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International Journal of Biological... 2023Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The...
Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The study used Weighted Gene Co-Expression Network Analysis, as well as two machine learning strategies to identify BPH-specific biomarkers based on an integrated transcriptome data from 922 samples. Eight prognostic genes (, , , , , , , and ) were identified to be BPH-specific biomarkers with high accuracy and specificity. Moreover, we constructed a seven-gene diagnostic classifier to distinguish BPH from PC. The infiltrations of plasmacytoid dendritic cells and neutrophil cells showed distinct differences between BPH and non-BPH groups. Additionally, ursolic acid can reverse transcriptional features associated with the occurrence and progression of BPH. Both and experiments have confirmed that it induces apoptosis of BPH cells and inhibits cell proliferation by promoting cell cycle S-phase arrest. The diagnostic biomarkers, microenvironment characteristics, and therapeutic effect of ursolic acid explored in this study offer new diagnostic and therapeutic strategies for BPH.
Topics: Male; Humans; Prostatic Hyperplasia; Prostate; Hyperplasia; Prostatic Neoplasms; Tumor Microenvironment; Forkhead Transcription Factors; Cell Adhesion Molecules; Ursolic Acid
PubMed: 37705744
DOI: 10.7150/ijbs.85739 -
Aging Clinical and Experimental Research Jan 2024Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia...
BACKGROUND
Circulating metabolites (CM) play a pivotal role in our overall health, yet the current evidence concerning the involvement of diverse CM in benign prostatic hyperplasia (BPH) remains limited. Mendelian randomization (MR) offers a promising avenue to explore the potential impact of CM on BPH.
METHODS
In a forward MR analysis, a cohort of 249 circulating metabolites was employed as exposures to investigate their potential associations with BPH risk. Conversely, in a reverse MR analysis, BPH was employed as an exposure to assess its effects on CM.
RESULTS
The forward MR analysis discerned a linkage between six metabolites and BPH, with careful consideration to excluding heterogeneity and pleiotropy. Subsequently, the reverse MR analysis unveiled that nine metabolic compounds, mainly comprising phospholipids and triglycerides, potentially exhibit elevated levels in BPH patients.
CONCLUSION
Bidirectional MR analysis furnishes genetic insight into the interplay between CM and BPH. The prominence of lipids and triglycerides emerges as significant factors intricately linked to BPH risk.
Topics: Male; Humans; Prostatic Hyperplasia; Hyperplasia; Mendelian Randomization Analysis; Prostate; Triglycerides
PubMed: 38281223
DOI: 10.1007/s40520-023-02669-4 -
Diabetes, Metabolic Syndrome and... 2023Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of...
INTRODUCTION
Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, the role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic symptoms appears feasible but is still unknown. In fact, a connection between metabolic syndrome and BPH is becoming increasingly evident from epidemiologic studies. Key factors of Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) are increased prostate smooth muscle tone, and prostate enlargement. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells.
METHODS
We performed microarray analysis to identify genes (fold change ≥ 1.5) associated with BPH/LUTS progression, such as those involved in proliferation, apoptosis, and mitochondrial metabolism, in rat prostate tissue (data from GSE129561). We then used electric field stimulation (EFS) to induce frequency-dependent, neurogenic contractions of human prostate strips, which were enhanced by leptin. We also examined the effect of leptin on human prostate stromal cells (WPMY-1) and found increased cell proliferation and viability upon exposure. To explore the underlying mechanism, we conducted mitochondrial stress assay using near-infrared (NIR) fluorescent dye and flow cytometry (FACS) analysis and observed reduced cellular apoptosis and preserved mitochondrial membrane potential (∆ψM) after leptin treatment.
RESULTS
Microarray analysis reveals that leptin regulates prostate smooth muscle contraction and stromal cell proliferation, shedding new light on its involvement in BPH/LUTS pathogenesis and mitochondrial function. We found that leptin enhanced the proliferation rate of prostate stromal cells relative to the control group (0.67 ± 0.05 vs 0.54 ± 0.08, p-value= 0.024). Moreover, leptin (100 ng/mL) potentiated the frequency-dependent, neurogenic contractions of prostate strips elicited by EFS (p= 0.047 between leptin and control group). We also show that leptin treatment increased the mitochondrial membrane potential of prostate stromal cells and inhibited mitochondrial apoptosis.
DISCUSSION
Our results indicate that leptin stimulates the contractility and proliferation of smooth muscle and stromal cells in the human prostate, implying a potential role for leptin in exacerbating BPH/LUTS in obese men. Leptin modulation may be a beneficial therapeutic strategy for patients with metabolic syndrome and BPH/LUTS. Further studies are warranted to elucidate the mechanisms and implications of the leptin system in BPH/LUTS.
PubMed: 37876983
DOI: 10.2147/DMSO.S420258 -
Croatian Medical Journal Dec 2023To compare the indicators of the spatial organization of collagen and its regulating factors between benign and malignant prostate neoplasms.
AIM
To compare the indicators of the spatial organization of collagen and its regulating factors between benign and malignant prostate neoplasms.
METHODS
The study involved tumor tissue samples from 40 patients with stage II-III prostate cancer (PCa) and 20 patients with benign prostatic hyperplasia (BPH). The localization of collagen was determined with a Masson trichrome stain. To establish quantitative indicators of the spatial organization of collagen, morphometric studies were carried out with the CurveAlign and ImageJ programs.
RESULTS
PCa tissue had two times lower collagen density (P<0.0001) and 1.3 times lower levels of collagen alignment (P=0.018) compared with BPH tissue. In PCa tissue, collagen fibers were shorter (by 24.2%; P<0.001) and thicker (by 15.5%; P<0.001). PCa tissue samples showed significantly higher levels of metalloproteinase (MMP)-2 (by 2.4 times; P=0.001), MMP-8 (by 2.3 times; P=0.007), and MMP-13 (by 1.9 times; P=0.004).
CONCLUSIONS
Collagen matrix spatial organization features, as well as its regulatory factors, could be potential biomarkers of malignant prostate neoplasms.
Topics: Male; Humans; Prostatic Hyperplasia; Prostatic Neoplasms; Biomarkers; Collagen
PubMed: 38168522
DOI: 10.3325/cmj.2023.64.413 -
Cancers Jun 2023Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate... (Review)
Review
Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases.
PubMed: 37370720
DOI: 10.3390/cancers15123110 -
Molecular Medicine (Cambridge, Mass.) Oct 2023The pathogenesis of benign prostatic hyperplasia (BPH) has not been fully elucidated. Ras homology family member A (RhoA) plays an important role in regulating cell...
BACKGROUND
The pathogenesis of benign prostatic hyperplasia (BPH) has not been fully elucidated. Ras homology family member A (RhoA) plays an important role in regulating cell cytoskeleton, growth and fibrosis. The role of RhoA in BPH remains unclear.
METHODS
This study aimed to clarify the expression, functional activity and mechanism of RhoA in BPH. Human prostate tissues, human prostate cell lines, BPH rat model were used. Cell models of RhoA knockdown and overexpression were generated. Immunofluorescence staining, quantitative real time PCR (qRT-PCR), Western blotting, cell counting kit-8 (CCK-8), flow cytometry, phalloidine staining, organ bath study, gel contraction assay, protein stability analysis, isolation and extraction of nuclear protein and cytoplasmic protein were performed.
RESULTS
In this study we found that RhoA was localized in prostate stroma and epithelial compartments and was up-regulated in both BPH patients and BPH rats. Functionally, RhoA knockdown induced cell apoptosis and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transformation (EMT) and contraction. Consistently, overexpression of RhoA reversed all aforementioned processes. More importantly, we found that β-catenin and the downstream of Wnt/β-catenin signaling, including C-MYC, Survivin and Snail were up-regulated in BPH rats. Downregulation of RhoA significantly reduced the expression of these proteins. Rho kinase inhibitor Y-27632 also down-regulated β-catenin protein in a concentration-dependent manner. However, overexpression of β-catenin did not affect RhoA-ROCK levels, suggesting that β-catenin was the downstream of RhoA-ROCK regulation. Further data suggested that RhoA increased nuclear translocation of β-catenin and up-regulated β-catenin expression by inhibiting its proteasomal degradation, thereby activating Wnt/β-catenin signaling. Overexpression of β-catenin partially reversed the changes in cell growth, fibrosis and EMT except cell contraction caused by RhoA downregulation. Finally, Y-27632 partially reversed prostatic hyperplasia in vivo, further suggesting the potential of RhoA-ROCK signaling in BPH treatment.
CONCLUSION
Our novel data demonstrated that RhoA regulated both static and dynamic factors of BPH, RhoA-ROCK-β-catenin signaling axis played an important role in the development of BPH and might provide more possibilities for the formulation of subsequent clinical treatment strategies.
Topics: Animals; Humans; Male; Rats; beta Catenin; Cell Proliferation; Fibrosis; Prostatic Hyperplasia; Wnt Signaling Pathway
PubMed: 37864185
DOI: 10.1186/s10020-023-00734-2 -
Frontiers in Endocrinology 2023Surgical treatment is important for male lower urinary tract symptom (LUTS) management, but there are few reviews of the risks of reoperation. (Meta-Analysis)
Meta-Analysis
CONTEXT
Surgical treatment is important for male lower urinary tract symptom (LUTS) management, but there are few reviews of the risks of reoperation.
OBJECTIVE
To systematically evaluate the current evidence regarding the reoperation rates of surgical treatment for LUTS in accordance with current recommendations and guidelines.
EVIDENCE ACQUISITION
Eligible studies published up to July 2023, were searched for in the PubMed (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, the Netherlands), and Web of Science™ (Clarivate™, Philadelphia, PA, USA) databases. STATA (StataCorp LP, College Station, TX, USA) software was used to conduct the meta-analysis. Random-effects models were used to calculate the pooled incidences (PIs) of reoperation and the 95% confidence intervals (CIs).
EVIDENCE SYNTHESIS
A total of 119 studies with 130,106 patients were included. The reoperation rate of transurethral resection of the prostate (TURP) at 1, 2, 3, and 5 years was 4.0%, 5.0%, 6.0%, and 7.7%, respectively. The reoperation rate of plasma kinetic loop resection of the prostate (PKRP) at 1, 2, 3, and 5 years was 3.5%, 3.6%, 5.7%, and 6.6%, respectively. The reoperation rate of holmium laser enucleation of the prostate (HoLEP) at 1, 2, 3, and 5 years was 2.4%, 3.3%, 5.4%, and 6.6%, respectively. The reoperation rate of photoselective vaporization of the prostate (PVP) at 1, 2, 3, and 5 years was 3.3%, 4.1%, 6.7%, and 7.1%, respectively. The reoperation rate of surgery with AquaBeam at 1, 2, 3, and 5 years was 2.6%, 3.1%, 3.0%, and 4.1%, respectively. The reoperation rate of prostatic artery embolization (PAE) at 1, 2, 3, and 5 years was 12.2%, 20.0%, 26.4%, and 23.8%, respectively. The reoperation rate of transurethral microwave thermotherapy (TUMT) at 1, 2, 3, and 5 years was 9.9%, 19.9%, 23.3%, and 31.2%, respectively. The reoperation rate of transurethral incision of the prostate (TUIP) at 5 years was 13.4%. The reoperation rate of open prostatectomy (OP) at 1 and 5 years was 1.3% and 4.4%, respectively. The reoperation rate of thulium laser enucleation of the prostate (ThuLEP) at 1, 2, and 5 years was 3.7%, 7.7%, and 8.4%, respectively.
CONCLUSION
Our results summarized the reoperation rates of 10 surgical procedures over follow-up durations of 1, 2, 3, and 5 years, which could provide reference for urologists and LUTS patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023445780.
Topics: United States; Humans; Male; Prostatic Hyperplasia; Transurethral Resection of Prostate; Prostate; Reoperation; Embolization, Therapeutic; Lower Urinary Tract Symptoms
PubMed: 38027158
DOI: 10.3389/fendo.2023.1287212 -
Advanced Science (Weinheim,... Feb 2024Chronic prostatic inflammation promotes cell survival and fibrosis, leading to benign prostatic hyperplasia (BPH) with aggravated urinary symptoms. It is investigated...
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.
Topics: Animals; Humans; Male; Rats; Adaptor Proteins, Signal Transducing; Cell Line; Cell Survival; Fibrosis; Inflammation; Prostatic Hyperplasia; rho-Associated Kinases; Transcription Factors
PubMed: 38050650
DOI: 10.1002/advs.202304274 -
Oncology Letters Sep 2023The present study explored the clinical value of the protein expression levels of nucleotide binding oligomerization-like receptor family pyrin domain containing 1...
The present study explored the clinical value of the protein expression levels of nucleotide binding oligomerization-like receptor family pyrin domain containing 1 (NLRP1) and nucleotide-binding oligomerization domain leucine-rich repeat and caspase recruitment domain-containing 4 (NLRC4) inflammasomes in the diagnosis and treatment of prostate cancer. A total of 54 patients with prostatic hyperplasia and 58 patients with prostate cancer were recruited at The First People's Hospital of Pinghu between January and May 2022. Immunohistochemical staining was used to determine the protein expression levels of the NLRP1 and NLRC4 inflammasomes in addition to the proinflammatory cytokines IL-18 and IL-1β in the two groups of patients. The protein expression levels of NLRP1 and NLRC4 inflammasome were significantly increased in patients with prostate cancer compared with patients with prostate hyperplasia. The differences in expression of NLRP1 and NLRC4 inflammatory vesicles in prostate cancer of different stages were also compared based on data from The Cancer Genome Atlas. The protein expression level of NLRP1 demonstrated a significant positive correlation with IL-1β and IL-18 expression, and the protein expression level of the NLRC4 inflammasome was significantly positively correlated with IL-18 expression. The protein expression levels of both NLRP1 and NLRC4 demonstrated a significant positive correlation with the Gleason score of prostate cancer. The expression of NLRP1 in tumor (T)3/T4 was significantly higher compared with T1 and expression of the NLRC4 inflammasome in T2 and T3/T4 was significantly higher compared with T1. Expression of the NLRP1 and NLRC4 inflammasomes was significantly higher in patients with prostate cancer, compared with patients with prostatic hyperplasia. Therefore, expression of NLRP1 and NLRC4 may promote tumorigenesis by promoting the maturation and release of proinflammatory cytokines IL-1β and IL-18. Expression of the NLRP1 and NLRC4 inflammasomes demonstrated a significant positive correlation with the risk of prostate cancer. Expression of the NLRP1 and NLRC4 inflammasomes in middle- and advanced-stage tumors was higher compared with early-stage tumors. These results suggested that inflammasome expression may serve a significant role in the progression of tumors and could provide a fixed value for the risk assessment and prognosis prediction of prostate cancer.
PubMed: 37559581
DOI: 10.3892/ol.2023.13971 -
Frontiers in Immunology 2023COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of...
BACKGROUND
COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms.
METHODS
We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses.
RESULTS
We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH.
CONCLUSION
Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.
Topics: Humans; Male; Prostatic Hyperplasia; COVID-19; SARS-CoV-2; Genes, cdc; Algorithms
PubMed: 37426635
DOI: 10.3389/fimmu.2023.1172724