequently divided into two groups, that is, 42 with PCa and 55 with BPH, according to the histopathological analysis., Results: Statistically significant higher cfDNA methylation of LGALS3 in seminal plasma of BPH than in PCa patients was detected by pyrosequencing. ROC curve analysis showed that it could distinguish PCa and BPH patients with 56.4% sensitivity and 70.4% specificity, while PSA did not differ between the two patient groups. In contrast, there was no statistically significant difference in LGALS3 cfDNA methylation in blood plasma between the two patient groups. In prostate tumor tissue, there was a statistically significant DNA hypermethylation of LGALS3 compared to surrounding nontumor tissue and BPH tissue., Conclusions: The DNA hypermethylation of the LGALS3 gene represents an event specific to PCa development. In conclusion, LGALS3 cfDNA methylation in seminal fluid discriminates early PCa and BPH presenting itself as a powerful novel PCa biomarker highly outperforming PSA., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

Background: The top-down holmium laser enucleation of the prostate (HoLEP) technique recently emerged as a safe and effective modification of traditional HoLEP. In our randomized controlled trial, we compared intraoperative and postoperative outcomes of traditional and top-down HoLEP for the treatment of benign prostatic hyperplasia (BPH) in patients with a prostate size ≥80 g., Methods: One-hundred patients with BPH and a prostate volume ≥80 cc participated in this prospective randomized controlled trial. Outcome measures were collected and compared, including IPSS, QoL, flow rate, PVR, IIEF-15, PSA, and TRUS prostate volume changes. Perioperative complications were also recorded. All patients were followed up at 1, 3, 6, and 12 months., Results: There were no significant differences in preoperative baseline characteristics between the two surgical groups. The median prostate volume for the traditional and top-down HoLEP groups was 107 and 102 cc, respectively. The operative parameters and postoperative outcomes were comparable for both cohorts. The median enucleation time for traditional HoLEP was 60 min, which was not significantly longer than that of top-down HoLEP (52 min) (p = 0.07). At 3 months follow-up, there was no statistically significant difference in transient stress urinary incontinence (SUI) in the traditional HoLEP (4.1%) versus the top-down HoLEP group (2.2%), (p = 0.61). There were no significant differences in functional and sexual outcomes between the two groups at 12 months., Conclusions: The HoLEP procedure significantly improves patients' urinary functional outcomes and has comparable postoperative outcomes regardless of the technique utilized., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Surgical treatment of symptomatic benign prostatic hyperplasia (BPH) has seen an evolution during the last decades. On one hand, en-bloc HoLEP emerged as a valid endoscopic treatment regardless prostate size. On the other hand, robot-assisted simple prostatectomy (RASP) has gained attention in larger prostates showing encouraging results. Herein, for the first time in the scientific scenario, we sought to compare the outcomes of RASP and en-bloc HoLEP cases after propensity-score matching (PSM) analysis., Methods: We retrospectively queried our prospectively database of patients treated with HoLEP or RASP between 2017 and 2022 among two high-volume centers. PSM was applied based on the International Prostate Symptom Score (IPSS) questionnaire, prostate volume and max-flow rate. All procedures were performed by a single surgeon per center. Outcomes were assessed at 1, 3, and 6-month postoperatively and therefore annually. Trifecta definition was used to assess "success" in surgical procedures and was defined as the contemporary presence of: a) no postoperative complications within the first postoperative month; b) 1-month postoperative Qmax >15 ml/s and c) no urinary incontinence at 3-month evaluation., Results: Overall, 48 HoLEP and 47 RASPs were matched. Operative time, hospitalization time (median 4 vs 5 days) and catheterization time (median 3 vs 2 day) were found to be shorter in the HoLEP group as compared to the counterpart (p < 0.05). Early postoperative complication rate was also lower in the HoLEP cohort (6.2% vs 12.6%; p = 0.03) as well as postoperative haemoglobine blood level drop (1.4 vs 2.4 g/dL; p = 0.03). On the other hand, postoperative antegrade ejaculation (55.3% vs 6.8%) 1-month max flow (median 28 vs 24 ml/sec) and continence rates (0% vs 20.8%) favored RASP (p < 0.05). Overall, Trifecta rate was similar in the two groups (76.1% vs 82.6%)., Conclusion: Both HoLEP and RASP are safe and effective treatments for symptomatic BPH. HoLEP demonstrated to have lower perioperative risks while is affecting by a higher probability of transient early UI. On the other hand, RASP is more effective in reducing postoperative ejaculatory dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, β (ERα,β) and prostate-specific antigen (PSA)., Materials and Methods: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted., Results: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERβ expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERβ expression levels., Conclusion: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).

Benign prostatic hyperplasia (BPH) is a prevalent disease among middle-aged and elderly males, but its pathogenesis remains unclear. Dysbiosis of the microbiome is increasingly recognized as a significant factor in various human diseases. Prostate tissue also contains a unique microbiome, and its dysbiosis has been proposed to contribute to prostate diseases. Here, we obtained prostate tissues and preoperative catheterized urine from 24 BPH individuals, and 8 normal prostate samples as controls, which followed strict aseptic measures. Using metagenomic next-generation sequencing (mNGS), we found the disparities in the microbiome composition between normal and BPH tissues, with Pseudomonas significantly enriched in BPH tissues, as confirmed by fluorescence in situ hybridization (FISH). Additionally, we showed that the prostate microbiome differed from the urine microbiome. In vitro experiments revealed that lipopolysaccharide (LPS) of Pseudomonas activated NF-κB signalling, leading to inflammation, proliferation, and EMT processes, while inhibiting apoptosis in prostatic cells. Overall, our research determines the presence of microbiome dysbiosis in BPH, and suggests that Pseudomonas , as the dominant microflora, may promote the progression of BPH through LPS activation of NF-κB signalling.

Our study highlights the apoptosis, cell cycle, DNA ploidy, and autophagy molecular mechanisms network to identify prostate pathogenesis and its prognostic role. Caspase 3/7 expressions, cell cycle, adhesion glycoproteins, autophagy, nuclear shrinkage, and oxidative stress by flow-cytometry analysis are used to study the BPH microenvironment's heterogeneity. A high late apoptosis expression by caspases 3/7 activity represents an unfavorable prognostic biomarker, a dependent predictor factor for cell adhesion, growth inhibition by arrest in the G2/M phase, and oxidative stress processes network. The heterogeneous aggressive phenotype prostate adenoma primary cell cultures present a high S-phase category (>12%), with an increased risk of death or recurrence due to aneuploid status presence, representing an unfavorable prognostic biomarker, a dependent predictor factor for caspase 3/7 activity (late apoptosis and necrosis), and cell growth inhibition (G2/M arrest)-linked mechanisms. Increased integrin levels in heterogenous BPH cultures suggest epithelial-mesenchymal transition (EMT) that maintains an aggressive phenotype by escaping cell apoptosis, leading to the cell proliferation necessary in prostate cancer (PCa) development. As predictor biomarkers, the biological mechanisms network involved in apoptosis, the cell cycle, and autophagy help to establish patient prognostic survival or target cancer therapy development.

Background: We aimed to determine if preoperative prostate volume-enucleated weight concordance predicts short-term anatomical endoscopic enucleation of the prostate (AEEP) outcomes using the REAP international database., Methods: 649 patients with data on both preoperative ultrasound-derived prostate volume and enucleated specimen weight were analyzed. Linear regression was used to investigate the effect of volume-weight concordance on postoperative outcomes. Model residuals were used to divide the cohort into 3 centiles: (1) less-than-expected enucleated specimen weight; (2) appropriate concordance between prostate volume and specimen weight; (3) more-than-expected specimen weight. Outcomes were also analyzed with only enucleated weight as a predictor (comparing ≤ 80 g and > 80 g)., Results: There was a trend towards more-than-expected enucleated specimen weight with increased age (p = 0.006). There was an increasing trend of operation time (p = 0.012) and enucleation time (p = 0.015) as specimen weight increased, and a decreasing trend of postoperative acute urinary retention (p = 0.005). Laser type, enucleation method, and early apical release were similar. In correlation analysis, greater-than-expected prostate weight was associated with greater Qmax improvement at 3 months. Prostate weight alone did not appear to be a significant predictor of outcomes., Conclusions: If enucleated specimen weight is more than expected according to preoperative ultrasound volume measurement, greater Qmax improvement and less postoperative acute urinary retention is expected. Although precision may be limited by ultrasound approximation and inexact specimen weight measurements, these shortcomings are similar in real-world clinical practice. Overall, preoperative prostate volume and actual enucleated specimen weight should be interpreted in the context of each other to predict clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Benign prostatic hyperplasia unresponsive to medical treatment is an important problem for elderly patients. Although the gold standard surgical treatment is monopolar transurethral resection of the prostate (MTURP), postoperative complications are still a concern., Aim: The aim of this study was to determine which transurethral prostate resection (TURP) methods are more effective and safer in elderly patients., Methods: Patients who underwent TURP in our clinic between 2012 and 2021 were analyzed retrospectively and divided into three groups according to their ages. Patients were treated with MTURP (n = 169) and bipolar transurethral resection of the prostate (BTURP) (n = 1152). Pre- and post-operative data for age groups were compared according to TURP methods., Results: The resection speed in the BTURP method was statistically significantly faster in groups 2 and 3 (P < 0.05). Although not statistically significant (P > 0.05), there was a numerically smaller decrease in hemoglobin (Hb) value in group 2 and a numerically greater decrease in post-voiding residual (PVR) volume in groups 1 and 3 in the BTURP method. The increase in maximum urine flow (Qmax) was significantly higher only in group 2 (P = 0.032), but it was numerically higher in all groups in the BTURP method., Conclusion: The results of this study showed that BTURP was at least as effective and safe as MTURP in geriatric patients and also better in terms of Hb decrease, resection speed, Qmax increase, and PVR volume decrease., (Copyright © 2024 Copyright: © 2024 Nigerian Journal of Clinical Practice.)

Background: Apart from antagonizing ß-adrenoceptors, carvedilol antagonizes vascular α 1 -adrenoceptors and activates G protein-independent signaling. Even though it is a commonly used antihypertensive and α 1 -adrenoceptors are essential for the treatment of voiding symptoms in benign prostatic hyperplasia, its actions in the human prostate are still unknown. Here, we examined carvedilol effects on contractions of human prostate tissues, and on stromal cell growth., Methods: Contractions of prostate tissues from radical prostatectomy were induced by electric field stimulation (EFS) or α 1 -agonists. Growth-related functions were examined in cultured stromal cells., Results: Concentration-response curves for phenylephrine, methoxamine and noradrenaline were right shifted by carvedilol (0.1-10 µM), around half a magnitude with 100 nM, half to one magnitude with 1 µM, and two magnitudes with 10 µM. Right shifts were reflected by increased EC 50 values for agonists, with unchanged E max values. EFS-induced contractions were reduced by 21-54% with 0.01-1 µM carvedilol, and by 94% by 10 µM. Colony numbers of stromal cells were increased by 500 nM, but reduced by 1-10 µM carvedilol, while all concentrations reduced colony size. Decreases in viability were time-dependent with 0.1-0.3 µM, but complete with 10 µM. Proliferation was slightly increased by 0.1-0.5 µM, but reduced with 1-10 µM., Conclusions: Carvedilol antagonizes α 1 -adrenoceptors in the human prostate, starting with concentrations in ranges of known plasma levels. In vitro, effect sizes resemble those of α 1 -blockers used for the treatment of voiding symptoms, which requires concentrations beyond plasma levels. Bidirectional and dynamic effects on the growth of stromal cells may be attributed to "biased agonism"., (© 2024. The Author(s).)

Aims: Benign prostatic enlargement (BPE) can impact lower urinary tract function due to its potential progression to benign prostatic obstruction (BPO). Treatment options include removal of the obstruction by surgery or through use of therapeutics designed to slow growth or reduce tissue stress imposed by muscular stromal components. Inflammation and development of fibrosis can also raise intrinsic tissue stress within the gland, further impacting obstruction. Outflow tract obstruction can also impact emission and ejaculation if the obstruction persists., Methods: This review summarizes an ICI-RS think tank considering novel drug treatments that might address BPO caused by progressive development of BPE, as well as manage decompensation changes to bladder function., Results: Topics included recent advances in our understanding of pathological changes occurring to the prostate and other lower urinary tract tissues during progressive development of BPE, and how prevention or reversal might benefit from the identification of novel drug targets. These included contractile properties of prostatic tissues, the impact of BPE and its effects on bladder function, the deposition of intramural fibrotic tissue with protracted BPO, the role of inflammation in the development of BPE and its progression to BPO. In particular, we discussed current therapeutic options for treating BPE/BPO, and new therapeutic targets, what they treat and their advantage over current medications., Conclusion: Several new drug targets were identified, including soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO•), and sGC activators that promotes sGC-mediated cGMP production when sGC is inactivated and unresponsive to NO•., (© 2023 Wiley Periodicals LLC.)

Di-(2-ethylhexyl) phthalate (DEHP) might led to chronic and long-term effects on human organs due to its widespread use and bioaccumulation. Despite some cohorts reporting an association between DEHP exposure and BPH, its underlying mechanisms have not been investigated. Our findings indicate that exposure to DEHP or MEHP (main metabolites of DEHP in the human body) leads to increased prostate weights, elevated prostate index, and notable epithelial thickening in rats. It has been observed to promote BPH-1 cell proliferation with effects ranging from low to high concentrations. Transcriptome sequencing analysis of rat prostate tissues identified KIF11 as the key hub gene. KIF11 is highly expressed after DEHP/MEHP exposure, and knocking down of KIF11 inhibits the MEHP-induced promotion of cell proliferation. Exposure to MEHP has been observed to increase the expression of p-GSK-3β and elevate the levels of β-catenin, thereby activating the Wnt/β-catenin signaling pathway. Knocking down of KIF11 significantly inhibits these effects. Histone H3 at Lysine 27 acetylation (H3K27ac) is implicated in the upregulation of KIF11 expression, as evidenced by the addition of the acetylation inhibitor C646. In summary, our findings established that DEHP exposure could promote BPH through H3K27ac regulated KIF11/Wnt/β-catenin signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Diang Dong reports financial support, article publishing charges, and equipment, drugs, or supplies were provided by Science and Technology Department of Sichuan Province., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective/background: Benign prostatic hyperplasia (BPH) is increasing substantial burden on health care systems. Men with high body mass index (BMI) have bigger prostate volumes (PV) with subsequent increase in lower urinary tract symptoms (LUTS) than men with normal BMI. The purpose of this research was to investigate the correlation between Obesity and PV in patients with BPH., Method: The study included 560 patients (50-80 years) with BPH. Weight and height measured to calculate BMI. TRUS was used to measure PV. Patient demographics such as IPSS score and prostate specific antigen (PSA) were also noted., Results: Patients in the study had a mean age of 65.3 ± 9.45 years and the mean BMI was 23.97 ± 4.89 kg/m 2 . The mean PV of each BMI group were 37.45 ± 0.81, 57.89 ± 1.52 and 77.94 ± 2.17 (ml) for normal, overweight and obese groups, respectively, and the average PV score was 57.76 ± 1.50 ml. The mean PSA score was 3.26 ± 0.94 (ng/dl) with a range of 0.6-10.4. There was significant correlation between BMI and PV ( p  = 0.001) as well as between BMI with PSA and IPSS ( p  = 0.02, 0.001, respectively)., Conclusion: The results showing strong correlation between BMI and PV also BMI with PSA and IPSS. Therefore reducing weight may lead to a lower prostate volume in the elderly stage, making LUTS less noticeable and improving quality of life., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Prostate cancer is the second most common cancer in males worldwide, and its incidence is rising. Early detection is crucial for improving the outcomes, but the current screening methods have limitations. While prostate-specific antigen (PSA) testing is the most widely used screening tool, it has poor specificity, leading to a high rate of false positives and unnecessary biopsies. The existing biopsy techniques are invasive and are associated with complications. The liquid biopsy methods that analyze the biomarkers in blood or other bodily fluids offer a non-invasive and more accurate alternative for detecting and characterizing prostate tumors., Methods: Here, we present a novel liquid biopsy method for prostate cancer based on the identification of specific proteins in the extracellular vesicles isolated from the blood of patients with prostate cancer., Results: We observed that a specific combination of sEV proteins is a sensitive indicator of prostate cancer. Indeed, we found that the number of clusters expressed by specific combinations of either intra-vesicular (STAT3 and CyclinD1) or surface proteins (ERBB3, ALK, and CD81) allowed us to significantly discriminate the patients with prostate cancer from the individuals with hyperplasia., Conclusion: This new liquid biopsy method has the potential to improve prostate cancer screening by providing a non-invasive and more accurate diagnostic tool.

Ageratum conyzoides , an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.

Benign Prostatic Hyperplasia (BPH) is a complex condition leading to Lower Urinary Tract Symptoms in aging men, characterized by cellular proliferation, smooth muscle dysfunction, inflammation, and fibrosis. While BPH is known to involve heightened macrophage infiltration, the specific contribution of infiltrating monocytes/macrophages to the disease mechanism remains uncertain. This research explores the impact of reducing circulating monocytes and subsequently limiting their tissue infiltration by using Ccr2 knockout (Ccr2-KO) mice. Ccr2-KO and wild type mice were implanted with testosterone and estradiol (T + E2, 25 mg + 2.5 mg) pellets. Urinary function was assessed via weekly void spot assays over 12 weeks, and prostatic macrophage levels were visualized and quantified in tissue sections using an F4/80 antibody. Additionally, Ki-67 staining was used to evaluate cell proliferation, and picrosirius red staining to assess collagen accumulation. Increased voiding frequency which developed in T + E2 mice, was significantly ameliorated in Ccr2-KO mice, however, both Ccr2-KO and wild type (WT) mice showed increased bladder weights after three month, representing a hypertrophic response to bladder outlet obstruction. T + E2 substantially increased the density of macrophages in WT but not Ccr2-KO mouse prostate. Proliferation rate, as indicated by Ki-67 positivity, was elevated in the vental and anterior prostate lobes but was only marginally reduced in Ccr2-KO mice. Most importantly, a significant prostatic collagen accumulation was observed in WT mice that was markedly reduced by Ccr2 deficiency post T + E2 treatment. The absence of Ccr2 mitigates urinary dysfunction and alters prostatic macrophage levels and collagen accumulation in steroid hormone imbalance. These findings suggest a crucial role for monocyte infiltration, giving rise to macrophages or other cell derivatives, to drive fibrosis., (© 2024. The Author(s).)

Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique., Materials and Methods: Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ., Results: Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001)., Conclusions: The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Steroid 5α reductase 2 (SRD5A2) converts testosterone to dihydrotestosterone and is crucial for prostatic development. 5α reductase inhibitors (5ARI) reduce prostate size in benign prostate hyperplasia (BPH) and ameliorate lower urinary tract symptoms secondary to BPH. However, the mechanisms of 5ARI functioning are still not fully understood. Here, we used a Srd5a2 -/- mouse model and employed single-cell RNA sequencing to explore the impact of SRD5A2 absence on prostate cellular heterogeneity. Significant alterations in luminal epithelial cell (LE) populations were observed, alongside an increased proportion and proliferative phenotype of estrogen receptor 1 (ESR1) + LE2 cells, following an SRD5A2-independent ESR1 differentiation trajectory. LE2 cells exhibited enhanced estrogen response gene signatures, suggesting an alternative pathway for prostate growth when SRD5A2 is absent. Human prostate biopsy analysis revealed an inverse correlation between the expressions of SRD5A2 and LE2 markers (ESR1/PKCα), and an inverse correlation between SRD5A2 and the clinical efficiency of 5ARI. These findings provide insights into 5ARI resistance mechanisms and potential alternative therapies for BPH-related lower urinary tract symptoms. © 2024 The Pathological Society of Great Britain and Ireland., (© 2024 The Pathological Society of Great Britain and Ireland.)

Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine., (© 2024. The Author(s).)

To investigate extracellular vesicles (EVs), biomarkers for predicting lymph node invasion (LNI) in patients with high-risk prostate cancer (HRPCa), plasma, and/or urine samples were prospectively collected from 45 patients with prostate cancer (PCa) and five with benign prostatic hyperplasia (BPH). Small RNA sequencing was performed to identify miRNAs in the EVs. All patients with PCa underwent radical prostatectomy and extended pelvic lymph node dissection. Differentially expressed miRNAs were identified in patients with and without pathologically-verified LNI. The candidate miRNAs were validated in low-risk prostate cancer (LRPCa) and BPH. Four miRNA species (e.g., miR-126-3p) and three miRNA species (e.g., miR-27a-3p) were more abundant in urinary and plasma EVs, respectively, of patients with PCa. None of these miRNA species were shared between urinary and plasma EVs. miR-126-3p was significantly more abundant in patients with HR PCa with LNI than in those without (P = 0.018). miR-126-3p was significantly more abundant in the urinary EVs of patients with HRPCa than in those with LRPCa (P = 0.017) and BPH (P = 0.011). In conclusion, urinary EVs-derived miR-126-3p may serve as a good biomarker for predicting LNI in patients with HRPCa., (© 2024. The Author(s).)

Background: Autophagy is a well-conserved catabolic process that plays a key role in cell homeostasis. In the prostate, defective autophagy has been implicated in the genesis and progression of several pathological conditions., Aim: The present review explored the autophagy pathway in prostate-related dysfunctions, focusing on prostate cancer (PCa), benign prostatic hyperplasia (BPH) and prostatitis., Results: Impaired autophagy activity has been shown in animal models of BPH and prostatitis. Moreover, autophagy activation by specific and non-specific drugs improved both conditions in pre-clinical studies. Conversely, the efficacy of autophagy inducers in PCa remains controversial, depending on intrinsic PCa characteristics and stage of progression. Intriguingly, autophagy inhibitors have shown beneficial effects in PCa suppression or even to overcome chemotherapy resistance. However, there are still open questions regarding the upstream mechanisms by which autophagy is deregulated in the prostate and the exact role of autophagy in PCa. The lack of specificity and increased toxicity associated with the currently autophagy inhibitors limits its use clinically, reflecting in reduced number of clinical data., Conclusion: New therapeutic strategies to treat prostatic diseases involving new autophagy modulators, combination therapy and new drug formulations should be explored. Understanding the autophagy signaling in each prostatic disease is crucial to determine the best pharmacological approach., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). Although LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (eg, prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging; however, its impact on the pathological features of BPH remains unknown., Methods: Publicly available gene array data were analyzed. Immunohistochemistry examined mitochondrial proteins in the human prostate. The effect of complex I inhibition (rotenone) on a prostatic cell line was examined using quantitative polymerase chain reaction, immunocytochemistry, and Seahorse assays. Oleic acid (OA) was tested as a bypass of complex I inhibition. Aged mice were treated with OA to examine its effects on urinary dysfunction. Voiding was assessed longitudinally, and a critical complex I protein measured., Results: Mitochondrial function and fibrosis genes were altered in BPH. Essential mitochondrial proteins (ie, voltage-dependent anion channels 1 and 2, PTEN-induced kinase 1, and NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [NDUFS3]) were significantly (p < .05) decreased in BPH. Complex I inhibition in cultured cells resulted in decreased respiration, altered NDUFS3 expression, increased collagen deposition, and gene expression. OA ameliorated these effects. OA-treated aged mice had significantly (p < .05) improved voiding function and higher prostatic NDUFS3 expression., Conclusions: Complex I dysfunction is a potential contributor to fibrosis and lower urinary tract dysfunction in aged mice. OA partially bypasses complex I inhibition and therefore should be further investigated as a mitochondrial modulator for treatment of LUTS/BPH. Hypotheses generated in this investigation offer a heretofore unexplored cellular target of interest for the management of LUTS/BPH., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: This study aimed to investigate the clinical significance of neutrophil-to-lymphocyte ratio and ultrasonic parameters in diagnosing bladder outlet obstruction in patients with benign prostatic hyperplasia., Material: Between September 2022 and January 2024, a total of 106 patients with benign prostatic hyperplasia were collected from Hongqi Hospital affiliated to Mudanjiang Medical University followed by urodynamic testing. The patients were categorized into three groups based on the International Prostate Symptom Score: mild (45 cases), moderate (36 cases), and severe (25 cases). Thirty-five healthy men were recruited at the hospital as a control group. All patients had blood tests and ultrasound scans., Results: Neutrophil-to-lymphocyte ratio, detrusor wall thickness, detrusor muscle elastic modulus, internal gland elastic modulus, intravesical prostatic protrusion, and post-voiding residual volume were significantly correlated with the bladder outlet obstruction stage and showed good diagnostic efficiency (all P<0.05. There was no statistically significant difference observed in the external gland elastic modulus between the experimental group and the control group (P>0.05)., Conclusions: The neutrophil-to-lymphocyte ratio, detrusor wall thickness, elastic modulus of the detrusor and glandular gland may hold clinical significance for diagnosing bladder outlet obstruction resulting from benign prostatic hyperplasia., (Copyright © 2024. Published by Elsevier Masson SAS.)

Benign prostatic hyperplasia (BPH) is the expansion of the prostate gland that results in urinary symptoms. Both the epithelial-to-mesenchymal transition (EMT) and the Wnt signaling pathway are associated with BPH pathology. In this study, we find that miR-1202 is increased in BPH samples. Overexpression of miR-1202 in TGF-β-treated BPH-1 cells enhances cell survival and DNA synthesis and inhibits cell apoptosis, whereas miR-1202 inhibition partially abolishes the effects of TGF-β on BPH-1 cells. miR-1202 overexpression reduces E-cadherin level but elevates vimentin, N-cadherin, and snail levels, whereas miR-1202 inhibition partially attenuates the effects of TGF-β on EMT markers. Regarding the Wnt/β-catenin pathway, miR-1202 overexpression significantly enhances, whereas miR-1202 inhibition partially decreases, the promotive effects of TGF-β on Wnt1, c-Myc, and cyclin D1 proteins. 3-Hydroxy-3-methylglutaryl-CoA lyase (HMGCL) is a direct downstream target of miR-1202, and miR-1202 inhibits HMGCL expression through binding to its 3'UTR. Overexpression of HMGCL significantly reduces the effect of miR-1202 overexpression on the phenotypes of BPH-1 cells by inhibiting cell survival and promoting apoptosis. Similarly, HMGCL overexpression has the opposite effects on EMT markers and the Wnt/β-catenin signaling, and markedly alleviates the effects of miR-1202 overexpression. Finally, in the BPH rat model, Ki67 and vimentin levels are elevated, but E-cadherin and HMGCL levels are reduced. In conclusion, miR-1202 is upregulated in benign prostatic hyperplasia; miR-1202 enhances epithelial cell proliferation, suppresses cell apoptosis, and promotes EMT by targeting HMGCL. The Wnt/β-catenin pathway may participate in the miR-1202/HMGCL axis-mediated regulation of BPH-1 cell phenotypes.

Background: Given the high prevalence of BPH among elderly men, pinpointing those at elevated risk can aid in early intervention and effective management. This study aimed to explore that polygenic risk score (PRS) is effective in predicting benign prostatic hyperplasia (BPH) incidence, prognosis and risk of operation in Han Chinese., Methods: A retrospective cohort study included 12,474 male participants (6,237 with BPH and 6,237 non-BPH controls) from the Taiwan Precision Medicine Initiative (TPMI). Genotyping was performed using the Affymetrix Genome-Wide TWB 2.0 SNP Array. PRS was calculated using PGS001865, comprising 1,712 single nucleotide polymorphisms. Logistic regression models assessed the association between PRS and BPH incidence, adjusting for age and prostate-specific antigen (PSA) levels. The study also examined the relationship between PSA, prostate volume, and response to 5-α-reductase inhibitor (5ARI) treatment, as well as the association between PRS and the risk of TURP., Results: Individuals in the highest PRS quartile (Q4) had a significantly higher risk of BPH compared to the lowest quartile (Q1) (OR = 1.51, 95% CI = 1.274-1.783, p < 0.0001), after adjusting for PSA level. The Q4 group exhibited larger prostate volumes and a smaller volume reduction after 5ARI treatment. The Q1 group had a lower cumulative TURP probability at 3, 5, and 10 years compared to the Q4 group. PRS Q4 was an independent risk factor for TURP., Conclusions: In this Han Chinese cohort, higher PRS was associated with an increased susceptibility to BPH, larger prostate volumes, poorer response to 5ARI treatment, and a higher risk of TURP. Larger prospective studies with longer follow-up are warranted to further validate these findings., (© 2024. The Author(s).)

Purpose: Benign prostatic hyperplasia (BPH) is one of the most prevalent diseases affecting aging males. However, approximately, 8% of the BPH patients under 50-year-old experience remarkably early progression, for reasons that remain elusive. Among the various factors implicated in promoting BPH advancement, the activation of fibroblasts and autophagy hold particular importance. Our research endeavors to explore the mechanisms behind the accelerated progression in these patients., Methods: Immunohistochemistry and immunofluorescence were performed to detect the expression levels of LC3, p62, PDE5, and α-SMA in diverse BPH tissues and prostate stromal cells. The autophagy activator rapamycin, the autophagy suppressor chloroquine, and siRNA transfection were used to identify the impact of autophagy on fibroblast activation., Results: Prostatic stromal fibroblasts in early progressive BPH tissues displayed activation of autophagy with an upregulation of LC3 and a concurrent downregulation of p62. After starvation or rapamycin treatment to a heightened level of autophagy, fibroblasts exhibited activation. Conversely, chloroquine treatment and ATG-7-knockdown effectively suppressed the level of autophagy and fibroblast activation. High expression of PDE5 was found in early progressive BPH stromal cells. The administration of PDE5 inhibitors (PDE5Is) hindered fibroblast activation through suppressing autophagy by inhibiting the ERK signaling pathway., Conclusion: Our findings suggest that autophagy plays a pivotal role in promoting BPH progression through fibroblast activation, while PDE5Is effectively suppress autophagy and fibroblast activation via the ERK signaling pathway. Nevertheless, further investigations are warranted to comprehensively elucidate the role of autophagy in BPH progression., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Numerous animal models have demonstrated that caloric restriction (CR) is an excellent tool to delay aging and increase the quality of life, likely because it counteracts age-induced oxidative stress and inflammation. The aging process can affect the prostate in three ways: the onset of benign prostatic hyperplasia, prostatitis, and prostate cancer. In this study, we used 14 aged male Sprague Dawley rats, which were allocated into two groups, at the age of 18 months old. One group was fed ad libitum (a normal diet (ND)), and the other group followed a caloric restriction diet with a 60% decrease in intake. The rats were sacrificed at the age of 24 months. By immunohistochemical (IHC) and Western blot (WB) analyses, we studied the variations between the two groups in immune inflammation and fibrosis-related markers in aged prostate tissues. Morphological examinations showed lower levels of prostatic hyperplasia and fibrosis in the CR rats vs. the ND rats. The IHC results revealed that the prostates of the CR rats exhibited a lower immune proinflammatory infiltrate level and a reduced expression of the NLRP3 inflammasome pathway, together with significantly reduced expressions of mesenchymal markers and the profibrotic factor TGFβ1. Finally, by WB analysis, we observed a reduced expression of ERα, which is notoriously implicated in prostate stromal proliferation, and increased expressions of SOD1 and Hsp70, both exerting protective effects against oxidative stress. Overall, these data suggest that CR brings potential benefits to prostatic tissues as it reduces the physiological immune-inflammatory processes and the tissue remodeling caused by aging.

Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor β (TGF-β)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-β/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-β/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH., (© 2024. The Author(s).)

The pathogenesis of benign prostatic hyperplasia (BPH) in dogs is still not fully understood. Some studies suggest that oxidative stress may have a potential role in the pathogenesis of BPH in dogs. Age-related hormonal changes may activate a chronic inflammatory response in the prostate. This causes the generation of reactive oxygen species (ROS) and results in oxidative stress. Excessive production of ROS results in DNA damage and hyperplastic transformation of prostatic cells. The use of antioxidants for improvement of treatment outcomes for canine PBH has been discussed. Further research is needed on the importance of oxidative stress in the development of BPH in dogs and the usefulness of antioxidants in the supportive treatment of this condition., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)