Progression Of Benign Prostatic Hyperplasia Research Articles

Extracellular Vesicles Contribute to Oxidized LDL-Induced Stromal Cell Proliferation in Benign Prostatic Hyperplasia.

Clinical and experimental evidence has linked Benign Prostatic Hyperplasia (BPH) with dyslipidemic and hypercholesterolemic conditions, though the underlying cellular mechanisms remain unclear. This study investigates the impact of dyslipidemia, specifically oxidized LDL (OxLDL), on prostatic stromal cell proliferation and the release of extracellular vesicles (EVs). Mice were fed a high-fat diet, and human prostatic stromal cells (HPSCs) were treated with OxLDL. Proliferation assays and EV characterization were performed to assess the role of EVs in BPH progression. Pro-atherogenic conditions significantly increased cell proliferation in both murine prostatic cells and HPSCs. Treatment with metformin effectively inhibited OxLDL-induced proliferation. Additionally, OxLDL stimulated the production and release of pro-proliferative EVs by HPSCs, which further promoted cellular proliferation. The findings suggest that dyslipidemia drives prostatic stromal cell proliferation and EV secretion, contributing to BPH progression. Metformin demonstrates potential as a therapeutic agent to mitigate these effects, offering insight into novel strategies for BPH management. This study highlights the complex interaction between dyslipidemia, cell proliferation, and extracellular communication in the context of BPH pathogenesis.

The Impact of Covid-19 on Lower Urinary Tract Symptoms (LUTS) in Patients Treated Conservatively for Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a non-malignant urological pathology characterized by a progressive increase in the volume of the prostate gland and one of the important diseases which affect lower urinary tract symptoms (LUTS). Covid-19 is a new viral infection with epidemiological characteristics of a pandemic. The disease is presented as a respiratory, cardiovascular, and neurological late complication. There is limited data that low urinary tract can be affected and aggravate symptoms and quality of life (QoL). Our pilot study describes a male population treated with conservative methods for BPH and the effect of Covid-19 infection on their LUTS and QoL. This was a case-control study between April 2021 and November 2021. The study included 33 patients with a history of Covid-19 infection. The assessment of LUTS was carried out by processing the data obtained from the completed by the patients IPSS questionnaires (the last one before, immediately, and five months after Covid-19). The control group consisted of 50 patients, which for the management of the selection bias, matched according to demographic and clinical features of the group. All patients underwent ultrasound diagnostics giving information about the volume of the prostate gland and the amount of residual urine. Two years after the beginning of the Covid-19 pandemic, we can confidently say that not all characteristics of this type of infection are sufficiently clear. More in-depth studies on Covid-19 as a cause of worsening LUTS and overall progression of BPH could help identify new aspects of infection leading to significant improvements in its treatment.

Predictive Factors for Tissue Inflammation in Patients with Benign Prostatic Hyperplasia: A Clinical Prediction Study

Introduction: Benign prostatic hyperplasia (BPH) is a common condition in older men, marked by the noncancerous enlargement of the prostate gland. Inflammation of the prostate plays a significant role in the progression of BPH and the symptoms it causes. The objective of this study was to create a predictive model for prostatic inflammation in men with BPH based on important clinical factors. Methods: A retrospective cohort study was conducted with 137 patients diagnosed with BPH. Data collected included various factors such as age, prostate volume (PV), preoperative international prostate symptom score, preoperative maximum urine flow rate (Qmax), preoperative post-void residue, weight of the excised tissue, body mass index, fasting blood glucose (FBG), cholesterol levels, prostate-specific antigen, blood calcium, blood phosphorus, blood uric acid, triglycerides, hypertension status, and presence of prostate calcifications. Multivariate logistic regression and LASSO regression analyses were performed to identify significant predictors and develop a nomogram. The model’s performance was evaluated using receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Results: Among the patients, 9.49% showed no signs of prostatic inflammation, while 22.63% had mild, 47.45% had moderate, and 20.44% had severe inflammation. Factors such as PV, FBG, and prostate calcification were identified as important predictors of prostatic inflammation. The predictive model developed exhibited strong discrimination and calibration, as evidenced by a high area under the curve value, indicating reliable predictive accuracy. DCA further validated the clinical usefulness of the nomogram. Conclusion: The developed nomogram, incorporating PV, FBG, and prostate calcification, effectively predicts prostatic inflammation in men with BPH. This tool can aid in early intervention and targeted treatment, potentially improving patient outcomes. Further validation in diverse populations is recommended to enhance its generalizability and clinical applicability.

Ixeris polycephala Extract Alleviates Progression of Benign Prostatic Hyperplasia via Modification of Proliferation, Apoptosis, and Inflammation.

Benign prostatic hyperplasia (BPH) is a urogenital disorder that is common in aging men. Ixeris polycephala (IP) is used in traditional medicine and contains pharmacologically active compounds. However, the effect for BPH progression has not been elucidated. We herein examined the protective potential of IP extract on a testosterone-induced model of BPH in rats. To generate the BPH model, daily subcutaneous administration of testosterone was applied for 4 weeks. During this period, the rats were also administered a daily oral gavage of IP (150 mg/kg), finasteride (positive control), or vehicle. Testosterone treatment was associated with a significantly higher prostate-to-body weight ratio, serum dihydrotestosterone (DHT) level, and prostatic gene expression of 5α-reductase compared to untreated controls. Notably, IP plus testosterone co-treatment was associated with decreased epithelial thickness, down-regulation of proliferating cell nuclear antigen (PCNA) and cyclin D1, and upregulation of pro-apoptotic signaling molecules. IP co-treatment also down-regulated pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and decreased inflammatory cell infiltration compared to the levels seen in the testosterone-induced BPH. IP appears to protect rats against the progression of testosterone-induced BPH by alleviating prostate cell growth and inflammatory responses, and thus may have potential for clinical use against BPH progression.

Combining untargeted and targeted metabolomics to reveal the mechanisms of herb pair Anemarrhena asphodeloides Bunge and Phellodendron chinense C. K. Schneid on benign prostatic hyperplasia

Ethnopharmacological relevanceAnemarrhena 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 studyThis study aimed to clarify potential therapeutic mechanisms of herb pair on BPH from a metabolic perspective. Materials and methodsTestosterone 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. ResultsThe 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. ConclusionsIn 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.

Chronic inflammation in benign prostatic hyperplasia: Pathophysiology and treatment options.

Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.

Evaluation of the Accuracy of the Use of Intravesical Prostatic Protrusion Degree as the Predictor of Benign Prostatic Hyperplasia Management

Managing symptoms of benign prostatic hyperplasia (BPH) is important but preventing the progression of the disease is also necessary. Medical therapy is commonly used to treat BPH as initial therapy. However, not every medical therapy is effective for treating BPH. Intravesical prostatic protrusion (IPP), a manifestation of BPH is used to evaluate BPH progression thus helping clinicians in choosing the effective treatment option. Patients with higher IPP degrees may experience more severe bladder outlet obstruction (BOO). They may not respond well to medical therapies, suggesting that IPP measurement can guide treatment decisions for BPH patients. This study evaluates the accuracy of using IPP degree as a predictor of BPH management by reviewing relevant literature. A comprehensive approach was undertaken, including the selection and filtering of articles from reputable databases and scholarly repositories using specific keywords related to the study's objectives. By measuring IPP degrees, the severity of clinical BPH can be categorized, allowing clinicians to choose effective treatment options and predict treatment outcomes.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Activation of the cGMP/PKG/ERK signaling pathway associated with PDE5Is inhibits fibroblast activation by downregulating autophagy in early progressive benign prostatic hyperplasia.

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. 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. 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. 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.

The Impact of SARS-CoV-2 on Patients With Lower Urinary Tract Symptoms (LUTS).

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the management of patients with lower urinary tract symptoms (LUTS) underwent dynamic adjustments in response to an evolving understanding of the virus's impact on different patient populations. Healthcare practitioners reevaluated therapeutic approaches for conditions like benign prostatic hyperplasia (BPH), considering the potential implications of this condition on the severity and progression of coronavirus disease 2019 (COVID-19). This study aims to investigate potential correlations between SARS-CoV-2 infection severity, exacerbation of LUTS, and BPH progression. This retrospective study includes patients hospitalized in our Urology Department between January 2021 and January 2023, presenting with both SARS-CoV-2 and BPH. Their ages ranged from 57 to 88 years, with a mean age of 65.4 years. The diagnosis of BPH relied on a diagnostic triad consisting of digital rectal examination, biological markers (including prostate-specific antigen (PSA) and free PSA, and ultrasound examination, with both conditions confirmed based on test results. Transurethral resection of the prostate (TURP) procedures utilized monopolar Karl Storz resection equipment, using sorbitol and bipolar Olympus devices for transurethral resection of the prostate in saline (TURPis). Haemostasia was performed using roller balls. Anticoagulation followed a prescribed scheme by cardiologists and infectious disease specialists. Statistical analysis was conducted using IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY: IBM Corp. Among the 138 hospitalized patients affected by both BPH and COVID-19, 18 required emergency endoscopic procedures (specifically TURP or TURPis) to achieve hemostasis (Figures 1, 2). These individuals presented persistent hematuria despite conservative treatments. The mean duration of surgery was 57.9 minutes. Patients who underwent surgery had a longer average hospital stay compared to those who did not, with durations of 10.5 days versus 7.5 days, respectively. Additionally, urethrovesical catheter insertion was necessary in 29 cases due to acute urinary retention or worsening voiding symptoms during hospitalization. These patients are scheduled for further urological evaluation following the resolution of the COVID-19 episode. In a cohort of 53 patients for whom data were accessible, comparisons were made between the pre-COVID status and the levels of the International Prostate Symptom Score (IPSS), post-voiding residue (PVR), and quality of life (QoL). The findings revealed a mean pre-COVID IPSS value of 11.6 and a COVID-related value of 14.2, with a statistically significant difference noted (p < 0.05). The mean pre-COVID PVR was 42.3 cm2, whereas during the COVID-19 period, it measured 62.5 cm2, also exhibiting a significant difference (p < 0.05). Additionally, the QoL showed a mean pre-COVID-19 score of 2.4 and a COVID-19-associated score of 2.9, again demonstrating statistical significance (p < 0.05). The onset of the SARS-CoV-2 pandemic posed novel challenges in the medical realm, impacting the approach to BPH management. A common practice was delaying treatment for chronic BPH until viral infection remission to reduce associated risks. Additionally, our study revealed a worse evolution in LUTS among individuals with severe COVID-19 symptoms.

Integrating spatial transcriptomics and single-cell RNA-sequencing reveals the alterations in epithelial cells during nodular formation in benign prostatic hyperplasia

ObjectiveProliferative nodular formation represents a characteristic pathological feature of benign prostatic hyperplasia (BPH) and serves as the primary cause for prostate volume enlargement and consequent lower urinary tract symptoms (LUTS). Its specific mechanism is largely unknown, although several cellular processes have been reported to be involved in BPH initiation and development and highlighted the crucial role of epithelial cells in proliferative nodular formation. However, the technological limitations hinder the in vivo investigation of BPH patients.MethodsThe robust cell type decomposition (RCTD) method was employed to integrate spatial transcriptomics and single cell RNA sequencing profiles, enabling the elucidation of epithelial cell alterations during nodular formation. Immunofluorescent and immunohistochemical staining was performed for verification.ResultsThe alterations of epithelial cells during the formation of nodules in BPH was observed, and a distinct subgroup of basal epithelial (BE) cells, referred to as BE5, was identified to play a crucial role in driving this progression through the hypoxia-induced epithelial-mesenchymal transition (EMT) signaling pathway. BE5 served as both the initiating cell during nodular formation and the transitional cell during the transformation from luminal epithelial (LE) to BE cells. A distinguishing characteristic of the BE5 cell subgroup in patients with BPH was its heightened hypoxia and upregulated expression of FOS. Histological verification results confirmed a significant association between c-Fos expression and key biological processes such as hypoxia and cell proliferation, as well as the close relationship between hypoxia and EMT in BPH tissues. Furthermore, a strong link between c-Fos expression and the progression of BPH was also been validated. Additionally, notable functional differences were observed in glandular and stromal nodules regarding BE5 cells, with BE5 in glandular nodules exhibiting enhanced capacities for EMT and cell proliferation characterized by club-like cell markers.ConclusionsThis study elucidated the comprehensive landscape of epithelial cells during in vivo nodular formation in patients, thereby offering novel insights into the initiation and progression of BPH.

Effects of Taraxaci Herba (Dandelion) on Testosterone Propionate-Induced Benign Prostatic Hyperplasia in Rats.

Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.

Microbiome analysis reveals the inducing effect of Pseudomonas on prostatic hyperplasia via activating NF-κB signalling

ABSTRACT 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.

Protective Effect of Panicum dichotomiflorum in a Rodent Model of Testosterone-Induced Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a common disease in aging men. Panicum dichotomiflorum (PD) is an annual grass species of Poaceae that is distributed worldwide. The present study examined whether PD has a protective effect against BPH. BPH was generated in rats by daily subcutaneous administration of testosterone for four weeks. During this period, the rats were also given daily oral gavages of an extract of PD (150 mg/kg). After the final treatment, all animals were euthanized and their prostates were collected and weighed. In BPH model rats, the prostate weight and levels of dihydrotestosterone (DHT) and 5α-reductase expression were inhibited following treatment with PD extract. Testosterone-induced increases in prostate gland epithelial thickness and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) were markedly suppressed in PD-treated rats, whereas cleaved caspase-3 levels were increased. PD administration also decreased the expression of transforming growth factor (TGF)-β and vascular endothelial growth factor (VEGF), the phosphorylation of Akt, and inflammatory cytokines levels. Taken together, these results show that PD extract protects against testosterone-induced BPH progression by alleviating prostate cell growth and reducing levels of growth factors and inflammatory cytokines, indicating that PD extract may have potential in protecting against BPH.

Bisphenol A exposure stimulates prostatic fibrosis via exosome-triggered epithelium changes

Fibrosis is the pathological basis for the clinical progression of benign prostatic hyperplasia (BPH). Prostatic fibrosis is an important risk factor in patients with BPH who experience lower urinary tract symptoms. Bisphenol A (BPA) is an environmental endocrine disruptor (EED) that causes prostate defects. The effects of BPA on the prostate were investigated in this study using mouse and human prostate cell models. BPA-induced mouse prostatic fibrosis is characterized by collagen deposition and an increase in hydroxyproline concentration. Furthermore, BPA-exposed prostatic stromal fibroblasts exosomes promote the epithelial-mesenchymal transition of epithelial cells. High-throughput RNA sequencing and functional enrichment analyses show that substantially altered mRNAs, lncRNAs and circRNAs play roles in cellular interactions and the hypoxia-inducible factor-1 signaling pathway. The results showed that exosomes participated in the pro-fibrogenic effects of BPA on the prostate by mediating communication between stromal and epithelial cells and triggering epithelial changes.

Whole-exome sequencing of Nigerian benign prostatic hyperplasia reveals increased alterations in apoptotic pathways.

Through whole-exome sequencing of 60 formalin-fixed paraffin-embedded Nigerian (NGRn) benign prostatic hyperplasia (BPH) samples, we identified germline and somatic alterations in apoptotic pathways impacting BPH development and progression. Prostate enlargement is a common occurrence in male aging; however, this enlargement can lead to lower urinary tract symptoms that negatively impact quality of life. This impact is disproportionately present in men of African ancestry. BPH pathophysiology is poorly understood and studies examining non-European populations are lacking. In this study, NGRn BPH, normal prostate, and prostate cancer (PCa) tumor samples were sequenced and compared to characterize genetic alterations in NGRn BPH. Two hundred and two nonbenign, ClinVar-annotated germline variants were present in NGRn BPH samples. Six genes [BRCA1 (92%), HSD3B1 (85%), TP53 (37%), PMS2 (23%), BARD1 (20%), and BRCA2 (17%)] were altered in at least 10% of samples; however, compared to NGRn normal and tumor, the frequency of alterations in BPH samples showed no significant differences at the gene or variant level. BRCA2_rs11571831 and TP53_rs1042522 germline alterations had a statistically significant co-occurrence interaction in BPH samples. In at least two BPH samples, 173 genes harbored somatic variants known to be clinically actionable. Three genes (COL18A1, KIF16B, and LRP1) showed a statistically significant (p < 0.05) higher frequency in BPH. NGRn BPH also had five gene pairs (PKD1/KIAA0100, PKHD1/PKD1, DNAH9/LRP1B, NWD1/DCHS2, and TCERG1/LMTK2) with statistically significant co-occurring interactions. Two hundred and seventy-nine genes contained novel somatic variants in NGRn BPH. Three genes (CABP1, FKBP1C, and RP11-595B24.2) had a statistically significant (p < 0.05) higher alteration frequency in NGRn BPH and three were significantly higher in NGRn tumor (CACNA1A, DMKN, and CACNA2D2). Pairwise Fisher's exact tests showed 14 gene pairs with statistically significant (p < 0.05) interactions and four interactions approaching significance (p < 0.10). Mutational patterns in NGRn BPH were similar to COSMIC (Catalog of Somatic Mutations in Cancer) signatures associated with aging and dysfunctional DNA damage repair. NGRn BPH contained significant germline alteration interactions (BRCA2_rs11571831 and TP53_rs1042522) and increased somatic alteration frequencies (LMTK2, LRP1, COL18A1, CABP1, and FKBP1C) that impact apoptosis. Normal prostate development is maintained by balancing apoptotic and proliferative activity. Dysfunction in either mechanism can lead to abnormal prostate growth. This work is the first to examine genomic sequencing in NGRn BPH and provides data that fill known gaps in the understanding BPH and how it impacts men of African ancestry.

Untargeted metabolomics reveals that declined PE and PC in obesity may be associated with prostate hyperplasia.

Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood. A prospective case-control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF). A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms. In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

YAP1 Recognizes Inflammatory and Mechanical Cues to Exacerbate Benign Prostatic Hyperplasia via Promoting Cell Survival and Fibrosis.

Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated whether yes-associated protein 1 (YAP1), an organ size controller and mechanical transductor, is implicated in inflammation-induced BPH. The correlation between YAP1 expression and fibrosis in human and rat BPH specimens is analyzed. Furthermore, the effects of YAP1 activation on prostatic cell survival and fibrosis, as well as the underlying mechanism, are also studied. As a result, total and nuclear YAP1 expression, along with downstream genes are significantly upregulated in inflammation-associated human and rat specimens. There is a significant positive correlation between YAP1 expression and the severity of fibrosis or clinical performance. YAP1 silencing suppresses cell survival by decreasing cell proliferation and increasing apoptosis, and alleviates fibrosis by reversing epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in prostatic BPH-1 and WPMY-1 cells. Mechanistically, inflammatory stimulus and rigid matrix stiffness synergistically activate the RhoA/ROCK1 pathway to provoke cytoskeleton remodeling, thereby promoting YAP1 activation to exacerbate BPH development. Overall, inflammation-triggered mechanical stiffness reinforcement activates the RhoA/ROCK1/F-actin/YAP1 axis, thereby promoting prostatic cell survival and fibrosis to accelerate BPH progression.

Possible therapeutic role of zinc oxide nanoparticles versus vanillic acid in testosterone-induced benign prostatic hyperplasia in adult albino rat: A histological, immunohistochemical and biochemical study

BackgroundThe search for alternative therapies for treatment of Benign prostatic hyperplasia (BPH) has been increasingly studied to avoid the common adverse effects of the usual regimens. Therefore, this study aimed at delineating possible mechanisms of benign prostatic hyperplasia (BPH) and possible therapeutic role of zinc oxide nanoparticles (ZnO-NPs) versus vanillic acid. MethodsForty rats were divided into five groups: control, sham control, Testosterone-induced BPH, BPH and Zn-NPs, and BPH and vanillic acid. Light microscopic, immune-histochemical; PCNA, Bcl-2, Bax, caspase-3, p-Akt and p-mTOR, histomorphometric analysis, MDA/SOD and GPx and were done. Gene expression of p-Akt, p-mTOR and survivin were evaluated. ResultsApplication of zinc oxide nanoparticles as well as vanillic acid significantly reduced prostatic index, epithelial thickness, stromal collagen fibers, expression of PCNA, Bcl2, p-Akt, p-mTOR and MDA tissue level (p < 0.05). Whereas expression of Bax and caspase 3, and tissue levels of SOD and GPx were significantly increased in groups treated with Zno-Nps and vanillic acid compared to that of BPH group. Zinc oxide nanoparticles showed a better effect than vanillic acid in alleviating BPH. ConclusionThese findings suggested that ZnO-NPs as well as VA ameliorated the histolo-pathological and biochemical effects of induced BPH, moreover they improved the proapoptotic and antioxidant parameters which ere induced in BPH. It is recommended to search for new agents to prevent the development and progression of BPH.

Canagliflozin alleviates experimentally induced benign prostate hyperplasia in a rat model: exploring potential mechanisms involving mir-128b/EGFR/EGF and JAK2/STAT3 signaling pathways through in silico and in vivo investigations

Benign prostatic hyperplasia (BPH) poses a significant health concern amongst elderly males. Canagliflozin (Cana), a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, has a powerful anti-inflammatory influence. Nevertheless, its role in treating BPH has not been clarified. Therefore, the study aimed to investigate the potential ameliorative effect of Cana on experimentally induced BPH in rats and explore the underlying mechanisms compared to the standard finasteride (Fin). The study employed histological analysis, biochemical assays using ELISA, and western blotting. Animals were categorized into four groups: Control (2.5 ml/kg CMC, orally + 3 ml/kg olive oil, subcutaneous), BPH (3 mg/kg testosterone, subcutaneous + CMC orally), Fin-treated BPH (5 mg/kg, orally), and Cana-treated BPH (5 mg/kg, orally), for 28 days. The BPH group showed obvious BPH manifestations including an increase in prostate weight (PW), prostate index (PI), dihydrotestosterone (DHT) level, and histological aberrations compared to control. Fin and Cana therapy had a comparable impact. Cana treatment significantly reduced PW and PI, besides it improved prostatic biochemical, and histopathological features compared to BPH, consistent with in silico study findings. Cana was associated with downregulation of the androgen axis, increased miR-128b expression, with a lowered expression of epidermal growth factor (EGF) and its receptor. Phosphorylation of STAT3 and its downstream proliferative markers were significantly reduced suggesting apoptotic activity. Cana markedly rescued the BPH-induced upregulation of IL-1β, and iNOS levels. Altogether, the current study demonstrates that Cana could impede BPH progression, possibly by modulating miR-128b/EGFR/EGF and JAK2/STAT3 pathways and downregulating AR, cyclin D1, and PCNA immunoreactivity.