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.

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.

Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

A systematic review and meta-analysis of placebo effect in clinical trials on chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results. The purpose of this study was to evaluate the placebo effect on symptoms of CP/CPPS to improve future clinical trials. METHODS: A search at three databases (Scopus, MEDLINE, and Web of Science) was conducted to identify double-blind placebo-controlled clinical trials on the treatment of CP/CPPS published until April 2021. The primary outcome - National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score. SECONDARY OUTCOMES: Qmax, PVR, IPSS, and prostate volume. RESULTS: A total of 3502 studies were identified. Placebo arms of 42 articles (5512 patients, median 31 patients) were included in the systematic review. Systematic review identified positive changes in the primary endpoint, meta-analysis of 10 articles found that NIH-CPSI total score results were significantly influenced by placebo, mean difference -4.2 (95% confidence interval [CI]: -6.31, -2.09). Mean difference of NIH-CPSI pain domain was -2.31 (95% CI: -3.4, -1.21), urinary domain -1.12 (95% CI: -1.62, -0.62), quality of life domain -1.67 (95% CI: -2.38, -0.96); p < 0.001 for all. In case of the objective indicator - Qmax, there were three articles included in the meta-analysis. Qmax mean change from baseline was 0.68 (95% CI: -0.85, 2.22, p = 0.38). Systematic review showed no significant changes in pain, measured by VAS or other scores, IPSS and PVR. CONCLUSIONS: Placebo significantly affected the subjective parameters (NIH-CPSI) and limitedly affected various other measurements of pain (visual analog scale, McGill pain questionnaire). There was no long-term effect on IPSS and objective measurements (Qmax, PVR). This study can be used in further clinical trials to develop general rules of CPPS treatment assessment.

CXCR3 antagonist AMG487 ameliorates experimental autoimmune prostatitis by diminishing Th1 cell differentiation and inhibiting macrophage M1 phenotypic activation.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is an inflammatory immune disease that is characterized by infiltrating inflammatory cells in the prostate and pelvic or by perineal pain. Receptor CXCR3modulates immune and inflammatory responses; however, the effects of CXCR3 antagonist AMG487 in the context of CP/CPPS are unknown. Therefore, we investigated the effect of AMG487 in experimental autoimmune prostatitis (EAP) mice and explored the potential functional mechanisms. METHODS: The EAP model was induced by intradermally injecting a mixture of prostate antigens and complete Freund's adjuvant on Days 0 and 28. To evaluate the effect of AMG487 on EAP mice, treatment with AMG487 and vehicle solution was conducted for the indicated period. Then, procedures were performed, including behavioral test, to evaluate the pain response to stimulation before the mice were killed and a histological assessment to evaluate the inflammation after the mice were killed. Immunofluorescence, flow cytometry, and Western blot assay were used to analyze the functional phenotype and regulation mechanism of AMG487 on T helper type 1 (Th1) cells and macrophages. RESULTS: We found high expression of CXCR3 in human benign prostate tissues with inflammation and EAP mice. The elevated CXCR3 in prostate tissues correlates with the severity of inflammation. CXCR3 antagonist AMG487 treatment ameliorated the inflammatory changes and the pelvic pain of EAP mice. AMG487 inhibits Th1 cell differentiation through the IL-12/STAT4pathway and inhibits pro-inflammatory M1 macrophages through the lipopolysaccharide/NF-κB p65signaling. AMG487 could inhibit the secretion of inflammatory mediators in EAP mice. CONCLUSION: CXCR3 antagonist AMG487 could ameliorate the inflammatory changes and the pelvic pain of EAP mice by diminishing Th1 cell differentiation and inhibiting macrophage M1 phenotypic activation. Thus, the results imply that AMG487 has the potential as an effective therapeutic agent in the prevention and treatment of EAP.

Tadalafil monotherapy in management of chronic prostatitis/chronic pelvic pain syndrome: a randomized double-blind placebo controlled clinical trial.

PURPOSE: In this placebo-controlled trial, we aimed to evaluate the clinical results of using PDE-5 inhibitor, tadalafil 5 mg OD, for management of CP/CPPS. PATIENTS AND METHODS: 140 patients ≤ 45 years old with moderate/severe CP/CPPS associated with ED (IIEF-5 < 22) were randomly divided and received either tadalafil 5 mg OD (tadalafil-group) or placebo (control-group) for 6 weeks. Post-treatment CPSI scores were compared to baseline and to placebo. Clinically significant responders (≥ 25% reduction from baseline score) were calculated. Tadalafil-induced changes in IIE-5 were evaluated in correlation to that of CPSI scores. RESULTS: By the 6th week, 59 and 56 patients were available in both groups respectively. Compared to baseline, tadalafil-group patients showed significant improvement in total, pain, urinary and Qol domains of CPSI (19.1 ± 5.26, 10.42 ± 3.55, 4.2 ± 1.72 and 4.47 ± 1.64 vs. 24.21 ± 5.05, 12.14 ± 3.57, 6.08 ± 1.53 and 6.22 ± 1.76), p < 0.5. When compared to placebo, all 6th week CPSI domains scores, except for pain, were significantly better in tadalafil-group (p < 0.05). Post-treatment pain score didn't significantly differ between both groups (10.42 ± 3.55, vs. 11.71 ± 3.9, p > 0.05). Clinically significant responders were 30 patients (50.8%) in tadalafil-group vs. 3 patients (5.4%) in control. Tadalafil-induced changes in IIEF-5 score had weak but significant correlation to Qol domain (r = - 0.28, p < 0.05). CONCLUSION: Tadalafil 5 mg OD can significantly improve all CPSI domains as compared to baseline. Post-treatment CPSI scores, except for pain, were better than placebo. About 50.8% of patients can develop ≥ 25% reduction in their total CPSI scores after treatment. Apart from Qol domain, these changes are not significantly correlated to tadalafil-induced IIEF-5 scores changes.

Activated autophagy restored the impaired frequency and function of regulatory T cells in chronic prostatitis.

BACKGROUND: Chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS) is a disease with an unclear pathogenesis. Recent studies have reported that regulatory T (Treg) cells might be involved in the development of CP/CPPS. In this study we aimed to examine the functional role of Treg cells and explore the possible regulatory mechanism of Treg cells in CP/CPPS. METHODS: An experimental autoimmune prostatitis (EAP) mouse model was constructed; the numbers and functions of Treg cells in the EAP and control groups were tested. Then, cell differentiation experiments were conducted to evaluate the regulatory effect of autophagy on Treg cell differentiation. Furthermore, autologous CD4+ CD25- cells and CD4+ CD25+ cells from the two groups were magnetically sorted and cocultured to observe differences in cellular inhibitory functions. Finally, in an in vivo experiment, rapamycin was intraperitoneally injected into EAP mice for 4 weeks to observe the therapeutic effects. RESULTS: We found that the number and function of Treg cells in the EAP group were diminished compared to those in the control group. Meanwhile, the tolerance of pain in EAP mice had also decreased. Moreover, after using the autophagy activator rapamycin, the expression of the inflammatory cytokines interleukin-1ß was decreased and the pain symptoms were alleviated. A mechanistic study found that autophagy activation promoted the differentiation of Treg and increased the suppressive functions of Treg cells, along with the elevated expression of GATA-3 and cytotoxic T lymphocyte antigen 4 (CTLA-4). Furthermore, in vivo administration of the autophagy activator rapamycin had similar effects on recovering the frequency and function of Treg cells as well as the expression of GATA-3 and CTLA-4. CONCLUSION: The impaired frequency and function of Treg cells may contribute to the progression of CP/CPPS, and autophagy is a protective mechanism that promotes the differentiation of Treg cells and restores the suppressive functions of Treg cells. Autophagy may be a novel therapeutic option for patients with CP/CPPS.

Immunological alterations in patients with chronic prostatitis/chronic pelvic pain syndrome and experimental autoimmune prostatitis model: A systematic review and meta-analysis.

BACKGROUND: As one of the most common conditions in urological outpatients, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) puzzles many individuals because of its unclear etiology and lack of effective treatment. Recently, immunological alterations underpinning CP/CPPS have been extensively investigated. METHODS: The PubMed, Web of Science, Cochrane library, and EMBASE databases were used to search original articles on immune mediators in patients with CP/CPPS and in experimental autoimmune prostatitis (EAP) models through April 10, 2020. Standardized mean differences (SMD) were calculated to summarize the differences in immune mediator levels between groups. Funnel plot, Begg's funnel plot, Egger's regression test, and the sensitivity analysis were applied to determine and visualize the stability of our findings. RESULTS: A total of 34 original studies were included in the meta-analysis, including 24 studies on patients with CP/CPPS and 10 studies on EAP models. We found that TNF-α, IL-1ß, IL-6, and IL-8 were the four immune mediators that elevated in most of the samples derived from patients with CP/CPPS and the EAP models. The adjusted publication bias analysis indicated that publication bias was not existed, and the sensitivity analyses showed that the results were stable. CONCLUSIONS: Immune responses play significant roles during the pathogenesis of CP/CPPS by promoting intraprostatic inflammation. Our findings provide potential diagnostic and therapeutic targets for CP/CPPS patients.

The effectiveness of Hedyotis diffusa Willd extract in a mouse model of experimental autoimmune prostatitis.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frustrating and often debilitating disease. Current studies have shown that Traditional Chinese Medicine (TCM) can improve patients' quality of life and alleviate CP/CPPS symptoms. In this study, the efficacy of Hedyotis diffusa Willd aqueous extraction in experimental autoimmune prostatitis (EAP) mice models was revealed. The C57BL/6 mice were randomly assigned to three groups. Except for the control group, all other groups were subcutaneously injected with 0.2 ml emulsion of T2 peptide, on day 0 and day 14, for inducing EAP models. After the EAP modelling, oral saline was given to the model group, while the H. diffusa group was treated with aqueous extract of H. diffusa Willd. Micturition habits and withdrawal response frequencies were measured. Haematoxylin and eosin staining and immunohistochemistry were used to investigate inflammatory cell infiltration and TNF-α in the prostate tissue respectively. TNF-α levels in the serum were evaluated by ELISA. The H. diffusa Willd aqueous extraction considerably reduced the urine spots number and increased the pain threshold in H. diffusa group. H. diffusa group showed significantly reduced inflammatory lesion and inflammatory cell infiltration than the model group. The levels of TNF-α in H. diffusa group were considerably reduced.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters. METHODS: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers. RESULTS: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility. CONCLUSIONS: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.

Reliability and validity of the National Institutes of Health Chronic Prostatitis Symptom Index questionnaire in the Turkish Population

Background/aim: To develop the first Turkish version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH- CPSI) questionnaire and to investigate its validity and reliability in men with chronic prostatitis/chronic pelvic pain syndrome (CP/ CPPS) and healthy controls. Material and methods: A total of 204 patients, 116 CP/CPPS and a control group which consisted of 88 healthy individuals were included in this prospective study. The NIH-CPSI form was first translated into Turkish and later on back into English. Using the Turkish version of the NIH CPSI, 40 patients completed the same questionnaires twice at 2-week intervals for test-retest concordance. To evaluate internal consistency and test-retest reliability, Cronbach's alpha value, and the Spearman correlation test were utilized respectively. Results: Our findings demonstrated statistically significant differences in NIH-CPSI scores between the patients and control groups (P <0.001). Cronbach's alpha coefficient value of NIH-CPSI was 0.864. Reliability of test-retest was 0.909 (P <0.001). Additionally, the Spearman correlation test showed that the results obtained using the Turkish NIH-CPSI were significantly correlated. Conclusion: The first Turkish version of the NIH-CPSI was found to be a reliable and valid instrument for Turkish patients with chronic prostatitis in both clinical and research settings.

Morphological reseach on expression of inflammatory mediators in murine models of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) induced by T2 antigen.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common clinical syndrome with unknown aetiology. In this study, we used the T2 peptide in C57BL/6 (B6) mice and Sprague Dawley (SD) rats model during different stages. We sought to understand the role of CD4+ T cells and macrophages in CP/CPPS. A total of 16 B6 mice and 18 SD rats were divided into five groups: B6-naïve (n = 6), B6 model (n = 10), SD-naïve (n = 6), SD-45-day model (n = 6) and SD-56-day model (n = 6). The B6 model group was subcutaneously injected with 0.2 ml of (225µg/ml) T2 peptide on 0 and 14th day and was finally sacrificed on 28th day. The SD-45- and SD-56-day model groups were subcutaneously injected with 1ml of (50 µg/ml) T2 peptide on 0 and 14th day and were finally sacrificed on 45th and 56th day respectively. An equivalent volume of normal saline (NS) solution was injected to the naïve groups and analysed the pain and voiding behaviour. We have calculated the prostate index, H&E staining and immunofluorescence of CD4+ T cells and macrophages (CD68) in each group. T2 peptide immunization in B6 mice and SD rats caused severe prostatitis and cell infiltration, mainly composed of CD4+ T cells and macrophages. The SD-56-day model group showed more severe inflammatory cells infiltration than SD-45-day model group. Moreover, inflammatory cells infiltration and red secretions in B6 model were less than SD model. Expression of CD4+ T cells and macrophages was also consistent with H&E results. These results indicated that different stages of CP/CPPS, inflammatory response, and the inflammation of the rat were stronger than the mouse. Our study suggests that CD4+ T cells and macrophages are key factors in the development of CP/CPPS.

The effectiveness of long-needle acupuncture at acupoints BL30 and BL35 for CP/CPPS: a randomized controlled pilot study.

BACKGROUND: The chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the commonest chronic inflammatory diseases in adult men, for which acupuncture has been used to relieve related symptoms. The present study aimed to evaluate the therapeutic effect of the long-needle acupuncture on CP/CPPS. METHODS: A randomized traditional acupuncture-controlled single blind study was conducted on 77 patients who were randomized into long-needle acupuncture (LA) and traditional acupuncture (TA) groups. The patients received six sessions of acupuncture for 2 weeks and a follow-up was scheduled at week 24. The primary outcome was measured by the total National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) score at week 2. Four domains of the NIH-CPSI (urination, pain or discomfort, effects of symptoms, and quality of life) and the clinical efficacy score served as the secondary outcome. RESULTS: The total NIH-CPSI score at week 2 and week 24 was significantly improved in the LA group compared with the TA group. LA significantly improved urination, pain or discomfort, the effects of symptoms, and the quality of life at week 2 and week 24 and patients undergoing LA treatment had a higher clinical efficacy score. CONCLUSION: Needling at the BL30 and BL35 using LA benefits patients with CP/CPPS. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Register ( ChiCTR-ICR-15006138 ).

High glucose intake exacerbates experimental autoimmune prostatitis through mitochondrial reactive oxygen species-dependent TGF-ß activation-mediated Th17 differentiation.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common inflammatory immune disease of the urogenital system. High glucose intake is considered to be a potential promoter of autoimmune diseases. However, the influence of high glucose intake on CP/CPPS is unknown. This research aimed to explore the influences of high glucose intake on experimental autoimmune prostatitis (EAP), a valid animal model of CP/CPPS, and the underlying mechanism. NOD mice received 20% glucose water or normal water treatment during EAP induction. EAP severity and Th17 cell responses were evaluated. Then, we explored the effects of an IL-17A neutralizing antibody, an inhibitor of TGF-ß, the reactive oxygen species (ROS) inhibitor NAC, and the mitochondrial ROS (mtROS) antioxidant MitoQ on glucose-fed EAP mice. The results demonstrated that high glucose intake aggravated EAP severity and promoted Th17 cell generation, which could be ameliorated by the neutralization of IL-17A. In vitro experiments showed that high dextrose concentrations promoted Th17 cell differentiation through mtROS-dependent TGF-ß activation. Treatment with TGF-ß blockade, NAC, or MitoQ suppressed Th17 cell generation both in vivo and in vitro, resulting in the amelioration of EAP manifestations caused by high glucose intake. This study revealed that high glucose intake exacerbates EAP through mtROS-dependent TGF-ß activation-mediated Th17 differentiation. Our results may provide insights into the molecular mechanisms underlying the detrimental effects of an environmental factor, such as high glucose intake, on CP/CPPS.

Isoliquiritigenin reduces experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) lead to severe irritation and impaired sperm quality in males. However, current therapeutic options often fail to achieve satisfactory effects. Consequently, the investigation of novel treatment strategies or remedies holds substantial clinical importance. As a flavonoid monomer, isoliquiritigenin (ISL) has been shown to possess anti-inflammatory activity, especially in several chronic nonspecific-inflammatory conditions. Thus, an exploration of the possible anti-inflammatory effects of ISL on CP/CPPS, a chronic aseptic inflammation of the prostate, has significant potential. METHODS: An experimental autoimmune prostatitis (EAP) model was used for the evaluation of the anti-inflammatory effects of ISL. It was found that ISL treatment could reduce the secretion and invasion of pro-inflammatory cytokines in prostate tissue. In EAP mice, ISL treatment also reduced oxidative stress (OS) and activation of the NLRP3 inflammasome. In vitro, ISL upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited NLRP3 inflammasome activation in RAW264.7 macrophages exposed to lipopolysaccharide (LPS). RESULTS: Treatment with ISL treatment relieved prostate inflammation and pelvic pain in EAP mice. Both in vivo and in vitro, ISL treatment activated Nrf2/HO-1 signaling, which in turn inhibited oxidative stress and activation of the NLRP3 inflammasome. Blockade of Nrf2/HO-1 signaling abolished the inhibitory effects of ISL on oxidative stress and NLRP3 inflammasome activation. CONCLUSIONS: Isoliquiritigenin reduced experimental autoimmune prostatitis by facilitating Nrf2 activation and suppressing the NLRP3 inflammasome pathway.

Trends in experimental autoimmune prostatitis: insights into pathogenesis, therapeutic strategies, and redefinition.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPSS) is a debilitating condition characterized by prostate inflammation, pain and urinary symptoms. The immune system's response to self-antigens is a contributing factor to CP/CPSS. In this review, we examine the use of experimental autoimmune prostatitis (EAP) in rodents to model salient features of autoimmune mediated CP/CPSS. By exploring etiological factors, immunological mechanisms, and emerging therapeutic strategies, our aim is to enhance our understanding of CP/CPSS pathogenesis and promote the development of strategies to test innovative interventions using the EAP pre-clinical model.

Clinical efficacy of magnetic vibration magnetoelectric therapy in the treatment of chronic prostatitischronic pelvic pain syndrome.

BACKGROUND: The prominent symptoms of chronic pelvic pain syndrome (CPPS) are urogenital pain, lower urinary tract symptoms, psychological problems, and sexual dysfunction. Traditional pharmacological treatments have poor efficacy and more untoward reaction and complications. Magnetic vibration magnetoelectric therapy is a non-invasive form of physiotherapy. Nevertheless, its effectiveness in improving urinary discomfort and relieving pain in patients requires further exploration. AIM: To investigate the clinical efficacy of the magnetic vibration magnetoelectric therapy instrument in the treatment of chronic prostatitis (CP)/ CPPS. METHODS: Seventy patients with CP/CPPS were collected from the outpatient clinic and ward of the Department of Male Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, and were treated with magnetic vibration magnetoelectric therapy once a day for a period of 14 d. National Institutes of health-chronic prostatitis symptom index (NIH-CPSI), international index of erectile function 5 (IIEF-5), premature ejaculation diagnostic tool (PEDT), generalized anxiety disorder (GAD), patient health questionnaire, the pain catastrophizing scale (PCS) and traditional Chinese medicine syndrome (TCMS) scores were performed before and after treatment. RESULTS: The total effective rate of treatment was 58.5%, and the total NIH-CPSI score, pain symptoms, voiding symptoms, quality of life, IIEF-5, PEDT, GAD, PCS and TCMS scores all decreased significantly (P < 0.05). CONCLUSION: Magnetic vibration magnetotherapy is effective in improving urinary discomfort, relieving pain, improving quality of life, improving sexual dysfunction and relieving negative emotions such as anxiety in patients with CP/CPPS.

Effect of acupuncture on quality of life in patients with chronic prostatitis/chronic pelvic pain syndrome: a randomized controlled trial. / é’ˆåˆºæ²»ç–—å¯¹æ ¢æ€§å‰åˆ—è ºç‚Ž/æ ¢æ€§ç›†è ”ç–¼ç—›ç»¼åˆå¾æ‚£è€ ç”Ÿæ´»è´¨é‡çš„å½±å“ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the effect and safety of acupuncture on quality of life, pain, and prostate symptoms in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: Seventy patients with CP/CPPS were randomly divided into an acupuncture group (35 cases, 1 case was eliminated) and a sham acupuncture group (35 cases, 3 cases dropped out). The patients in the acupuncture group were treated with routine acupuncture at bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6), while the patients in the sham acupuncture group were treated with shallow needling at non-meridian and non-acupoint points beside bilateral Zhongliao (BL 33), Huiyang (BL 35), Shenshu (BL 23) and Sanyinjiao (SP 6),without manipulation to induce arrival of qi (deqi). Both groups retained the needles for 30 min, with one session every other day, three times a week, for a total of 8 weeks (24 sessions). Before and after treatment, and at the follow-up of 24 weeks after treatment completion, the scores of MOS 36-item short-form health survey (SF-36, including 8 dimensions of physical function [PF], role physical function [RP], bodily pain [BP], general health status [GH], vitality [VT], social function [SF], role emotional [RE], and mental health [MH], which can be summarized as physical component summary [PCS] and mental component summary [MCS]), pelvic pain visual analogue scale (VAS), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and international prostate symptom score (IPSS) were evaluated, and safety of both groups was assessed. RESULTS: After treatment and at the follow-up, the scores of each dimension and PCS, MCS scores of SF-36 in the acupuncture group were higher than those before treatment (P<0.05, P<0.01); compared before treatment, the RP, BP, and SF scores and PCS score in the sham acupuncture group were increased after treatment (P<0.05, P<0.01). After treatment, the acupuncture group had higher scores in RP, BP, GH, MH and PCS, MCS than those in the sham acupuncture group (P<0.05, P<0.01); at the follow-up, except for PF and RE dimensions, the scores in each dimension and PCS, MCS scores in the acupuncture group were higher than those in the sham acupuncture group (P<0.05, P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those before treatment (P<0.01); in the sham acupuncture group, pelvic pain VAS, NIH-CPSI scores were lower after treatment, and NIH-CPSI score at the follow-up was lower compared with those before treatment (P<0.01). After treatment and at the follow-up, pelvic pain VAS, NIH-CPSI, IPSS scores in the acupuncture group were lower than those in the sham acupuncture group (P<0.01, P<0.05). No significant adverse reactions were observed in both groups, and the incidence rates of adverse reactions had no significant difference (P>0.05). CONCLUSIONS: Acupuncture could effectively improve the quality of life, reduce pain levels, alleviate prostate symptoms, and shows favorable long-term efficacy in patients with CP/CPPS.

Traditional Chinese herbal medicine retention enema combined with perineal massage (THREM): a promising therapeutic strategy for refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.