Reduction In Prostate Size Research Articles

Hosta plantaginea (Lam.) Aschers flower modulates inflammation and amino acid metabolism by inhibiting NF-κB/MAPK/JAK-STAT/PI3K-Akt and AMPK pathways to alleviate benign prostatic hyperplasia in rats

Benign prostatic hyperplasia (BPH) is the most common urogenital disease in men with no definitive treatment. Inflammation, androgen imbalance, and oxidative stress play crucial roles in the pathogenesis of BPH. The flower of Hosta plantaginea (Lam.) Ascher is a pivotal medicinal plant in China, used to treat BPH. However, its effect and mechanism against BPH have not been clear. Our aim was to decipher the pharmacodynamics and mechanisms of H. plantaginea flower against BPH. The extract yields and HPLC-based chemoprofile of ethanolic extract (HP) and total flavonoid (TF) of H. plantaginea flowers were used as reference standard to ensure their quality. The testosterone propionate-induced BPH rat model was used to assess the effects of HP and TF. Protein expression, metabolomics, and network pharmacology analyses were performed. Twenty constituents were identified in both HP and TF, with four quantitatively analyzed using the HPLC method. HP and TF demonstrated significant therapeutic effects on BPH, including reduced prostate size and prostatic index, improved pathological injury of prostate, as well as increased levels of testosterone, superoxide dismutase, glutathione, and glutathione peroxidase, along with decreased levels of dihydrotestosterone, 5 alpha-reductase, epidermal growth factor, TNF-α, IL-1β, IL-6, and malondialdehyde. Western blotting assay indicated that HP and TF prominently inhibited the protein expression of phosphorylated p65, IκBα, JNK, p38, Erk1/2, JAK1, STAT3, PI3K, Akt, and AMPKα1 in a dose-dependent manner. Integrating metabolomics and network pharmacology analyses revealed that HP and TF observably regulated 30 differential metabolites and 11 hub genes across the aforementioned pathways, which are closely associated with amino acid metabolism. The proposed comprehensive strategy of in vivo experiments, metabolomics, and network pharmacology studies has demonstrated that HP and TF could alleviate BPH injury in rats by suppressing inflammation, androgen imbalance, oxidative stress, and amino acid metabolism through the inhibition of NF-κB, MAPK, JAK-STAT, PI3K-Akt, and AMPK pathways, which provides novel insights into the potential of H. plantaginea flower as a treatment for BPH.

Characterizing prostate zonal shape changes associated with 5α-reductase inhibitors using MRI.

Benign prostatic hyperplasia (BPH) is a prevalent medical disorder that primarily affects elderly males. It is distinguished by enhanced angiogenesis of the prostate, aggravating lower urinary tract symptoms (LUTS) and diminishing overall quality of life. Dutasteride, a 5α-reductase inhibitor, has emerged as a significant therapeutic choice for BPH owing to its efficacy in reducing prostate volume. The objective of this study is to analyze alterations in the shapes of prostate zones resulting from dutasteride treatment of BPH, using MRI. We examined 19 drug-administered patients and 33 non-drug-administered patients. MRI sections of all participants before and after drug treatment were collected retrospectively. The transition zone and peripheral zone of the prostate were marked with selected landmarks using TPSDIG v2.04. Generalized Procrustes Analysis was used to analyze shapes statistically. Our results showed that the 5α-reductase inhibitor significantly altered the shape of the transition zone by narrowing its posterior part. There were significant statistical differences between the drug-administered and non-drug-administered groups in the initial and final shapes of the transition zone. These findings indicate that the use of 5α-reductase inhibitors yielded favorable outcomes in terms of prostate size reduction and amelioration of symptoms associated with BPH.

Androgen receptor deficiency-induced TUG1 in suppressing ferroptosis to promote benign prostatic hyperplasia through the miR-188-3p/GPX4 signal pathway

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.

The Role of Surgical Androgen Deprivation in the Treatment of Patients With Urine Retention Due to Prostate Cancer

Background: Surgical androgen deprivation (SAD) and temporary urethral catheterization remain the most suitable therapy for locally advanced prostate cancer (PC). This study aimed to assess the suitable interval duration for voiding trial without a catheter (TWOC) after SAD and to correlate the Gleason score, prostate volume, and PSA level with the free-catheter voiding success. Methods: A total of 62 patients with urine retention due to PC were included in this study. PSA, pelvic ultrasound, and Gleason score were done prior to SAD as baseline measurements and repeated four weeks after surgery. Initial two-week voiding TWOC was done for all patients and repeated after two weeks for patients who failed the initial voiding TWOC. Results: The results showed that 34 (54.8%) patients had Gleason score >7, 21 (33.9%) had a score of 7, and 7 (11.3%) had a score <7. Following SAD, the mean prostate size reduction was seen in 36 (58%) patients, whereas PSA ranged between 0.87 and 38 ng/ml with a mean reduction level of 10.9 ng/ml. All patients with Gleason ≤7 could void free one month after SAD. Five patients with Gleason >7 failed to void free and needed TURP tunneling. In summary, 39 (62%) were void-free after two weeks, 18 (29%) after one month, and the remaining 5 (8.1) required tunneling TURP. Conclusion: The initial TWOC should start two weeks after SAD and followed by a second voiding TWOC two weeks later. Those who fail the second voiding TWOC usually have high Gleason scores, and tunneling TURP may be the best option to treat such patients.

Prostate size, source configuration, and dosimetry dynamics of stranded 125I seed implants

PURPOSETo quantify changes in prostate size and seed movement over time after transperineal implantation of stranded 125I seeds, and to determine their impact on prostate dosimetry. METHODSCT and MR (T2, balanced steady-state free precession) image triplets were acquired on days 0, 3, 10, and 30 for a cohort of 20 patients and registered automatically. Prostate contours were drawn on MR-T2 images; seeds were found and matched in successive CT images. Prostate volume and dimensions, seed movements, and prostate dose metrics V200, V150, V100 and D90 were calculated, and their dynamic behaviors quantified in an operationally defined prostate coordinate system. RESULTSCohort-averaged reductions in prostate A-P dimension (∼8%) and L-R dimension (∼5%) inferred from seed movements agreed with those obtained from contour measurements, whereas prostate volume and S-I dimension (implant direction) reductions inferred from seed movements were overestimated by about 30%. Average overall seed movement was 4.8 ± 3.0 mm, of which the only identifiable systematic component was resolution of prostate edema. Cohort-averaged ratios of prostate V200, V150, V100, and D90 on day 30 relative to day 0 were 1.67, 1.33, 1.02, and 1.08, respectively. CONCLUSIONSPostimplant prostate size reduction in the SI (implant) direction cannot reliably be inferred from stranded seed movements. Apart from large-scale migration, residual seed movements relative to the prostate after accounting for edema resolution appear to be random. Prostate V100 and D90 changes 30 days post implant are modest, whereas those for V150 and V200 are substantial.

Comparative Effects of Ripe and Unripe Lime (Citrus aurantifolia) on Spermatozoa and Gonadosomatic Index in Matured Male Wistar Rats

To ascertain the comparative effects of ripe and unripe Lime (Citrus aurantifolia) on spermatozoa and gonadosomatic index evaluation in matured male Wistar rats; exploring the idea that both ripe and unripe Lime (Citrus aurantifolia) might or might not positively affect semen quality, crucial for male fertility. Twenty-eight (28) sexually mature male Wister rats, aged 9–10 weeks and weighing between 211.50g and 217.00g, were divided equally into seven groups (1 to 7); with Group 1 serving as the control and Groups 2 to 7 receiving 25%, 50%, and 75% concentrations of ripe lime juice (RLJ) and unripe lime juice (ULJ) respectively. The findings indicated that ULJ had a higher concentration (0.1mg/ml) compared to ripe lime RLJ at 0.08mg/ml, although both had approximately the same LD50 value of 1581.138mg/kg. RLJ, at different concentrations, adversely impacted the reproductive performance of rats, leading to decreased progressive motility, livability, sperm count, testicular size, and sexual drive. However, ULJ did not exhibit these effects. A 75% concentration of RLJ showed anti-prostatic activity, causing a reduction in prostate size, which was more pronounced than that of the same ULJ concentration. Importantly, both RLJ and ULJ did not have a significant impact on the sizes of the liver, spleen, heart, kidneys, and lungs, with these visceral organs maintaining normal sizes comparable to the control group (statistically, p>0.05).The findings suggest that RLJ or ULJ consumption, particularly at the highest concentration, may lead to alterations in reproductive performance, hence such consumption should be discouraged.

Transurethral water vapour therapy (Rezūm) for catheter‐dependent men secondary to benign prostatic hyperplasia: A retrospective study in a Hong Kong population

AbstractAimRezūm is a novel treatment for patients with moderate to severe lower urinary tract symptoms as a result of benign prostatic hyperplasia (BPH). Recently, it has expanded to patients with urinary retention causing catheter dependence and the results are promising in Whites. However, it is unclear how effective Rezūm is in the Chinese population. Here, we report our experience in performing Rezūm on catheter‐dependent Chinese men with BPH and evaluate its safety and efficacy.MethodsA retrospective review of catheter‐dependent patients with BPH who underwent Rezūm from January to August 2022 was conducted. We evaluated the success rate of trial without catheter (TWOC) and compared pre‐ and post‐operative (at 6 months) uroflowmetry results, International Prostate Symptoms Score (IPSS), IPSS Quality of Life Score (IPSS QoL), and prostate volume.ResultsSixty‐three patients had Rezūm performed (44 and 19 patients had refractory urinary retention and obstructive uropathy, respectively) with a mean age of 74 years and a mean prostate size of 53.9 mL. The first attempt at TWOC was successful in 53 patients (85.5%; range 15–44 days post‐operation). By 98 days after the operation, all patients could void spontaneously. The 6‐month follow‐up showed that IPSS and IPSS QoL scores decreased by a mean of 9.0 and 1.8 points, respectively (both P < .01). The mean pre‐operative post‐voided residual urine was reduced by 559 mL (P < .01), with a mean prostate size reduction of 9.4 mL (P < .01). Seven patients had non‐serious complications (Grade 1–2 Clavien–Dindo classification) within 30 days of operation.ConclusionRezūm was shown to be effective and safe in catheter‐dependent Chinese men with BPH.

Enhanced prostatic Esr1+ luminal epithelial cells in the absence of SRD5A2.

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.

Effect of dose reduction of dutasteride in combination with alpha-blockers in patients with lower urinary tract symptoms/benign prostatic enlargement.

Dutasteride is used in the treatment of benign prostate enlargement with reported many side effects. The purpose of this study is to examine how different doses of dutasteride (0.5 mg) in combination with tamsulosin affect the outcome of treatment of benign prostatic enlargement (BPE). Prospective study (phase III trial). Between April 2017 and March 2020, this randomized study was conducted on 300 patients with moderate-to-severe lower urinary tract symptoms attributable to BPE and a prostate volume of more than 40 cc. The patients were divided into three therapy groups at random (one-to-one randomization), each with 100 patients: (Group I) daily tamsulosin 0.4 mg plus dutasteride (0.5 mg). (Group II) every other day tamsulosin 0.4 mg plus dutasteride 0.5 mg. (Group III) once a week tamsulosin 0.4 mg plus dutasteride 0.5 mg. Statistical analysis was carried out with the help of the SPSS program 22. (IBM, Armonk, NY, USA). The mean and standard deviation (SD) are used to express quantitative data (SD). When comparing two means, an independent-samples t-test of significance was used. To compare more than two means, a one-way analysis of variance was utilized. For multiple comparisons between distinct variables, a post hoc test was performed. Patients were followed up every 3 months, with a 1-year follow-up to examine the medications' efficacy, prostate size reduction, and erectile function. After 1 year of treatment, all groups showed significant improvement in their symptom scores. However, Groups I and II experienced a considerable reduction in prostate size after therapy, but Group III experienced no meaningful reduction. In terms of sexual dysfunction, there was a considerable shift in Group I after 12 months. Dutasteride treatment on the other day schedule has the same efficacy as the daily dose on prostate size at the same time; the other day scheduled dose has better preservation of sexual function.

Effects of a proprietary mixture of extracts from Sabal serrulata fruits and Urtica dioica roots (WS®1541) on prostate hyperplasia and inflammation in rats and human cells.

Introduction: Phytotherapeutics, particularly extracts from Sabal serrulata (saw palmetto) fruit or Urtica dioica (stinging nettle) root, are popular for the treatment of male lower urinary symptoms in many countries, but their mechanism of action is poorly understood. We performed in vivo and in vitro studies to obtain deeper insight into the mechanism of action of WS®1541, a proprietary combination of a Sabal serrulata fruit and an Urtica dioica root extract (WS® 1473 and WS®1031, respectively) and its components. Methods: We used the sulpiride model of benign prostatic hyperplasia in rats and tested three doses of WS®1541 in comparison to finasteride, evaluating weight of prostate and its individual lobes as well as aspects of inflammation, oxidative stress, growth and hyperplasia. In human BPH-1 cells, we studied the effect of WS®1473, WS®1031, WS®1541 and finasteride on apoptosis, cell cycle progression and migrative capacity of the cells. Results: WS®1541 did not reduce prostate size in sulpiride treated rats but attenuated the sulpiride-induced changes in expression of most analyzed genes and of oxidized proteins and abrogated the epithelial thickening. In vitro, WS®1473 and WS®1031 showed distinct profiles of favorable effects in BPH-1 cells including anti-oxidative, anti-proliferative and pro-apoptotic effects, as well as inhibiting epithelial-mesenchymal-transition. Conclusion: This data supports a beneficial effect of the clinically used WS®1541 for the treatment of lower urinary tract symptoms associated with mild to moderate benign prostate syndrome and provides a scientific rationale for the combination of its components WS®1473 and WS®1031.

Efficacy of Prostatic Artery Embolization in Symptomatic Benign Enlargement of Prostate (>100 cc): A Hospital-based Prospective Study in a Tertiary Care Center

Abstract Background: Prostatic artery embolization (PAE) has recently emerged as an effective minimally invasive procedure for the treatment of patients with symptomatic benign enlargement of prostate (BEP). Aim and Objective: The objective of the study was to evaluate the efficacy of PAE in BEP patients. Materials and Methods: A prospective observational clinical study was conducted at tertiary care hospital over 1-year from April 2022 to March 2023. This study included patients with lower urinary tract symptoms indicative of BEP and a prostate volume of 100 cc or more. The primary endpoints of the study were determining the International Prostate Symptom Score (IPSS), Q-max, prostate volume, intraprostatic resistive index, and prostate-specific antigen (PSA). Results: A total of 21 patients, with a mean age of 72 years were included in the study. After a 6-month follow-up, 15 patients were catheter-free, while 6 patients required adjunctive surgical treatment in the form of transurethral resection of prostate or holmium enucleation of prostate. The mean IPSS significantly decreased from 22 to 8 after PAE (P = 0.0394 Mean Q-max significantly increased from 8 mL/s to 16 mL/s (P = 0.05), while prostate volume decreased significantly at 6 months’ follow-up (122.0 cc vs. 58.0 cc, P = 0.0334). Intraprostatic resistive index showed a statistically significant increase after embolization of unilateral/bilateral prostatic arteries. 0.62 versus 1.34, P = 0.0317, and serum PSA values were comparable pre- and post- PAE. Conclusion: PAE effectively treats symptomatic BEP with a prostatic volume of 100cc or more, achieving a success rate of 71.5% with improvements in IPSS, increased Q-max values, and reduced prostate size.

Prostatic Artery Embolization (PAE)

Benign prostatic hyperplasia (BPH) is a common condition affecting the majority of men over 60 years of age. BPH incidence increases with age and often leads to lower urinary tract symptoms including frequency, urgency, and straining. In patients that do not respond to pharmacological therapy, options include transurethral procedures such as transurethral resection (TURP) or photovaporization, surgical prostatectomy and prostate artery embolization (PAE). The goal of PAE is to occlude arterial supply to the prostate by selective catheterization and subsequent embolization, most commonly with spherical tris-acryl gelatin microspheres. Over weeks to months, reduced blood flow leads to necrosis of prostatic adenomatous tissue, resulting in reduction of prostate size and decreased urethral impingement, eventually allowing for long-term resolution of symptoms in a majority of patients. Advantages of this technique compared with the standard surgical option, TURP, include faster recovery times, fewer side effects, and lower complication rates with near equal efficacy.

5-alpha reductase inhibitors and MRI prostates: actively reducing prostate sizes and ambiguity

BackgroundMagnetic resonance imaging (MRI) scans are increasingly first-line investigations for suspected prostate cancer, and essential in the decision for biopsy. 5-alpha reductase inhibitor (5-ARI) use has been shown to reduce prostate size and prostate cancer risk. However, insufficient data exists on how 5-ARI use affects MRI findings and yield of biopsy. This study explores the differences in imaging and prostate cancer diagnoses between patients receiving and not receiving 5-ARI therapy.MethodsFrom 2015 to 2020, we collected retrospective data of consecutive patients undergoing prostate biopsy at one centre. We included patients who were biopsy-naïve, had prior negative biopsies, or on active surveillance for low-grade prostate cancer. Clinical and pathological data was collected, including 5-ARI use, Prostate Imaging Reporting and Data System (PIRADS) classification and biopsy results.Results351 men underwent saturation biopsy with or without targeted biopsies. 54 (15.3%) had a history of 5-ARI use. On mpMRI, there was no significant difference between the 5ARI and non-5-ARI groups in PIRADS distribution, number of lesions, and lesion location. Significantly fewer cancers were detected in the 5-ARI group (46.3% vs. 68.0%; p < 0.01). There were no significant differences in PIRADS distribution in 5-ARI patients with positive and negative biopsy.ConclusionOur study found significant differences in biochemical, imaging and biopsy characteristics between 5-ARI and non-5-ARI groups. While both groups had similar PIRADS distribution, 5-ARI patients had a lower rate of positive biopsies across all PIRADS categories, which may suggest that the use of 5ARI may confound MRI findings. Further studies on how 5-ARI therapy affects the imaging characteristics of prostate cancer should be performed.

PD02-08 ESR1+ LUMINAL EPITHELIAL CELLS DRIVE THE PROSTATE GROWTH AND SURVIVAL IN THE ABSENCE OF SRD5A2

You have accessJournal of UrologyCME1 Apr 2023PD02-08 ESR1+ LUMINAL EPITHELIAL CELLS DRIVE THE PROSTATE GROWTH AND SURVIVAL IN THE ABSENCE OF SRD5A2 Christina Sharkey, Xingbo Long, Ra'ad Al-Faouri, Aria F. Olumi, and Zongwei Wang Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Aria F. OlumiAria F. Olumi More articles by this author , and Zongwei WangZongwei Wang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. 5α reductase inhibitors (5ARI) are the only class of benign prostate hyperplasia-related medications that reduce prostate size. However, why the patients respond variably to 5ARI therapies is still largely unknown. We previously demonstrated that 30% of adult human prostatic tissues do not express the SRD5A2 gene and protein via epigenetic modifications. We established a SRD5A2 null (Srd5a2-/-) mouse model and through single cell RNA sequencing, we identified LE2, a sub-cell population of ESR1+ luminal epithelial that is upregulated in Srd5a2-/- mice. Our goal in this study is to characterize the spatial expression of LE2 markers and its functional phenotype when SRD5A2 is absent. METHODS: Homozygous Srd5a2-/- mice and littermate control heterozygous SRD5A2+/- mice were generated and differentially expressed gene profiles of LE2 were obtained from single-cell RNA sequencing (scRNA seq). Spatial expression of LE2 markers was evaluated by RNA fluorescence in-situ hybridization (RNA-FISH). Cell proliferation was detected by Ki67 and BrdU staining. The Cell Death and ER signaling pathways were evaluated with RT2 PCR profiler arrays (84 genes per array) and downstream signaling pathways were analyzed by western blot. Prostate biopsies from the clinical trial of 5ARI for Medical Therapy of Prostatic Symptoms (MTOPS) were used for immunohistochemistry. RESULTS: The prostate weight of Srd5a2-/- mice was significantly decreased compared to Srd5a2+/- littermate control mice (p<0.001). The prostate cell proliferation was suppressed in Srd5a2-/- mice (p=0.05). The cell death signaling akt1, caspase 7, caspase 9, and ER target genes cyp1a1 and vegfa were downregulated (p<0.05). On the other hand, in the anterior lobe of prostate of Srd5a2-/- mice, the cell proliferation was higher than that in control. scRNA seq showed that ESR1 was expressed mainly in the prostate anterior lobe and the number of ESR1+ LE2 cells was significantly increased upon SRD5A2 absence. This was confirmed by RNA-FISH using the probes of LE2 cell markers ESR1 and PVT1. Co-staining of LE2 cell markers ESR1 and PKCa in prostate biopsies of MTOPS further confirmed the existence of an equivalent LE2 cell population in the human prostate with BPH. CONCLUSIONS: Our data demonstrate that LE2, the subpopulation of prostate cells may play an important role in alternative pathways for prostate growth and survival in absence of SRD5A2 and androgen deprivation. Understanding the underlying androgen-independent pathways contributing to prostate growth can help identify novel therapeutic targets for the management of prostatic diseases. Source of Funding: NIH/R01 DK124502 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e71 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Ra'ad Al-Faouri More articles by this author Aria F. Olumi More articles by this author Zongwei Wang More articles by this author Expand All Advertisement PDF downloadLoading ...

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Commentary on "Integrative multiplatform molecular profiling of benign prostatic hyperplasia identifies distinct subtypes".

Benign prostatic hyperplasia treated with individualised homoeopathic medicines: An evidence-based case series

The study aimed to evaluate the effects of homoeopathic treatment in patients with benign prostatic Hypertrophy (BPH). This was an experimental study conducted using the primary data and assessed based on clinical symptoms and pathological reports. A total of three cases were included in this study. BPH was diagnosed based on clinical symptoms and ultrasonography reports. The patients were prescribed Lycopodium clavatum, Thuja occidentalis and Arsenicum album based on clinical signs, the totality of symptoms and individualisation. Dietary changes were recommended as well. Improvement was assessed based on symptom reduction and changes in ultrasonography reports. All three patients improved clinically and pathologically, including a reduction in prostate size. This case series provides evidence that individualised homoeopathic treatment is effective in pathological conditions such as BPH, in both symptom relief and pathological changes.

Ameliorative Effect of Structurally Divergent Oleanane Triterpenoid, 3-Epifriedelinol from Ipomoea batatas against BPA-Induced Gonadotoxicity by Targeting PARP and NF-κB Signaling in Rats.

The pentacyclic triterpenoids (PTs) of plant origin are reputed to restrain prostate cancer (PCa) cell proliferation. This study aims to assess 3-epifriedelinol (EFD) isolated from aerial part of Ipomoea batatas against PCa and its potential mechanism, in vitro and in vivo. Molecular docking affirms good binding affinity of the compound with target proteins exhibiting binding energy of -7.9 Kcal/mol with BAX, -8.1 Kcal/mol (BCL-2), -1.9 Kcal/mol (NF-κB) and -8.5 Kcal/mol with P53. In the MTT assay, EFD treatment (3-50 µM) showed a significant (p &lt; 0.05 and p &lt; 0.01) dose and time dependent drop in the proliferative graph of DU145 and PC3, and an upsurge in apoptotic cell population. EFD displayed substantial IC50 against DU145 (32.32 ± 3.72 µM) and PC3 (35.22 ± 3.47 µM). According to Western blots, EFD administration significantly enhanced the cleavage of caspases and PARP, elevated BAX and P53 and decreased BCL-2 and NF-κB expression, thereby triggering apoptosis in PCa cells. When male Sprague Dawley rats were intoxicated with Bisphenol A (BPA), an apparent increase in prostate mass (0.478 ± 0.08 g) in comparison to control (0.385 ± 0.03 g) indicates prostatitis. Multidose treatment of EFD (10 mg/kg) significantly reduced prostate size (0.404 ± 0.05 g). EFD exhibited substantial curative potential in vivo, as hematological, hormonal and histopathological parameters have been significantly improved. Reduced peroxidation (TBARS), and suppression of inflammatory markers i.e., NO, IL-6 and TNF-α, signposts substantial antiinflammatory potential of the compound. Overall, EFD has shown better binding affinity with target molecules, acceptable ADMET profile, potent antiproliferative and apoptotic nature and significant reduction in inflamed prostate mass of rats. The present study demonstrates acceptable physicochemical and pharmacokinetic properties of the compound with excellent drugable nature, hence EFD in the form of standardized formulation can be developed as primary or adjuvant therapy against PCa and toxins-induced gonadotoxicity.

A Combination of Natural Products, BenPros (Green Tea Extract, Soybean Extract and Camellia Japonica Oil), Ameliorates Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men and causes lower urinary tract symptoms due to excessive proliferation of prostate stromal and epithelial cells. The present study investigated the improving effect of BenPros, an edible natural product mixture (green tea extract, soybean extract and camellia japonica oil), against the development of BPH in vitro and in vivo. BenPros treatment showed inhibitory ability on testosterone-induced androgen receptor, prostate-specific antigen (PSA), and 5α-reductase protein expression in LNCap-LN3 cells and anti-inflammatory effects on LPS-induced increases in interleukin-6 and tumor necrosis factor-α in RAW264.7 cells. In a testosterone propionate (TP)-induced BPH rat model, BenPros decreased the up-regulated serum 5α-dihydrotestosterone and PSA levels. Moreover, BenPros also significantly reduced PSA protein expression in prostate tissue. Furthermore, TP-induced increased expression of cyclooxygenase 2 and B-cell lymphoma 2 (Bcl-2) were reduced by BenPros, resulting in an increase in the Bcl-2/BCL2-related X ratio. These regulatory abilities of BenPros on BPH inducing markers also reduced prostate size and epithelial thickness based on histological analysis. These results indicate that BenPros has a protective ability against BPH in vitro and in vivo, and it may be a promising candidate as a functional food in regulating BPH.

PD16-08 ALTERNATE ANDROGEN-INDEPENDENT ESTROGEN SIGNALING FOR PROSTATIC GROWTH

You have accessJournal of UrologyCME1 May 2022PD16-08 ALTERNATE ANDROGEN-INDEPENDENT ESTROGEN SIGNALING FOR PROSTATIC GROWTH Christina Sharkey, Xingbo Long, Ra'ad Al-Faouri, Zongwei Wang, and Aria F. Olumi Christina SharkeyChristina Sharkey More articles by this author , Xingbo LongXingbo Long More articles by this author , Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002548.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Steroid 5α reductase 2 (SRD5A2) is the predominant enzyme responsible for prostatic development and growth. SRD5A2 inhibitors (5ARI) are the only class of benign prostate hyperplasia-related medications that reduce prostate size. However, the progression of lower urinary tract symptoms (LUTS) associated with BPH was only slowed by 34% in those treated with 5ARI. Through epigenetic regulation, we have shown that one-third of adult patients lack expression of prostatic SRD5A2. Here we wished to identify the subpopulation of prostate cells resistant to 5ARI therapy and determine alternative non-androgenic pathways that contribute to prostate growth in the absence of SRD5A2. METHODS: Single prostatic cells of homozygous SRD5A2-/- mice and littermate heterozygous SRD5A2+/- control mice were isolated and processed using the 10x genomics platform for single cell RNA-sequencing (scRNA-seq). A complete transcriptomic profile was obtained to identify cellular subsets and functional differentiation. Specific cell clusters were validated in situ using immunohistochemistry and RNA in situ hybridization. Levels of transcription factors were tested by qPCR. RESULTS: Analysis of transcriptome data for 23,000 single cells revealed 16 subpopulations. Luminal epithelial cells (LE) were further identified as five clusters. In SRD5A2-/- mice, while the total number of LE cells decreased, the percentage of LE2 subcluster increased. LE2, a predominant high expressor of estrogen receptor alpha (ESR1), was predominately located in the anterior prostate with enriched gene ontology (GO) terms of Wnt and MAPK signaling pathways. Zfp143, the transcription factor of ESR1, was dramatically upregulated in the absence of SRD5A2. CONCLUSIONS: Our data demonstrate the heterogeneity of cell populations within the mouse prostate. LE2, with an enhanced estrogen response gene signature, may play an important role in alternative pathways for prostate growth in the absence of SRD5A2. Understanding the underlying androgen-independent pathways contributing to prostate growth can help identify novel therapeutic targets for the management of prostatic diseases. Source of Funding: National Institutes of Health (NIH)/ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH/R01 DK124502) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e271 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Christina Sharkey More articles by this author Xingbo Long More articles by this author Ra'ad Al-Faouri More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Recent results of HDR brachytherapy in the treatment of localized forms of prostate cancer

Background. High levels of prostate cancer incidence require the search for more effective therapy methods. Interstitial brachytherapy is widely used in the treatment of localized prostate cancer. Purpose – to evaluate the current possibilities of HDR brachytherapy using a 60CO source during radiation therapy in treatment of localized prostate cancer. Materials and Methods. 47 patients with stage II–III prostate cancer who received HDR brachytherapy in combination with EBRT (43 patients) or in mono-mode (4 patients) were examined. The low-risk group included 2 patients (4,3%), the moderate-risk group consisted of 25 patients (53,2%), and the high-risk group included 20 patients (42,5%). The initial mean PSA level was 12,9 ng/ml. The volume of the prostate varied from 17,8 to 57 cm3, the average value was 38,4 cm3. In most patients, the tumor size corresponded to T2 (55,3%). Histologically tumors in all cases corresponded to adenocarcinoma. Results. Evaluation of surgical complications showed: macrohematuria – in 23,4% of cases, acute urethritis – in 6,4% of cases, obstruction symptom – in 4,3%. PSA levels were assessed at 2 months after radiation treatment. The tumor marker ranged from 0,07 to 7,81 ng/ml, the average PSA value was 1,79 ng/ml. MRI examination after 3 months showed that regression of tumor foci and reduction of prostate size was observed in (88,8 ± 6,1)% of patients in the low and intermediate risk groups and in (65,0 ± 10,6)% of cases in the high risk group. After combined radiation treatment: dysuric phenomena of the 1st–2nd grade (RTOG) was diagnosed in 16 patients (37,2%), radiation rectitis of the 1st grade was observed in 4 patients (9,3%). A temporary decrease in sexual function was reported in 2 patients (4,2%). 83% of patients overcame the two-year recurrence-free period: (95,7 ± 3,9)% of patients in the low and intermediate risk groups and in (70,0 ± 10,2)% cases in the high risk group Conclusions. Conducting HDR brachytherapy in terms of combined radiation therapy in patients with localized prostate cancer makes it possible to deliver higher doses of radiation to the tumor volume without the increase in radiation toxicity