Unraveling CCL20's role by regulating Th17 cell chemotaxis in experimental autoimmune prostatitis.

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS), a prevalent urological ailment, exerts a profound influence upon the well-being of the males. Autoimmunity driven by Th17 cells has been postulated as a potential factor in CP/CPPS pathogenesis. Nonetheless, elucidating the precise mechanisms governing Th17 cell recruitment to the prostate, triggering inflammation, remained an urgent inquiry. This study illuminated that CCL20 played a pivotal role in attracting Th17 cells to the prostate, thereby contributing to prostatitis development. Furthermore, it identified prostate stromal cells and immune cells as likely sources of CCL20. Additionally, this research unveiled that IL-17A, released by Th17 cells, could stimulate macrophages to produce CCL20 through the NF-κB/MAPK/PI3K pathway. The interplay between IL-17A and CCL20 establishes a positive feedback loop, which might serve as a critical mechanism underpinning the development of chronic prostatitis, thus adding complexity to its treatment challenges.

4-Octyl itaconate alleviates experimental autoimmune prostatitis by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation. METHODS: Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups. RESULTS: IHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1ß, IL-6, and TNF-α), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP. CONCLUSIONS: The present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment.

Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay. RESULTS: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway. CONCLUSIONS: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.

Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms.

BACKGROUND: Gut microbiome is a community of microorganisms that lives in the human intestine and exerts various functions on the host, including metabolic, immunoregulatory, and control over cell proliferation. Gut microbiome alterations have been associated with various pathological conditions, such as diabetes mellitus, obesity, and cardiovascular diseases. Gut-prostate axis is explained by the association between gut microbiome quantitative and functional alterations along with increased intestinal epithelial permeability with prostatediseases. However, the pathophysiological mechanisms and clinical importance of this association are not completely clarified yet. METHODS: We conducted a narrative review of the most relevant articles in the Medline (US National Library of Medicine, Bethesda, MD, USA), Scopus (Elsevier, Amsterdam, The Netherlands) and Web of Science Core Collection (Thomson Reuters, Toronto, ON, Canada) databases. No chronological restrictions were applied, and the most related papers published until December 2023 were included. RESULTS: Gut microbiota (GM) and its metabolites are capable of modifying host androgen level, as well as prostate cancer (PCa) therapy response. Moreover, patients with inflammatory bowel disease have higher rates of prostatitis-like symptoms and a potential risk of developing PCa. CONCLUSIONS: There is evidence that interventions on the GM and its metabolites have a high potential to serve as diagnostic and therapeutic tools for prostate diseases, including PCa.

Assessing the causal relationship between immune cells and prostatitis: evidence from bidirectional mendelian randomization analysis.

Prostatitis represents a common disease of the male genitourinary system, significantly impacting the physical and mental health of male patients. While numerous studies have suggested a potential link between immune cell activity and prostatitis, the exact causal role of immune cells in prostatitis remains uncertain. This study aims to explore the causal relationship between immune cell characteristics and prostatitis using a bidirectional Mendelian randomization approach. This study utilizes data from the public GWAS database and employs bidirectional Mendelian randomization analysis to investigate the causal relationship between immune cells and prostatitis. The causal relationship between 731 immune cell features and prostatitis was primarily investigated through inverse variance weighting (IVW), complemented by MR-Egger regression, a simple model, the weighted median method, and a weighted model. Ultimately, the results underwent sensitivity analysis to assess the heterogeneity, horizontal pleiotropy, and stability of Single Nucleotide Polymorphisms (SNPs) in immune cells and prostatitis. MR analysis revealed 17 immune cells exhibiting significant causal effects on prostatitis. In contrast, findings from reverse MR indicated a significant causal relationship between prostatitis and 13 immune cells. Our study utilizes bidirectional Mendelian Randomization to establish causal relationships between specific immune cell phenotypes and prostatitis, highlighting the reciprocal influence between immune system behavior and the disease. Our findings suggest targeted therapeutic approaches and the importance of including diverse populations for broader validation and personalized treatment strategies.

Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

PURPOSE: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. MATERIALS AND METHODS: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. RESULTS: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. CONCLUSIONS: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

A holistic biopsychosocial management approach for cis-gender males with chronic pelvic pain syndrome attending sexual health services: a retrospective case review.

OBJECTIVES: Chronic pelvic pain syndrome (CPPS) in men is a condition associated with significant morbidity which is typically managed in sexual health services. We introduced a modified biopsychosocial approach for managing CPPS in men, reducing use of antibiotics and evaluated its application in a retrospective case review. METHODS: Patients attended for a full consultation covering symptomology, onset and social history. Examination included urethral smear and assessment of pelvic floor tension and pain. A focus on pelvic floor relaxation was the mainstay of management with pelvic floor physiotherapy if required. Prescribing of antibiotics being discontinued if no evidence of urethritis at first consultation. The main outcome was change in the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score (which patients completed at each attendance); significant clinical improvement was defined as a NIH-CPSI score reduction of >25% and/or ≥6 points. RESULTS: Among 77 consecutive patients diagnosed with CPPS between April 2017 and December 2018, the mean NIH-CPSI score at the initial visit was 24.1 (11-42). Antibiotics were prescribed to 38/77 (49.4%) and alpha-blockers to 58/77 (75.3%). Overall, 50 (64.9%) patients with a mean initial NIH-CPSI score of 25.4 (11-42) re-attended a CPPS clinic. Among these, the average NIH-CPSI score at the final CPPS clinic appointment declined to 15.9 (0-39) (p<0.001); 34/50 (68%) men experienced significant clinical improvement. Men who attended only one CPPS clinic compared with those who reattended had a shorter duration of symptoms (18 (1-60) vs 36 (1-240) months; p=0.038), a lower initial NIH-CPSI score (21.7 (11-34) vs 25.4 (11-44); p=0.021), but had attended a similar number of clinics prior to referral (2.9 (0-6) vs 3.2 (0-8); p=0.62). CONCLUSIONS: The biopsychosocial approach significantly reduced the NIH-CPSI score in those who re-attended, with 68% of patients having a significant clinical improvement. The first follow-up consultation at 6 weeks is now undertaken by telephone for many patients, if clinically appropriate.

Causal relationship between prostatic diseases and prostate cancer: a mendelian randomization study.

BACKGROUND: Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear. METHODS: We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10-6). The accuracy of the results was confirmed using sensitivity analyses. RESULTS: MR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098-0.281, P = 5.079 × 10- 5) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable. CONCLUSIONS: This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.

Dual deficiency of melatonin and dihydrotestosterone promotes stromal cell damage and mediates prostatitis via the cGAS-STING pathway in sleep-deprived mice.

PURPOSE: Prostatitis is a highly prevalent condition that seriously affects men's physical and mental health. Although epidemiological investigations have provided evidence of a correlation between insufficient sleep and prostatitis, the pathogenesis of prostatitis remains unclear. We sought to identify the underlying mechanism involved and identify a promising therapeutic target. METHODS: Sleep deprivation (SD) was utilized to establish a mouse model of insufficient sleep in a special device. Prostatitis was observed at different time points post-SD. The degree of prostatitis was evaluated by pathological section and behavioural tests. Using immunofluorescence, western blot, and proteomic analyses, the underlying mechanism of SD-related prostatitis was investigated, and the development and therapeutic target of prostatitis were elucidated. RESULTS: SD, as an initial pathological trigger, resulted in a reduction in dihydrotestosterone and melatonin levels. Proteomic analysis revealed that the cGAS-STING pathway may play a significant role in inducing prostatitis. The subsequent results illustrated that the dual reduction in dihydrotestosterone and melatonin led to an accumulation of reactive oxygen species and the release of mitochondrial DNA (mt-DNA). The accumulation of mt-DNA activated the cGAS-STING pathway, which recruited inflammatory cells into the prostatic stroma through the secretion of interferon-ß. Consequently, an inflammatory microenvironment was formed, ultimately promoting the development of prostatitis. Notably, mice with SD-induced prostatitis gradually recovered to a normal state within 7 days of recovery sleep. However, after being subjected to SD again, these mice tended to have a more pronounced manifestation of prostatitis within a shorter timeframe, which suggested that prostatitis is prone to relapse. CONCLUSIONS: The cGAS-STING pathway activated by dual deficiency of dihydrotestosterone and melatonin plays a comprehensive inflammatory role in SD-related prostatitis. This research provides valuable insights into the pathogenesis, therapeutic targets, and prevention strategies of prostatitis.

Factors related to acupuncture response in patients with chronic prostatitis/chronic pelvic pain syndrome: secondary analysis of a randomized controlled trial.

PURPOSE: Acupuncture has been recommended as an effective therapy to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We conducted this secondary analysis to explore the factors that may influence the response of patients with CP/CPPS to acupuncture. METHODS: This secondary analysis was based on a randomized controlled trial demonstrating the efficacy of acupuncture among patients with CP/CPPS. Responder is defined as a patient with a decrease of ≥ 6 points in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score from baseline at the 32 week. 206 patients who received acupuncture treatment and completed 32-week follow-up were included in this secondary analysis. Descriptive statistics were used to describe the demographic and clinical characteristics of both responders and non-responders in acupuncture group. Logistic regression analysis with bootstrapping was made to identify potential factors that contributed to the effectiveness of acupuncture for treating CP/CPPS. Responders and non-responders were listed as dependent variables. RESULTS: In this study, 130 (63.11%) patients were assessed as responders. The results showed that men with non-sedentariness (OR 4.170 [95%CI 1.837 to 9.463; P = 0.001]), non-smoking habit (OR 2.824 [95%CI 1.453 to 5.487; P = 0.002]), without comorbidity (OR 8.788 [95%CI 1.912 to 40.295; P = 0.005]), and severe NIH-CPSI total score (OR 0.227 [95%CI 0.114 to 0.450; P < 0.0001]) benefited more from acupuncture intervention. CONCLUSION: CP/CPPS patients who are active, non-smokers, without comorbidity, and had severe symptoms may be more likely to respond to acupuncture.

Association between chronic prostatitis and the subsequent benign prostatic hyperplasia: a population-based national cohort study.

PURPOSE: To explore the association between chronic prostatitis (CP) and the subsequent development of benign prostatic hyperplasia (BPH). METHODS: Data analyzed were medical claims of Taiwan's National Health Insurance program. From 2010 to 2017, 3571 patients ≧20 years with CP diagnosed by certified urologists were enrolled. Patients with past BPH diagnosis and diagnosis of prostate cancer, inguinal hernia, interstitial cystitis, and urethritis in the past and within one year after the first CP diagnosis were excluded. Age-matched controls were randomly selected from all non-CP individuals of the same exclusion criteria in the study period with a CP/non-CP ratio of 1:4. The follow-up was made from the first CP diagnosis to death or the end of 2018. The endpoint was the newly diagnosed BPH. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of BPH in association with CP. RESULTS: Over a maximum of 8 years of follow-up, 287 (8.03%) and 258 (0.43%) BPH events were noted for the CP and non-CP group, respectively, representing a covariate adjusted HR (aHR) of 4.30 (95% CI, 3.61-5.13). Younger patients tended to suffer from higher aHRs, especially those aged 20-39 years (aHR: 11.45, 95% CI, 5.12-25.64). CONCLUSION: The Taiwan national health database indicated that CP patients had a significantly higher risk of developing BPH later than non-CP patients. Interestingly, the younger the CP is diagnosed (under 40), the greater the risk.

Extracorporeal shockwave therapy in treatment of chronic prostatitis/chronic pelvic pain syndrome: Systematic review and meta-analyses.

AIMS: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) prevalence varies from 8.4% to 25% of the male population and is associated with diminished health-related quality of life. Managing CP/CPPS remains challenging and there is not any common option to treat all patients effectively because of the complex disease nature. The currently available data for the extracorporeal shockwave therapy (eSWT) effect on pain relief and well-being were analyzed in the present study. METHODS: We adhered to PRISMA 2022 guidelines for reporting the quantitative and qualitative data synthesis. A literature search was conducted in March 2023 using PubMed/Medline, Scopus, and Google Scholar. Randomized prospective studies of eSWT alone or eSWT plus conventional medicinal treatment were included. The risk of bias was estimated using the RoB 2.0. Primary outcomes were self-reported scores, including the NIH-CPSI questionnaire and VAS, at 1 month or 2, 3, and 6, months follow-up. RESULTS: The CP/CPPS patients who receive eSWT have more pronounced pain relief and improvement of other subjective NIH-CPSI scores compared with control groups that received placebo or medication therapy. The effect of eSWT seems to be long-lasting and was confirmed in the 6-month follow-up (p < 0.01). CONCLUSIONS: Based on the meta-analysis of accessible studies, we receive the equivalence eSWT applicability for the CP/CPPS treatment and can be offered to patients because of its noninvasiveness, high level of safety, and successful clinical results demonstrated in this analysis.

Water-avoidance stress aggravates prostatic inflammation in a murine model of chronic prostatitis.

OBJECTIVES: To date, few studies have considered the influence of psychological factors on chronic prostatitis (PRO) models. Here, we aimed to refine a murine PRO model combining chemically induced prostatitis with psychological stress. METHODS: A total of 40 mice were randomly divided into four groups: normal control (NC) group, PRO group, water avoidance stress (WAS) group, and PRO + WAS group. Ten mice were assigned to each group: five for cystometrograms (CMGs) and five for von Frey testing and histological analysis. PRO was induced through a prostatic injection of 10% paraformaldehyde. The WAS mice were placed on the middle platform for 1 h per day for 10 consecutive days. RESULTS: The results of the von Frey test demonstrated that both WAS and PRO induced bladder hyperalgesia in mice, and the WAS + PRO group showed significant pelvic pain symptoms either. The CMG results suggested that the PRO group, the WAS group, and the PRO + WAS group all exhibited bladder overactivity, presented as a shortened micturition interval and decreased threshold pressure evoking bladder contraction. The symptoms of the PRO group and the PRO + WAS group were more severe than those of the WAS group. The tissue staining results indicated that WAS itself caused only mild prostatic inflammation but could significantly aggravate chemical-induced prostatic inflammation, as well as the total number of mast cells and proportion of activated mast cells. CONCLUSIONS: Our refined murine PRO model could manifest persistent bladder overactivity, pelvic hyperalgesia and prostatic inflammation. WAS could induce mild prostatic inflammation and aggravate primary prostatic inflammation.

Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

PURPOSE: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. MATERIALS AND METHODS: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site. RESULTS: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations. CONCLUSIONS: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.

A systematic and comprehensive review of the role of microbiota in urinary chronic pelvic pain syndrome.

BACKGROUND: Many genitourinary tract disorders could be attributed partly to the microbiota. This study sought to conduct a systematic review of the role of the microbiota in urinary chronic pelvic pain syndrome (UCPPS). METHODS: We searched Embase, Scopus, Web of Science, and PubMed with no time, language, or study type restrictions until December 1, 2023. The JBI Appraisal Tool was used to assess the quality of the studies. Study selection followed the PRISMA statement. Studies addressing microbiome variations among patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and a control group were considered eligible. RESULTS: A total of 21 studies (1 UCPPS, 12 IC/BPS, and 8 CP/CPPS) comprising 1125 patients were enrolled in our final data synthesis. It has been shown that the reduced diversity and discrepant composition of the gut microbiota may partly be attributed to the UCPPS pathogenesis. In terms of urine microbiota, some operational taxonomic units were shown to be elevated, while others became less abundant. Furthermore, various bacteria and fungi are linked to specific clinical features. Few investigations denied UCPPS as a dysbiotic condition. CONCLUSIONS: Urinary and intestinal microbiota appear to be linked with UCPPS, comprising IC/BPS and CP/CPPS. However, given the substantial disparity of published studies, a battery of prospective trials is required to corroborate these findings.

Thermosensitive hydrogel with emodin-loaded triple-targeted nanoparticles for a rectal drug delivery system in the treatment of chronic non-bacterial prostatitis.

BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.

Hypertension and urologic chronic pelvic pain syndrome: An analysis of MAPP-I data.

BACKGROUND: Urologic chronic pelvic pain syndrome (UCPPS), which includes interstitial cystitis/bladder pain syndrome (IC/BPS) and chronic prostatitis (CP/CPPS), is associated with increased voiding frequency, nocturia, and chronic pelvic pain. The cause of these diseases is unknown and likely involves many different mechanisms. Dysregulated renin-angiotensin-aldosterone-system (RAAS) signaling is a potential pathologic mechanism for IC/BPS and CP/CPPS. Many angiotensin receptor downstream signaling factors, including oxidative stress, fibrosis, mast cell recruitment, and increased inflammatory mediators, are present in the bladders of IC/BPS patients and prostates of CP/CPPS patients. Therefore, we aimed to test the hypothesis that UCPPS patients have dysregulated angiotensin signaling, resulting in increased hypertension compared to controls. Secondly, we evaluated symptom severity in patients with and without hypertension and antihypertensive medication use. METHODS: Data from UCPPS patients (n = 424), fibromyalgia or irritable bowel syndrome (positive controls, n = 200), and healthy controls (n = 415) were obtained from the NIDDK Multidisciplinary Approach to the Study of Chronic Pelvic Pain I (MAPP-I). Diagnosis of hypertension, current antihypertensive medications, pain severity, and urinary symptom severity were analyzed using chi-square test and t-test. RESULTS: The combination of diagnosis and antihypertensive medications use was highest in the UCPPS group (n = 74, 18%), followed by positive (n = 34, 17%) and healthy controls (n = 48, 12%, p = 0.04). There were no differences in symptom severity based on hypertension in UCPPS and CP/CPPS; however, IC/BPS had worse ICSI (p = 0.031), AUA-SI (p = 0.04), and BPI pain severity (0.02). Patients (n = 7) with a hypertension diagnosis not on antihypertensive medications reported the greatest severity of pain and urinary symptoms. CONCLUSION: This pattern of findings suggests that there may be a relationship between hypertension and UCPPS. Treating hypertension among these patients may result in reduced pain and symptom severity. Further investigation on the relationship between hypertension, antihypertensive medication use, and UCPPS and the role of angiotensin signaling in UCPPS conditions is needed.

Ursolic acid alleviates chronic prostatitis via regulating NLRP3 inflammasome-mediated Caspase-1/GSDMD pyroptosis pathway.

Ursolic acid (UA) is a naturally occurring pentacyclic triterpenoid widely found in fruits and vegetables. It has been reported that UA has anti-inflammatory effects. However, its efficacy and mechanism of action in the treatment of chronic prostatitis (CP) remain unclear. This study aimed to investigate the efficacy of UA treatment in CP and further explore the underlying mechanism. CP rat and pyroptosis cell models were established in vivo and in vitro, respectively. The efficacy of UA in inhibiting CP was evaluated via haematoxylin-eosin (HE) staining and measurement of inflammatory cytokines. RNA sequencing and molecular docking were used to predict the therapeutic targets of UA in CP. The expression of pyroptosis-related proteins was examined using various techniques, including immunohistochemistry, immunofluorescence, and flow cytometry. UA significantly ameliorated pathological damage and reduced the levels of proinflammatory cytokines in the CP model rats. RNA sequencing analysis and molecular docking suggested that NLRP3, Caspase-1, and GSDMD may be key targets. We also found that UA decreased ROS levels, alleviated oxidative stress, and inhibited p-NF-κB protein expression both in vivo and in vitro. UA improved pyroptosis morphology as indicated by electron microscope and inhibited the expression of the pyroptosis-related proteins NLRP3, Caspase-1, ASC, and GSDMD, reversed the levels of IL-1ß, IL-18, and lactate dehydrogenase in vivo and in vitro. UA can mitigate CP by regulating the NLRP3 inflammasome-mediated Caspase-1/GSDMD pathway. Therefore, UA may be a potential for the treatment of CP.

The harmful effects of overlooking acute bacterial prostatitis.

Prostatitis is a major urological disease affecting 25%-50% of men over their lifetime. However, prostatitis is often overlooked in nonurologic departments due to its sometimes indeterminate symptoms. In this review, we describe how to recognize and treat acute bacterial prostatitis, which manifests as a clinical problem in other departments as well as urology, to help prevent this disease from being overlooked. There are several possible negative effects of not recognizing acute bacterial prostatitis (ABP). First, initial treatment can fail. In the hyperacute phase, common antibiotics are often effective, but in rare cases, such antibiotics may not be effective. In addition, once ABP progresses to form a prostate abscess, potentially avoidable surgical interventions are often needed. A second issue is the transition to chronic prostatitis. If chronic bacterial prostatitis progresses, treatment requires long-term antibiotic administration and the response rate is not high. Some patients may have to deal with urinary tract infections for the rest of their lives. Finally, there is the problem of overlooking the underlying disease. ABP is rare in healthy adult men without underlying disease, including sexually transmitted diseases as well as benign prostatic hyperplasia, urinary stones, and malignant tumors, and may not be obvious. When examining patients with fever of unknown origin, it is necessary to exclude not only infectious diseases but also collagen diseases and malignant tumors. If there are any doubts, we recommend a rectal exam and consultation with a urologist.

Hedyotis diffusa Willd inhibits inflammation and oxidative stress to protect against chronic prostatitis via the NRF2/ARE signaling pathway.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common and serious disease with unclear pathogenesis and recurrent symptoms. Hedyotis diffusa Willd (HDW) has been recognized for its potential in managing various chronic inflammatory diseases. This research aimed to interrogate the mechanism of HDW in treating CP/CPPS. Complete Freund Adjuvant (CFA) and LPS were utilized to establish the rat and cell models of CP/CPPS. Results showed that HDW decreased levels of inflammation-related factors in CP rat prostate tissue and LPS-elicited RWPE-1 cell injury model. Moreover, HDW administration impaired oxidative stress in the prostate and RWPE-1 cells. In addition, HDW treatment activated the NRF2/ARE signaling in rat prostate tissue and cell models. Interestingly, NRF2/ARE pathway inhibitor ML385 reversed the inhibition effects of cell apoptosis, inflammation, and oxidative stress triggered by HDW. In summary, HDW alleviated inflammation and oxidative stress by activating NRF2/ARE signaling in CP/CPPS rat model and human prostate epithelial cell injury model.