World Journal of Mens Health最新文献

Purpose: To develop a noble on-site dual screening system for sperm concentration and hyaluronidase (HAdase) activity of male fertility based on lateral-flow assay methods, and to evaluate the effectiveness of this dual screening system.

Materials and methods: A chromogenic reaction for sperm count was established using a sperm-specific antibody against sperm antigen-10 (SP-10). Substrate-enzyme reaction was developed in which the activity of sperm HAdase on hyaluronic acid (HA) substrates could be measured through a color reaction. The colored HA substrates were degraded and the color faded by the sperm HAdase. To evaluate the validity of the developed methods, the results were compared using 49 semen samples (normozoospermia, 20; oligozoospermia, 9; azoospermia, 20) whose sperm counts were confirmed by the conventional method.

Results: Using color reaction by SP-10, no signal was observed in azoospermia and low count of sperm (<16×10⁶/mL), and the color signal increased as the count of sperm increased in normal and high count of sperm (≥16×10⁶/mL). The assay system for sperm HAdase activity was successfully developed. In the HAdase assay, the stronger the enzyme activity, the lower the color signal. Through statistical analysis, it was confirmed that there was a statistically significant correlation between sperm count and HAdase activity.

Conclusions: It was successfully developed that a novel on-site dual screening system for sperm count and HAdase activity, simultaneously. We are expecting that this novel dual assay system will provide the accessible and useful information about male fertility at on-site or home.

In the field of male health, disorders of the reproductive and urological systems present significant challenges. The global increase in male infertility, primarily attributed to environmental and lifestyle factors, along with the high incidence of urological cancers, not only places a significant socio-economic burden but also emphasizes the urgent need for in-depth research. Epigenetic modifications, especially N6-methyladenosine (m6A) methylation, are of great importance in these conditions. m6A, which is regulated by specific "writer", "eraser", and "reader" proteins, has an impact on various RNA-related processes. This review summarizes the regulatory functions of m6A in male reproductive health and urological cancers. In male reproduction, it explores how m6A affects somatic cell functions, steroidogenesis, and the blood-testis barrier. It also delves into its role in diabetic erectile dysfunction and benign prostatic hyperplasia. In urological cancers, the review examines m6A's influence on metabolic reprogramming, programmed cell death, and tumor immunity. Furthermore, this review discusses the potential of targeting m6A as a therapeutic approach for these conditions. By integrating recent research findings, it offers new perspectives on the role of m6A in male reproductive and urological disorders, laying a foundation for future research.

Purpose: This study aims to investigate the bidirectional causal relationship between erectile dysfunction (ED) and cerebral cortical structure.

Materials and methods: This study employed bidirectional two-sample Mendelian randomization (MR) framework. Exposure and outcome data were derived from genome-wide association study (GWAS) datasets. The MR analysis incorporated inverse variance weighted regression as the primary method, supplemented by the weighted median method and MR-Egger regression, to evaluate causal relationships between ED and brain cortical structure metrics, including surface area (SA) and cortical thickness (TH). Cerebral cortical morphology in ED patients was assessed using 3D T1-weighted magnetic resonance imaging (MRI).

Results: Whole-brain analysis demonstrated no significant association between ED and global SA or TH. Regional analyses revealed that ED was associated with reduced SA of the caudal anterior cingulate gyrus, increased SA of the insula, operculum, pars triangularis, and supramarginal gyrus, as well as increased TH of the insula and decreased TH of the transverse temporal gyrus. Regarding the effects of cerebral cortical characteristics on incidence of ED, TH in the inferior parietal gyrus, medial orbitofrontal gyrus, posterior cingulate gyrus, precentral gyrus and SA of cuneus exhibited significant effects on elevated risk of ED. Furthermore, the structure of insula, pars opercularis and precentral gyrus was further confirmed by MRI as associated with ED symptoms.

Conclusions: ED has been identified to be associated with structural alterations in multiple brain regions, suggesting potential associations with impairments in cognitive function, regulation of language processing, and sensory integration. Moreover, alterations in cortical structures of specific brain regions may serve as a predictor of ED incidence, offering novel insights for future prevention and therapeutic interventions. Overall, our results indicate the existence of a potential bidirectional interaction between genital sensory pathways and central neurological processes.

Purpose: Epidermal growth factor-like 7 (EGFL7) has been implicated in various cancers, but its role in different stages of prostate cancer (PCa), particularly metastatic castration-resistant prostate cancer (mCRPC), remains unclear. This study aimed to investigate the biological function of EGFL7 and its association with immune regulation in PCa.

Materials and methods: We quantified EGFL7 and intercellular adhesion molecule-1 (ICAM-1) levels in serum and prostate tissue specimens from patients with benign prostatic hyperplasia (BPH), localized PCa, and mCRPC. To explore its functional role, EGFL7 expression was either silenced or overexpressed in DU145 and PC3 cells using siRNA or pCMV-GFP, respectively. Xenograft experiments were conducted in nude mice using transfected DU145/PC3 cells, followed by post-hoc microarray analysis of tumor tissues.

Results: Our findings revealed that EGFL7 expression was significantly higher in both serum and tumor tissues of mCRPC patients compared to those with BPH or localized PCa. ICAM-1 levels were inversely correlated with EGFL7 expression. Knockdown of EGFL7 in DU145 cells suppressed cell proliferation, migration, and invasion, while in vivo studies demonstrated that EGFL7 silencing inhibited tumor growth and increased ICAM-1 expression along with CD4/8 lymphocyte infiltration. Conversely, overexpression of EGFL7 in PC3 cells promoted tumor progression and reduced ICAM-1 levels.

Conclusions: These findings suggest that EGFL7 overexpression in mCRPC suppresses immune cell infiltration by downregulating endothelial ICAM-1. Our study highlights the potential of EGFL7 as a therapeutic target in advanced PCa.

Purpose: This study explores whether certain trace elements are genetically linked to male infertility by using large-scale genetic data and a method called Mendelian randomization (MR), which helps infer causal relationships.

Materials and methods: We obtained genetic data related to trace minerals and iron metabolism from three databases: the IEU Open GWAS, UK Biobank, and FinnGen Biobank. We used standard MR analysis tools to evaluate the relationship between genetic variants associated with trace elements and the risk of male infertility. The main analysis was performed using a statistical approach called the inverse variance-weighted method. Heterogeneity, horizontal pleiotropy, and potential outliers in the MR analysis results were evaluated.

Results: The analysis suggested that higher genetically predicted iron levels may increase the risk of male infertility (odds ratio, 2.917; 95% confidence interval: 1.232-6.911; p=0.015). No similar associations were found for other elements such as copper, selenium, zinc, potassium, magnesium, calcium, ferritin, transferrin saturation, or total iron-binding capacity. The results were consistent across different analyses, with no signs of bias or genetic confounding.

Conclusions: This study provides genetic support for a possible causal role of iron in male infertility. Further research, including clinical and experimental studies, is needed to confirm these findings.

Exosomes, which are membrane-bound vesicles with diameters of 30 to 150 nanometers, are secreted by nearly all cell types and serve as key mediators of intercellular communication. In the male reproductive system, exosomes originating from reproductive glands, including the testes, epididymis, and prostate, transport proteins, lipids, and nucleic acids, thereby regulating sperm function, maturation, and fertilization. Exosomes facilitate intercellular communication by transporting bioactive molecules (particularly microRNAs), and are instrumental in sperm maturation, motility, and fertilization capacity. However, exosomes exhibit dual roles in male reproductive processes, as their mechanisms of action are highly context-dependent, depending on the molecules they carry and the microenvironment in which they function. This review aims to summarize the dual regulatory functions of seminal plasma exosomes in male infertility, with a focus on their roles in spermatogenesis, sperm maturation, and fertilization. Furthermore, the potential of exosomes as biomarkers for diagnosing and treating male infertility is examined. Despite the promising application of exosomes in male reproductive health, further studies are required to elucidate their mechanisms, offering new perspectives for precise interventions in male infertility and enhancing assisted reproductive technologies.

Benign prostatic hyperplasia and prostate cancer (PC) frequently affect aging men, both involving irregular cell growth in the prostate. Inflammation is a major contributor to these conditions, whereas DNA methylation and hydroxymethylation are specifically involved in PC development. In this review, we address several potential factors influencing the progression of PC, including DNA epigenetic marks, ascorbate (vitamin C) concentration in the blood plasma, and its intracellular levels in leukocytes and prostate tissues. Moreover, a new aspect concerning the involvement of leukocytes (white blood cells) in PC formation will also be discussed, highlighting their potential utility for assessing early PC development through a minimally invasive approach.

The human body harbors a complex, dynamic community of trillions of microbes, collectively termed the microbiota, which profoundly affects homeostasis and disease processes, including cancer. Prostate cancer remains a major cause of morbidity and mortality among men worldwide; however, critical questions remain regarding its etiology, progression, and resistance to therapy. Multiple epidemiological studies have found associations between certain urinary and intestinal microorganisms and an increased prostate cancer risk, although the causal mechanisms remain incompletely understood. Recent studies suggest that dysregulated microbial communities, or dysbiosis, are hypothesized to drive chronic inflammation, induce genotoxic insults, and modulate steroid metabolism, thereby influencing tumor initiation and progression. Conflicting findings across different investigations often stem from heterogeneous sampling methods, population differences, and disparate bioinformat ics pipelines, underscoring the critical need for standardized protocols and reproducible data analytics. For example, diet induced alterations in the gut microbiota can shift systemic inflammatory and hormonal pathways in ways that predispose individuals to malignant transformation. Simultaneously, prostatic and urinary microbes are hypothesized to fuel local inflam mation and promote precursor lesions, although whether this microbial activity is causative or merely reflective of the exist ing tumor biology remains a key unresolved question. Microbiota-driven mechanisms also shape responses to radiotherapy, chemotherapy, and emerging immunotherapies, highlighting the potential of interventions such as probiotics, prebiotics, and fecal microbiota transplantation to enhance treatment efficacy and mitigate side effects. Innovative approaches, including ar tificial intelligence-assisted predictive modeling, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based microbial gene editing, and immunomodulatory strategies (e.g., chimeric antigen receptor-T cells), offer new avenues for exploiting microbiota for therapeutic benefits. Nevertheless, unresolved questions regarding the long-term safety, ecological balance, and individual patient factors require caution. By integrating rigorous methodologies with these novel technologies, prostate cancer research may ultimately harness microbial insights to refine diagnostic tools, personalize therapies, and im prove patient outcomes.

Purpose: This study aimed to evaluate the efficacy and safety of mirabegron and tamsulosin combination therapy compared to tamsulosin monotherapy in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS).

Materials and methods: This phase 3, randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of mirabegron/tamsulosin combination therapy versus tamsulosin monotherapy in men with LUTS. The trial, conducted across 25 centers from July 2021 to October 2023. Eligible participants were randomly assigned to either the combination or monotherapy group for 12 weeks. Primary efficacy endpoints included changes in total urinary frequency score (TUFS) and International Prostate Symptom Scores (IPSS), with secondary endpoints evaluating various urinary symptoms and changes in post void residual volume (PVR), maximum urinary flow rate (Qmax), and quality of life scores. Safety assessments included adverse events, PVR, Qmax, vital signs, electrocardiogram, and laboratory tests.

Results: A total of 795 participants were randomized to monotherapy (n=397) and combination therapy (n=398) groups. After 12 weeks, 342 in the monotherapy and 339 in the combination therapy group completed the study, with no significant baseline differences. The combination therapy group showed a greater improvement in TUFS (-11.28) and IPSS (-10.85) scores compared to monotherapy (-8.30 and -9.85, respectively) with significant differences (p<0.0001, p=0.0325). Combination therapy showed significant improvements in storage symptoms and voiding diary variables, including daytime frequency, urgency, and incontinence, compared to monotherapy. The incidence of treatment-emergent adverse events was similar between the groups (13.10% vs 16.58%, p=0.1943), with no serious drug-related adverse events, confirming an acceptable safety profile for combination therapy.

Conclusions: Combination therapy with mirabegron and tamsulosin is more effective than monotherapy in improving LUTS in patients with BPH, particularly storage symptoms, with a comparable safety profile. A fixed-dose combination formulation in the future may further improve patient adherence and quality of life.

Purpose: Current research suggests a correlation between erectile dysfunction (ED) and dietary-derived antioxidants. However, the causal relationship between these factors remains unclear. This study aims to investigate the causal relationship between dietary-derived antioxidants and ED using Mendelian randomization (MR) analysis, based on genetic prediction.

Materials and methods: This study employed bidirectional two-sample MR analysis to investigate the causal relationship between dietary-derived antioxidants and ED. The primary results were based on inverse variance-weighted analysis with random effects. To assess the robustness and reliability of the findings, sensitivity analyses were conducted, including tests for heterogeneity, horizontal pleiotropy, and leave-one-out analysis. Additionally, multivariate MR analysis was performed to further validate the robustness of the results.

Results: The inverse variance-weighted results revealed a significant causal relationship between plasma vitamin A levels and ED (odds ratio [OR]: 3.44; 95% confidence interval [95% CI]: 1.22-9.68; p=0.019), suggesting that elevated plasma vitamin A levels are a risk factor for ED. A reverse causal relationship was observed between ED and carotene levels (OR: 0.97, 95% CI: 0.95-1.00; p=0.04). After adjusting for smoking status, the causal association between vitamin A and ED remained significant. The heterogeneity test indicated variability in the relationship between carotene and ED, while the pleiotropy test revealed that the MR-PRESSO p-value for zinc and ED was less than 0.05.

Conclusions: This study identifies specific causal relationships between dietary antioxidants and ED, providing a foundation for understanding the pathogenesis of ED, guiding the development of dietary intervention strategies, and informing clinical treatment approaches.