Search Results (75)

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Background: Prostate cancer is a leading malignancy among men globally, with its incidence expected to rise due to aging populations and shifting lifestyles. While established risk factors include age, ethnicity, and genetics, the role of modifiable dietary factors, particularly sugar intake, remains less clear. Emerging evidence suggests that high sugar consumption may promote carcinogenesis through insulin resistance, chronic inflammation, and hormonal dysregulation. This systematic review aimed to evaluate the current evidence on the association between dietary sugar intake and prostate cancer risk. Methods: A systematic search was conducted across six databases for observational studies published between January 2005 and April 2025. Eligible studies assessed the associations between quantitative sugar intake and prostate cancer outcomes. Screening, data extraction, and a risk of bias assessment (using ROBINS-E) were performed independently by multiple reviewers. Results: Six studies met the inclusion criteria, comprising four prospective cohorts, one case–control study, and one cross-sectional study, with a combined sample of 11,583 men from the USA, Canada, Sweden, and France. Three studies reported a significant positive association between a high intake of dietary sugars and prostate cancer risk, two found no association, and one showed mixed findings depending on the type of sugar. Heterogeneity in the exposure assessments and confounder control limited the comparability. Conclusions: This review suggests a possible association between high dietary sugar intake and increased prostate cancer risk, especially from added sugars and sugar-sweetened beverages. However, inconsistent findings and methodological limitations highlight the need for robust, prospective studies with standardized assessments to understand this relationship better. Full article

Background/Objectives: Currently, the Meares–Stamey 4-glass and the 2-glass tests are used for diagnosing chronic prostatitis subtypes. Both tests include prostatic massage. Failure to extract prostatic secretions—for any reason—can result in a non-diagnostic test. Evidence from everyday practice and studies shows that expressed prostatic secretions are successfully recovered in less than 50% of the examined patients, and an important number of post-massage urine samples are missing prostatic secretions. This study evaluated a simpler test, the 3-glass (pre-ejaculation, ejaculation, and post-ejaculation) test. We compared it with the 4-glass and the 2-glass tests to detect inflammation and bacteria in men with chronic prostatitis symptoms. Methods: The study population included patients with chronic prostatitis symptoms. Subjects were assigned in each visit to undergo either the 4-glass, the 2-glass test, or the 3-glass test. The comparison among the three tests was based on the percentage of bacterial detection, the percentage of false-negative diagnoses, and the percentage of shifts among chronic prostatitis subtypes in the follow-up visits of recurrent patients. Results: A total of 157 patients were finally evaluated. Fifty-nine (59) patients underwent the 4-glass test (Group A), sixty-seven (67) underwent the 3-glass test (Group B), and thirty-one (31) underwent the 2-glass test (Group C). No statistically significant differences in the comparisons above were found. Conclusions: A comparison of the three diagnostic tests showed equivalence of the total ejaculate culture-based 3-glass test to the conventional prostatic secretion culture-based tests. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article

Cardiovascular diseases and cancer are the two primary causes of mortality worldwide. Although traditionally regarded as distinct pathologies, they share numerous pathophysiological mechanisms and risk factors, including chronic inflammation, insulin resistance, obesity, and metabolic dysregulation. Notably, several cancers have been identified as closely linked to cardiovascular diseases, including lung, breast, prostate, and colorectal cancers, as well as hematological malignancies, such as leukemia and lymphoma. Additionally, renal and pancreatic cancers exhibit a significant association with cardiovascular complications, partly due to shared risk factors and the cardiotoxic effects of cancer therapies. Addressing the overlapping risk factors through lifestyle modifications—such as regular physical activity, a balanced diet, and cessation of smoking and alcohol—has proven effective in reducing both CV and oncological morbidity and mortality. Furthermore, even in patients with established cancer, structured interventions targeting physical activity, nutritional optimization, and smoking cessation have been associated with improved outcomes. Beyond lifestyle modifications, pharmacological strategies play a crucial role in the prevention of both diseases. Several cardiovascular medications, including statins, aspirin, beta-blockers, and metformin, exhibit pleiotropic effects that extend beyond their primary indications, demonstrating potential anti-neoplastic properties in preclinical and observational studies. Recently, novel therapeutic agents have garnered attention for their possible cardioprotective and metabolic benefits. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is), initially developed for managing type 2 diabetes, have shown CV and renal protective effects, alongside emerging evidence of their role in modulating cancer-related metabolic pathways. Inclisiran, a small interfering RNA targeting PCSK9, effectively lowers LDL cholesterol and may contribute to reducing CV risk, with potential implications for tumor biology. Additionally, sacubitril/valsartan, an angiotensin receptor–neprilysin inhibitor, has revolutionized heart failure management by improving hemodynamic parameters and exerting anti-inflammatory effects that may have broader implications for chronic disease prevention. Given the intricate interplay between CVD and cancer, further research is essential to clarify the exact mechanisms linking these conditions and assessing the potential of CV therapies in cancer prevention. This review aims to examine shared risk factors, consider the role of pharmacological and lifestyle interventions, and emphasize crucial epidemiological and mechanistic insights into the intersection of CV and oncological health. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is among the most common conditions affecting men as they age, resulting in lower urinary tract symptoms (LUTS) that can profoundly impact quality of life. While historically attributed primarily to androgenic imbalances, current evidence implicates additional factors—particularly oxidative stress (OS) and chronic inflammation—in BPH pathogenesis. This review aims to synthesize research on the interplay between OS, inflammation, and hormonal regulation in BPH, emphasizing their clinical relevance and potential therapeutic implications. Methods: A comprehensive review of peer-reviewed literature was conducted focusing on mechanistic studies, clinical trials, and observational reports. Searches included data on ROS generation, antioxidant capacity, inflammatory mediators, and their contribution to pathological prostatic overgrowth. Potential interventions targeting OS—such as antioxidant supplementation, anti-inflammatory drugs, vitamin D receptor agonists, and phytotherapeutics—were also evaluated for their efficacy and safety profiles. Results: Chronic inflammation and OS were consistently identified within hyperplastic prostate tissue. Excessive ROS production, diminished antioxidant defense, and sustained cytokine release create a proproliferative and antiapoptotic environment, accelerating disease progression. Metabolic comorbidities (e.g., obesity, insulin resistance) further exacerbate these imbalances. Standard therapies (α-blockers and 5-ARIs) effectively relieve symptoms but do not directly address the oxidative–inflammatory axis. Emerging evidence suggests that pharmacological and dietary approaches targeting OS and inflammation may reduce prostate volume expansion and alleviate LUTS. Conclusions: Findings indicate that OS and inflammation are key contributors to BPH progression. Incorporating antioxidant and anti-inflammatory strategies alongside conventional treatments holds promise for improving clinical outcomes and patient quality of life. Future research should focus on validating OS-specific biomarkers and optimizing personalized therapy regimens. Full article

Gamma-tocopherol (γ-tocopherol), a major isoform of vitamin E, exhibits potent antioxidant, anti-inflammatory, and anticancer properties, making it a promising therapeutic candidate for treating oxidative stress-related diseases. Unlike other tocopherol isoforms, γ-tocopherol effectively neutralizes reactive oxygen species (ROS) and reactive nitrogen species (RNS), providing robust cellular protection against oxidative damage and lipid peroxidation. Its anti-inflammatory effects are mediated through the modulation of pathways involving cyclooxygenase-2 (COX-2) and tumor necrosis factor-alpha (TNF-α), reducing chronic inflammation and its associated risks. In cancer therapy, γ-tocopherol demonstrates multifaceted activity, including the inhibition of tumor growth, induction of apoptosis, and suppression of angiogenesis, with significant efficacy observed in cancers such as prostate, lung, and colon. Preclinical and clinical studies support its efficacy in mitigating oxidative stress, inflammation, and cancer progression, with excellent tolerance at physiological levels. However, high doses necessitate careful evaluation to minimize adverse effects. This review consolidates current knowledge on γ-tocopherol’s biological activities and clinical implications, underscoring its importance as a natural compound for managing inflammation, oxidative stress, and cancer. As a perspective, advancements in nanoformulation technology could enhance γ-tocopherol’s bioavailability, stability, and targeted delivery, offering the potential to optimize its therapeutic application in the future. Full article

Chronic inflammation is a cancer hallmark and chronic exposure to interleukin-1 (IL-1) transforms castration-sensitive prostate cancer (PCa) cells into more fit castration-insensitive PCa cells. p62 is a scaffold protein that protects cells from nutrient deprivation via autophagy and from cytotoxic reactive oxygen via NFκB and NRF2 antioxidant signaling. Herein, we report that the LNCaP PCa cell line acquires high basal accumulation of the p62-KEAP1 complex when chronically exposed to IL-1. p62 promotes non-canonical NRF2 antioxidant signaling by binding and sequestering KEAP1 to the autophagosome for degradation. But despite high basal p62-KEAP1 accumulation, only two of several NRF2-induced genes analyzed, GCLC and HMOX1, showed high basal mRNA levels, suggesting that the high basal p62-KEAP1 accumulation does not result in overall high basal NRF2 activity. Nutrient starvation induces NRF2-dependent GCLC upregulation and HMOX1 repression, and we found that chronic IL-1-exposed LNCaP cells show hypersensitivity to serum starvation-induced GCLC and HMOX1 regulation. Thus, chronic IL-1 exposure affects cell response to nutrient stress. While HMOX1 expression remains NRF2/KEAP1-dependent in chronic IL-1-exposed LNCaP cells, GCLC expression is NRF2/KEAP1-independent. Furthermore, the high basal p62-KEAP1 complex accumulation is not required to regulate GCLC or HMOX1 expression, suggesting cells chronically exposed to IL-1 evolve a novel NRF2-independent role for the p62/KEAP1 axis. Full article

Background/Objectives: Several independent studies have associated prostate cancer (PCa) with specific groups of bacteria, most of them reporting the presence of anaerobic or microaerophilic species such as Cutibacterium acnes (C. acnes). Such findings suggest a prostate cancer-related bacterial dysbiosis, in a manner similar to the association between Helicobacter pylori infection and gastric cancer. In an earlier exploratory study looking for such dysbiosis events, using a culturomics approach, we discovered that the presence of obligate anaerobes (OAs) along with C. acnes was associated with increased prostate-specific antigen (PSA) levels in 39 participants. Methods: Building on this, in this study, we analyzed 89 post-rectal examination urine samples, from men with prostate cancer attending the PROVENT trial, using 16S rDNA sequencing. Our investigation focused on the impact of six previously identified OA genera (Finegoldia, Fusobacterium, Prevotella, Peptoniphilus_A, Peptostreptococcus, and Veillonella_A) on PSA levels. However, an additional data-driven approach was followed to uncover more taxa linked to increased PSA. Results: Our analysis revealed a statistically significant association between Peptostreptococcus and elevated PSA levels. Additionally, there were potential interactions between Prevotella and Fusobacterium. Interestingly, we also found that an aerobe, Ochrobactrum_A,was significantly linked to higher PSA levels. Conclusions: These findings suggest that OA-related dysbiosis may contribute to elevated PSA levels through prostate cell damage even before prostate cancer develops, possibly playing a role in chronic inflammation and the hypervascular changes seen in precancerous lesions. Future clinical trials with larger cohorts are needed to further evaluate the role of OA in prostate cancer development and progression. Full article

Background/Objectives: Prostate cancer is the second leading cause of cancer death among American men, following lung cancer. While diet and exercise have been extensively studied in relation to prostate cancer prevention, the evidence remains inconclusive. Methods: A comprehensive literature search was performed to identify observational studies investigating the association between ultra-processed food (UPF) consumption and prostate cancer risk and mortality, determined by the NOVA classification system. In addition, we conducted subgroup analyses to assess the association based on study design, age, and data collection methods. Results: Six studies were identified, including four cohort studies and two case–control studies. No significant association was found between high UPF consumption and increased risk of prostate cancer [RR = 1.02, 95% confidence interval (CI) = 0.96–1.08, n = 5]. However, there was a slight increase in mortality (RR = 1.15, 95% CI = 0.99–1.35, n = 2). A subgroup analysis by the dietary assessment method revealed an RR of 1.01 (95% CI = 0.93–1.09) for studies using the food frequency questionnaire (FFQ) and 1.04 (95% CI = 0.93–1.16) for studies using 24-h recalls. There was no significant heterogeneity among the studies (I² = 0, p = 0.82). Conclusions: This meta-analysis suggests no significant association between high UPF consumption and prostate cancer risk. Given the known associations with other chronic diseases, the potential public health implications of reducing UPF consumption remain important. Further research with the use of more robust food assignment systems and more precise dietary assessments is needed to clarify the role of UPF in prostate cancer development. Full article

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic DSF (De Simone formulation) in improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because the low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and DSF treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. Methods: We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n = 64) was treated with rifaximin (seven days per month for three months) followed by DSF, and group B (n = 60) was treated with a placebo. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI (National Institute of Health’s Chronic Prostatitis Symptom Index) and IBS-SSS (Irritable Bowel Syndrome Severity Scoring System) scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs. 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs. 4.4 pg/mL) relative to baseline, whereas the levels of IL-6 and IL-10 did not change in the placebo group. Conclusions: The combined treatment with rifaximin and DSF appears to represent the optimal approach for addressing a syndrome such as irritable bowel syndrome (IBS-D plus), which frequently co-occurs with prostatitis (IIIa prostatitis). This approach is particularly beneficial in cases where the symptoms are not always clearly delineated, the etiology is multifactorial, and the diagnosis is multilevel. Full article

Chronic inflammation is a recognized risk factor for various cancers, including prostate cancer (PCa). We aim to explore the potential protective effects of aged black garlic extract (ABGE) against inflammation-induced prostate damage and its impact on prostate cancer cell lines. We used an ex vivo model of inflammation induced by Escherichia coli lipopolysaccharide (LPS) on C57BL/6 male mouse prostate specimens to investigate the anti-inflammatory properties of ABGE. The gene expression levels of pro-inflammatory biomarkers (COX-2, NF-κB, and TNF-α, IL-6) were measured. Additionally, we evaluated ABGE’s therapeutic effects on the prostate cancer cell lines through in vitro functional assays, including colony formation, tumorsphere formation, migration assays, and phosphorylation arrays to assess the signaling pathways (MAPK, AKT, JAK/STAT, and TGF-β). ABGE demonstrated significant anti-inflammatory and antioxidant effects in preclinical models, partly attributed to its polyphenolic content, notably catechin and gallic acid. In the ex vivo model, ABGE reduced the gene expression levels of COX-2, NF-κB, TNF-α, and IL-6. The in vitro studies showed that ABGE inhibited cell proliferation, colony and tumorsphere formation, and cell migration in the prostate cancer cells, suggesting its potential as a therapeutic agent. ABGE exhibits promising anti-inflammatory and anti-cancer properties, supporting further investigation into ABGE as a potential agent for managing inflammation and prostate cancer. Full article

Reactive oxygen species (ROS) participate in almost all disorders, including cancer. Many factors, including aging, a high-fat diet, a stressful lifestyle, smoking, infection, genetic mutations, etc., lead to elevated levels of ROS. Prostate cancer, the most prevalent type of cancer in senior American men and the second leading cause of cancer mortality in American men, results from chronic oxidative stress. The doubled incident rate as well as the doubled mortality numbers of prostate cancer have persisted in African Americans in comparison with Caucasian Americans and other racial groups, indicating a prostate cancer disparity in African American men. In this review, we mainly focus on the latest findings on ROS in prostate cancer development and progression within the last five years to update our understanding in this area, as several comprehensive literature reviews addressing oxidative stress and/or inflammation in prostate cancer before 2020 are available. In addition to other known factors such as socioeconomic disadvantage, cultural mistrust of the health care system, etc. that are long-existing in the African American group, we also summarize the latest evidence that demonstrated high systemic oxidative stress and inflammation in African Americans for their potential contribution to the racial prostate cancer disparity in this population. Full article

Chronic inflammation is an important factor in the development of cancer. Macrophages found in tumors, known as tumor associated macrophages (TAMs), are key players in this process, promoting tumor growth through humoral and cellular mechanisms. 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), an arachidonic acid metabolite, has been described to possess a potent chemoattractant activity for human white blood cells (WBCs). The biological actions of 5-oxo-ETE are mediated through the GPCR 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor (OXER1). In addition, we have previously reported OXER1 as one of the membrane androgen receptors with testosterone antagonizing 5-oxo-ETE’s actions. OXER1 is highly expressed in inflammatory cells and many normal and cancer tissues and cells, including prostate and breast cancer, promoting cancer cell survival. In the present study we investigate the expression and role of OXER1 in WBCs, THP-1 monocytes, and THP-1 derived macrophages, as well as its possible role in the interaction between macrophages and cancer cells (DU-145 and T47D). We report that OXER1 is differentially expressed between WBCs and macrophages and that receptor expression is modified by LPS treatment. Our results show that testosterone and 5-oxo-ETE can act in an antagonistic way affecting Ca²⁺ movements, migration, and cytokines’ expression in immune-related cells, in a differentiation-dependent manner. Finally, we report that 5-oxo-ETE, through OXER1, can attract macrophages to the tumor site while tumor cells’ OXER1 activation in DU-145 prostate and T47D breast cancer cells, by macrophages, induces actin cytoskeletal changes and increases their migration. Full article