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Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process., Method: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice., Results: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet., Conclusion: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the mechanism of the CXCL10/CXCR3 axis regulating Th1 cell differentiation and migration through the PI3K/AKT pathway in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS)., Methods: Experimental autoimmune prostatitis (EAP) model, a well-described and validated animal model of CP/CPPS, was used in our study. After treatment with CXCL10, the severity of EAP and Th1 cell proportion were respectively measured by HE stains, immunohistochemistry, and flow cytometry. Then, the protein expression of the PI3K/AKT pathway in CXCL10/CXCR3-regulated Th1 cell differentiation and migration was evaluated by western blotting. Additionally, by the CXCR3 antagonist AMG487 and the PI3K inhibitor LY294002 applications, the effects of CXCL10/CXCR3 through PI3K/AKT pathway on the Th1 cell differentiation and migration were further assessed., Results: The EAP model was successfully built. CXCL10 increased the proportion of Th1 cells in EAP mice, accompanied by upregulation of the PI3K/AKT pathway. Additionally, the PI3K/AKT pathway was found to be involved in CXCL10/CXCR3 axis-mediated Th1 cell differentiation and migration., Conclusions: Our investigations indicate that the CXCL10/CXCR3 axis regulates Th1 cell differentiation and migration in EAP through the PI3K/AKT pathway, which provides a new perspective on the immunological mechanisms of CP/CPPS., (© 2023 American Society of Andrology and European Academy of Andrology.)

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., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

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-β, 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-β activation. Treatment with TGF-β 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-β 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. Interleukin-17 (IL-17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS are not clear. We confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL-17-neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti-Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL-17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration., (© 2022 Wiley-VCH GmbH.)

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a very common urological disorder and has been gradually regarded as an immune-mediated disease. Multiple studies have indicated that the gut microflora plays a pivotal part in immune homeostasis and autoimmune disorder development. However, whether the gut microflora affects the CP/CPPS, and the underlying mechanism behind them remain unclear. Here, we built an experimental autoimmune prostatitis (EAP) mouse model by subcutaneous immunity and identified that its Th17/Treg frequency was imbalanced. Using fecal 16s rRNA sequencing and untargeted/targeted metabolomics, we discovered that the diversity and relative abundance of gut microflora and their metabolites were obviously different between the control and the EAP group. Propionic acid, a kind of short-chain fatty acid (SCFA), was decreased in EAP mice compared to that in controls, and supplementation with propionic acid reduced susceptibility to EAP and corrected the imbalance of Th17/Treg cell differentiation in vivo and in vitro . Furthermore, SCFA receptor G-protein-coupled receptor 43 and intracellular histone deacetylase 6 regulated by propionic acid in Th17 and Treg cells were also evaluated. Lastly, we observed that fecal transplantation from EAP mice induced the decrease of Treg cell frequency in recipient mice. Our data showed that gut dysbiosis contributed to a Th17/Treg differentiation imbalance in EAP via the decrease of metabolite propionic acid and provided valuable immunological groundwork for further intervention in immunologic derangement of CP/CPPS by targeting propionic acid., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Yue, Niu, Liu, Zhang, Chen, Chen, Guan, Hua, Li, Chen, Zhang and Liang.)

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male genitourinary system disease. As a neuroendocrine hormone, melatonin possesses a variety of biological functions, among which its anti-inflammatory effects have recently drawn substantial attention. The purpose of the current research was to study the effect of melatonin on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP)., Methods: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. On Day 42, hematoxylin-eosin staining was used to evaluate the histological appearance of prostate tissues. Chronic pelvic pain development was assessed by suprapubic allodynia. The levels of inflammation-related cytokines, such as interferon-γ, interleukin (IL)-17, and IL-1β, were detected by enzyme-linked immunosorbent assay. Then, we explored the anti-inflammatory effects of melatonin on CP/CPPS by Western blotting and immunohistochemical staining, by measuring the expression of silent information regulator 1 (Sirt1) and NLRP3 inflammasome-related proteins in EAP mice., Results: The EAP model mice exhibited severe diffuse leukocyte infiltration and significantly increased pelvic pain compared to the control mice. In the melatonin treatment group, the histological appearance of the prostate tissues, pelvic pain development, and the levels of proinflammatory cytokines were significantly alleviated compared to the EAP + dimethyl sulfoxide group. Furthermore, we found that the protective effects of melatonin were achieved through activation of the Sirt1 pathway and downregulation of the NLRP3 inflammasome., Conclusions: The results indicated that melatonin could attenuate prostate inflammation and pelvic pain by inhibiting the NLRP3 inflammasomes signaling pathway through the activation of Sirt1 in mice with EAP, and these efforts should provide a promising therapeutic strategy for CP/CPPS., (© 2021 Wiley Periodicals LLC.)

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease in males. Eriocalyxin B (EriB), a natural diterpenoid purified from Isodon eriocalyx var. laxiflora, was previously reported to have antitumor effects via multiple immune-related pathways. In this study, we investigated the effect of EriB on CP/CPPS using a mouse model of experimental autoimmune prostatitis (EAP) and explored its potential mechanisms., Methods: The EAP model was established in nonobese diabetic mice by intradermal injecting a mixture of prostate antigens and Complete Freund's Adjuvant on days 0 and 28. Then, EAP mice received daily intraperitoneal injections of EriB (5 or 10 mg/kg/d) for 14 days, from days 28 to 42 (EAP+EriB5 or EAP+EriB10 groups). The histopathological appearance of the prostate tissues was evaluated. Chronic pelvic pain development was assessed by cutaneous allodynia. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay tests. We then explored anti-inflammatory potential mechanisms of EriB by studying the effects of PI3K inhibitor wortmannin (EAP+EriB10+Wort group) and NF-κB inhibitor SC75741 (EAP+EriB10+SC group) on prostate inflammation and pelvic pain using this model., Results: Histological analyses revealed significant prostate inflammation in EAP mice compared with control mice. Significantly increased pelvic pain was detected in EAP mice (P < .05). Compared with the EAP+Veh group, chronic pain development, histological appearance, and cytokine levels demonstrated that EriB could alleviate the severity of EAP in a dose-dependent manner though upregulation of the PI3K/Akt/mTOR pathway and downregulation of the NF-κB pathway. Further mechanism research demonstrated that the PI3K/AKT/mTOR pathway could be blocked by wortmannin, but was not affected by SC75741. In addition, the NF-κB pathway could be further inhibited by SC75741 compared with the EAP+EriB10+Veh group. However, wortmannin could reactivate the NF-κB pathway, indicating that the PI3K/AKT/mTOR pathway negatively regulates the NF-κB pathway during EriB treatment., Conclusions: The results of the present study suggested that EriB could alleviate the severity of prostatic inflammation and pelvic pain in an EAP mouse model. These findings may broaden the value of EriB as a promising candidate for the treatment of CP/CPPS., (© 2020 Wiley Periodicals LLC.)

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is a complicated syndrome characterized by genitourinary pain in the absence of bacterial infection. Th17 cell-driven autoimmunity has been proposed as a cause of CP/CPPS. However, the factors that promote Th17-driven autoimmunity in experimental autoimmune prostatitis (EAP) and the molecular mechanisms are still largely unknown. Here, we showed that Th17 cells were excessively activated, and blockade of IL-17A could effectively ameliorate various symptoms in EAP. Furthermore, we revealed that calcium/calmodulin-dependent kinase Ⅳ (CaMK4), especially Thr 196 p-CaMK4 was increased in the Th17 cells of the EAP group, which were activated by intracellular cytosolic Ca 2+ . Pharmacologic and genetic inhibition of CaMK4 decreased the proportion of Th17 cells, and the protein and mRNA level of IL-17A, IL-22, and RORγt. The phosphorylation of CaMK4 was dependent on the increase in intracellular cytosolic Ca 2+ concentration in Th17 cells. A mechanistic study demonstrated that inhibition of CaMK4 reduced IL-17A production by decreasing the phosphorylation of Akt-mTOR, which was well accepted to positively regulate Th17 differentiation. Collectively, our results demonstrated that Ca 2+ -CaMK4-Akt/mTOR-IL-17A axis inhibition may serve as a promising therapeutic strategy for CP/CPPS., (© 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Depressive symptoms are found in approximately 78% of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) patients, but the pathological mechanisms remain unknown. Increasing evidence suggests that abnormal gut microbiota may play an important role in depression. Thus, we aimed to investigate whether gut microbiota contributes to CP/CPPS-associated depression by using a mouse model of experimental autoimmune prostatitis (EAP)., Methods: Male nonobese diabetic mice were immunized twice by subcutaneous injection of prostate antigen and adjuvant. Behavioral tests consisted of an open field test, sucrose preference test, forced swimming tests, and tail suspension test was used to confirm the depression-like symptoms that were induced by EAP. Then, fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition between control and EAP group. Additionally, fecal bacteria from the control and EAP mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on host behaviors and the composition of gut bacteria., Results: EAP was successfully established and exhibited depressive-like behaviors in mice. The 16S rRNA analysis of fecal samples indicated the abnormal composition of gut microbiota in the EAP mice compared to the control mice. In the fecal microbiota transplant study, antibiotics-treated pseudo-germ-free mice presented depressive states as compared to naïve mice. Fecal bacteria transplant from EAP mice, but not from control mice, into the pseudo-germ-free mice, significantly exaggerated host depression-like behaviors. Moreover, fecal bacteria transplants from control and EAP mice induced distinct alterations in α-diversity and β-diversity indices. In all, 24 bacteria at six phylogenetic levels were remarkably changed by the fecal bacteria transplantation., Conclusions: Abnormal gut microbiota composition after EAP induction may contribute to the development of depression in mice. A therapeutic strategy that targets gut microbiota may provide an alternative treatment for alleviating this condition., (© 2020 Wiley Periodicals, Inc.)

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent disease of the urogenital system. Alcohol has been reported to be closely related to CP/CPPS. Thus, we intended to verify the role of alcohol in CP/CPPS and determine the underlying mechanism., Methods: We induced experimental autoimmune prostatitis (EAP) mouse model by intradermally injecting a mixture of prostate antigens (PAgs) and complete Freund's adjuvant on days 0 and 28. Mice were treated with alcohol (control-alcohol and EAP-alcohol groups) or vehicle (control-vehicle, and EAP-vehicle groups) from day 32 to 42. Forty-two days after PAg injection, the pathological appearance of the prostate tissues was evaluated, and histological analyses of the prostate were performed. Chronic pelvic pain was assessed by applying von Frey filaments to the lower abdomen. Proinflammatory cytokines were detected by enzyme-linked immunosorbent assay tests. Then, we explored the effects of the NLRP3 inhibitor MCC950 on chronic pelvic pain and prostatic inflammation in this model., Results: Histological analyses showed diffuse inflammation in the stromal tissues that were characterized by severe infiltration of neutrophils and mononuclear cells in mice in the EAP-alcohol group compared with EAP-vehicle group. Chronic pain tests showed that the response frequency was significantly increased using a von Frey filament at forces of 0.4, 1.0, and 4.0 g in EAP-alcohol group compared with EAP-vehicle (P < .05). The levels of proinflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17, and IL-1β were all significantly elevated in EAP-alcohol group compared with the EAP-vehicle group (P < .05). However, between the control-alcohol and control-vehicle groups, chronic pain tests, histological assays, and cytokine determinations showed no differences. Furthermore, our results demonstrated that MCC950 could decrease the expression level of NLRP3 inflammasome-related proteins including NLRP3, ASC, and caspase-1. The chronic pain tests, histological assays, and cytokine determinations showed that MCC950 could attenuate the chronic pain and prostatic inflammation through the inhibition of the NLRP3 inflammasome., Conclusions: This study indicated that alcohol could aggravate the severity of prostatic inflammation in EAP model though activating the NLRP3 inflammasome. Furthermore, the role of MCC950 in inhibiting NLRP3 inflammasome and decreasing IL-1β secretion to alleviate EAP severity may show that it is a promising therapeutic agent for CP/CPPS., (© 2019 Wiley Periodicals, Inc.)

MicroRNAs (miRNAs) are considered to be involved in the pathogenic initiation and progression of chronic nonbacterial prostatitis (CNP); however, the comprehensive expression profile of dysregulated miRNAs, relevant signaling pathways, and core machineries in CNP have not been fully elucidated. In the current research, CNP rat models were established through the intraprostatic injection of carrageenan into the prostate. Then, next-generation sequencing was performed to explore the miRNA expression profile in CNP. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) bioinformatical analyses were conducted to reveal the enriched biological processes, molecular functions, and cellular components and signaling pathways. As a result, 1224, 1039, and 1029 known miRNAs were annotated in prostate tissues from the blank control (BC), normal saline injection (NS), and carrageenan injection (CAR) groups (n = 3 for each group), respectively. Among them, 84 miRNAs (CAR vs BC) and 70 miRNAs (CAR vs NS) with significantly different expression levels were identified. Compared with previously reported miRNAs with altered expression in various inflammatory diseases, the majority of deregulated miRNAs in CNP, such as miR-146b-5p, miR-155-5p, miR-150-5p, and miR-139-5p, showed similar expression patterns. Moreover, bioinformatics analyses have enriched mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), endocytosis, mammalian target of rapamycin (mTOR), and forkhead box O (FoxO) signaling pathways. These pathways were all involved in immune response, which indicates the critical regulatory role of the immune system in CNP initiation and progression. Our investigation has presented a global view of the differentially expressed miRNAs and potential regulatory networks containing their target genes, which may be helpful for identifying the novel mechanisms of miRNAs in immune regulation and effective target-specific theragnosis for CNP.

This study aims to validate our hypothesis that acid-sensing ion channels (ASICs) may contribute to the symptom of pain in patients with chronic prostatitis (CP). We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASIC1a was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASIC1a on the Ca 2+ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium ([Ca 2+ ]i) intensity. The effect of ASIC1a on the p38/mitogen-activated protein kinase (MAPK) signaling pathway was also determined. ASIC1a was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASIC1a expression increased [Ca 2+ ]i intensity in the dorsal horn neurons of rat spinal cord. ASIC1a also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASIC1a knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.

Chronic prostatitis is a common male disease with a high incidence rate and a serious impact on the patients' quality of life. The pathogenesis of chronic prostatitis remains unclear though it is considered to be possibly related to infection, inflammation, and abnormal pelvic nerve muscle activity. Recently, a growing number of studies have reported immune imbalance and changes of inflammatory cytokines in patients with chronic prostatitis as well as a close correlation of abnormal immune response with the occurrence of diseases, pelvic pain symptoms, mental symptoms, hyperalgesia, and so on. This review summarizes the latest advances in the studies of immunologic mechanisms of chronic prostatitis.

Although chronic nonbacterial prostatitis (CNBP) is a common diagnosis in middle-aged men, the etiology of this disease remains poorly understood. Neuroendocrine cells play an important role in the neuroendocrine regulation of the prostate, and chromogranin A (CgA) and neuron-specific enolase (NSE) are regarded as classic markers of neuroendocrine cells. This study aimed to determine CgA and NSE levels in a CNBP rat model to evaluate the role of neuroendocrine cells in the pathogenesis of CNBP. For developing a CNBP rat model, we examined the ability of 17-beta estradiol and surgical castration alone or in combination to induce CNBP. Histologic inflammation of the prostate was assessed in CNBP-induced rats by hematoxylin-eosin staining, whereas CgA and NSE protein levels were assessed by immunohistochemistry, Western blot analysis, and enzyme-linked immunosorbent assays. Our results showed that 17-beta estradiol combined with castration successfully induced CNBP and that CgA and NSE levels were increased in the prostate of CNBP rats as compared to those without CNBP. These findings indicate that the neuroendocrine regulation mediated by neuroendocrine cells may be involved in the pathogenesis of CNBP.

Objective: To investigate the impact of the BKCa channel in prostate smooth muscle cells (PSMCs) on the membrane potential in SD rats with chronic abacterial prostatitis (CAP)., Methods: CAP models were established in 20 SD rats by castration and injection of 17 beta-estrogen, and another 20 were taken as normal controls. PSMCs were cultured and purified in vitro, and treated with DiBAC4, followed by quantitative observations on the dynamic changes of the cell membrane potential by laser confocal microscopy., Results: The extracellular calcium ion concentration ([Ca2+]o) was increased and the BKCa channel was activated, which induced the hyperpolarization of the PSMC membrane in both the CAP models and normal control rats. This effect was weakened with Iberiotoxin (IbTX), a specific blocker of the BKCa channel, but the amplitude of the hyperpolarization was obviously lower in the CAP than in the control group. The DiBAC4 fluorescence intensity induced by hyperpolarization was 18.78 +/- 2.92 in the former and 38.85 +/- 7.10 in the latter (P < 0.05), while that induced by IbTX was 1.61 +/- 0.46 and 6.12 +/- 1.32 (P < 0.05), respectively., Conclusion: Significant decrease of BKCa-mediated hyperpolarization in the CAP model can reduce its abilities of regulating the membrane potential and suppressing the excessive contraction of PSMCs, which may result in pelvic pain syndrome and lower urinary tract symptoms.

Neuroendocrine cells are abundant in all the body tissues and organs as well as the nervous system, either the central or the peripheral nervous system. In the normal prostate tissue, there are a few neuroendocrine cells, too, in addition to basal and epithelial cells. Prostatic neuroendocrine cells play the function of regulating the development, secretion and differentiation of the prostate. Recent studies show that prostatic neuroendocrine cells may be involved in the pathogenesis of chronic prostatitis through their activity and secreted products. This article presents an overview on the origin, distribution, morphology, structure, secretion and functions of prostatic neuroendocrine cells and their association with chronic prostatitis.

This study was performed to evaluate the prevalence of erectile dysfunction (ED) and to explore its correlation to chronic prostatitis in China. A cross-sectional investigation from a large cohort study of Chinese men was used in this survey. A questionnaire consisting of general information regarding socio-demographics, chronic disease history, sexual function, the National Institutes of Health-Chronic Prostatitis Symptom Index, and the International Index of Erectile Function-5 (IIEF-5) was administered to 15 000 Chinese men aged from 15 to 60. The prevalence of ED was determined from the patient's self-evaluation and IIEF-5 score. The eligible individual both was married and had intercourse experience. In total, there were 12 743 respondents, giving a response rate of 84.95%. Among 7372 eligible men, ED prevalence as assessed by self-report and IIEF-5 score was 12.0% and 17.1%, respectively. Among 771 men with prostatitis-like symptoms, ED prevalence as assessed by self-report and IIEF-5 score was 39.3% and 30.1%, respectively. Among 370 men suffering from chronic prostatitis, ED prevalence as assessed by self-report and IIEF-5 score was 40.5% and 35.1%, respectively. The prevalence of self-reported and IIEF-5 score-assessed ED had high correlation with increasing age among all eligible men, men with prostatitis-like symptoms, and men with chronic prostatitis (P(t) < .05, P(s) < .05, P(cp) < .05). ED prevalence as assessed by both self-report and IIEF-5 score was higher in men with prostatitis-like symptoms and with chronic prostatitis than in the general group (P(s) < .05, P(cp) < .05). The prevalence of ED was higher in the prostatitis population than in the general population with either self-reported or IIEF-5 score assessment. The prevalence was higher with self-reported than with IIEF-5 assessment in men with prostatitis. Estimates of ED prevalence among men with prostatitis should not rely on self-reporting alone in that this is likely to overestimate the true prevalence.

Objective: To investigate the difference in intracellular calcium ion [Ca2+]i concentration in prostate smooth muscle cells (PSMCs) between SD rat models of chronic abacterial prostatitis (CAP) and normal controls, and to evaluate the role of [Ca2+]i concentration in CAP., Methods: We established CAP models in SD rats using purified prostate protein and Freund's complete adjuvant, cultured in vitro and then purified the PSMCs of both the CAP models and normal controls. Continuous dynamic scanning was performed under the laser confocal scanning microscope after incubation of the cells with FLUO-3AM., Results: The fluorescence intensities of [Ca2+]i in the PSMCs were 80.39 +/- 9.00 and 27.95 +/- 10.04 in the CAP models and normal controls, respectively, with statistically significant differences between the two groups (P < 0.01)., Conclusion: The concentration of [Ca2+]i increased in the PSMCs of the CAP rat models, which might enhance the constriction of PSMCs and subsequently increase the sensibility to pain and cause lower abdominal pain.

Objectives: Chronic pelvic pain syndrome is a common and serious health problem affecting the quality of life of men. We evaluated the prevalence of premature ejaculation (PE) in Chinese men with chronic pelvic pain syndrome and studied its correlation to chronic prostatitis., Methods: A total of 15,000 men (aged 15-60 years) were randomly recruited to take part in a survey to provide questionnaire-elicited information for sociodemographics, sexual function, National Institutes of Health-Chronic Prostatitis Symptom Index, and International Index of Erectile Function 5-item questionnaire. The eligible subjects of the present investigation were married with sexual activity., Results: Responses were collected from 12 743 men (84.95%). Of these men, 1071 (8.4%) reported having prostatitis-like symptoms. The incidence of chronic prostatitis was 4.5% (n = 571) for the entire group. Of the 7372 eligible men, the incidence of prostatitis-like symptoms, chronic prostatitis, and PE was 10.5% (n = 771), 5.0% (n = 370), and 15.3% (n = 1127), respectively. The group with PE had worse National Institutes of Health-Chronic Prostatitis Symptom Index scores (P < .05) and lower International Index of Erectile Function 5-item questionnaire scores (P < .05) than the patients without PE. Also, the percentage of prostatitis-like symptoms in the PE group was greater than that in the non-PE group (P < .05). The prevalence of PE was 64.1% and 36.9% in the prostatitis-like symptom and chronic prostatitis group, respectively, of the 7372 eligible men., Conclusions: The results of our study showed a high prevalence of PE in patients with chronic prostatitis. An examination of the prostate, physically and microbiologically, should be considered during the assessment of patients with PE., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To construct a rat model of chronic nonbacterial prostatitis (CP) and investigate the difference in the quantitative expression of voltage-dependent calcium channels of prostate smooth muscle cells (PSMCs) between the models and controls., Methods: We established a CP rat model by estrogen induction, cultured and purified the PSMCs in vitro, and extracted total RNA by Trizol. Then we measured the mRNA expression of the cal subunit in the calcium channel subtypes by reverse transcription and SYBR Green I real time RT-PCR, and compared it with that of the controls., Results: The expressions of the L-, T- and P/Q-type calcium channels were found in both the CP and control groups, and that of the CaV1.2 L-type calcium channel was significantly increased in the former as compared with the latter (0.048 +/- 0.024 versus 0.031 +/- 0.015, t = 2.846, P = 0.007), but there were no statistically significant differences in the T- and P/Q-type calcium channels between the two groups., Conclusion: The number of CaV1.2 L-type calcium channels of PSMCs and calcium influx were increased in CP patients, which may be involved in the mechanism of CP.

Purpose: We studied the prevalence of prostatitis-like symptoms and identified their associated risk factors in a population based Chinese sample., Materials and Methods: A volunteer group of 15,000 eligible men residing in Beijing, Anhui, Xi'an, Guangzhou and Gansu cities or provinces were invited randomly to take part in the survey to complete a questionnaire that elicited information regarding sociodemographics, Eysenck personality questionnaire, current stress and health ratings, lifestyle, medical history, expressed prostatic secretion evaluation, score of the National Institutes of Health Chronic Prostatitis Symptom Index and International Index of Erectile Function-5., Results: Information on 12,743 (84.95%) men was collected. Of these men 1,071 (8.4%) reported prostatitis-like symptoms (mean National Institutes of Health Chronic Prostatitis Symptom Index pain score 7.55 +/- 3.22). The percent of chronic prostatitis was 4.5% (571) among the symptoms group according to past urological history and expressed prostatic secretion evaluation. Subjects with prostatitis-like symptoms (mean age 34.56 +/- 13.48 years) had higher mean pain and urinary symptoms scores (7.53 +/- 3.22 and 2.84 +/- 2.72, respectively) compared with subjects without prostatitis-like symptoms (1.18 +/- 2.32 and 0.72 +/- 1.66 for pain and urinary symptoms scores, respectively, mean age 30.7 +/- 10.17) (pain and symptoms scores, p <0.05). The quality of life score was 6.03 +/- 2.88 and 3.83 +/- 2.55 in groups with symptoms or nonsymptoms, respectively (p <0.05)., Conclusions: Prostatitis-like symptoms are a multifactorial problem affecting men of all ages (15 to 60 years) and demographics, and the prevalence is high in China. The syndrome is closely related to alcohol consumption, cigarette smoking, frequent intercourse, as well as fatigue, pressure and too little sleep. These findings suggest that risk factors for this condition are largely modifiable and highlight potential targets for future prevention.

The aim of this study is to assess the status of treatment of chronic prostatitis (CP) in Chinese men. A population-based cross-sectional survey was performed, in which 15 000 men aged between 15 and 60 years were randomly selected to receive a questionnaire designed to assess National Institutes of Health Chronic Prostatitis Symptoms Index (NIH-CPSI) status, therapeutic efficacy and 28 other items. A total of 12 743 men (84.95%) completed the questionnaire, of whom 1 071 (8.4%) were identified as having prostatitis-like symptoms and 517 (4.5%) were diagnosed with CP according to NIH-CPSI criteria and prostatitis-like symptomatology. Of the CP patients, 372 (65%) underwent long-term routine treatment 12 times per year. Additionally, 217 (72.8%) patients received antibiotic therapy and 215 (79.3%) men showed therapeutic effects. The treatment cost USD 1 151 (8 059 yuan) per person per year on average. Most CP patients received routine treatment, in most cases with antibiotics. Treatment was costly and most CP patients were not satisfied with its effectiveness. Antibacterial treatment might have been effective primarily in patients with bacterial disease.

Chronic prostatitis (CP) is a common disease among adult men. It can result in male infertility mainly by alternating the semen quality, volume, pH, component, viscosity and liquefaction. There seems to be a strong association between CP and semen delayed liquefaction. Researches on the mechanism of semen delayed liquefaction resulting from CP mainly focus on the proteolytic ferment, plasminogen activator, prostate acid phosphatase, tissue factor, lack of zinc, and pH. This article briefly reviews the progress in these aspects.

Objective: To study the depression symptoms in chronic prostatitis (CP) patients, and explore the correlation between depression symptoms and CP., Methods: The Zung self-rating depression scale (SDS) , NIH-CPSI, IIEF-5, and a self-designed questionnaire were employed in 1500 cases of CP patients., Results: A total of 1426 effective questionnaires were collected. The mean score of SDS was (44.24 +/- 10.20), significantly higher than that of the domestic norm (P = 0.000). With the score limitation set at > or = 53, 309 (21.7%) of the CP patients had symptoms of depression, of whom 176 (12.3%) were rated by SDS as in the mild, 114 (8.0%) in the moderate and 19 (1.3%) in the severe state of depression. The dominating symptoms as listed in SDS were exactly the stimulating and provoking factors of CP. The scores of SDS were significantly correlated with disease course, CPSI score, IIEF score and times and cost of treatment (P < 0.01), while no correlation was observed with age and WBC counts in EPS., Conclusion: CP patients mostly have depression problems, which are closely correlated with CP and contribute to the recurrence, refractoriness and discontinued outcome of the disease.

Objective: To investigate the effect of the Kv1.3 K(+) channel on the pathogenesis of chronic prostatitis., Materials and Methods: The expression of the Kv1.3 K(+) channel in prostatic epithelia was detected using streptavidin/peroxidase immunohistochemistry in tissue samples from 75 men with benign prostatic hyperplasia, including 42 with and 33 without chronic inflammation. All of the men were sampled in our hospital between January 2000 and December 2003., Results: There was strong and moderate immunostaining in 14 of the prostatic epithelial specimens with inflammation and in 21 from patients without inflammation, compared to 28 and 12 with low staining, respectively (chi-squared, P < 0.05)., Conclusions: The expression of the Kv1.3 K(+)channel was lower in prostatic epithelial cells from patients with chronic inflammation than from those without. Opening the Kv1.3 K(+) channel could promote the efflux of K(+) from the cells, causing an increase in [K(+)] in the prostate cavity. The increase in [K(+)] can then infiltrate the stroma through the epithelial gap, exciting the nerve fibres and causing pain and other clinical symptoms.

This study was aimed at measuring concentration of electrolytes, especially K+ in expressed prostatic secretion (EPS) and urine from patients with chronic prostatitis. The concentration of potassium, sodium, chloride, calcium in EPS and urine of 31 controls and 79 patients with prostatitis were measured and analyzed. There was no significant difference in the concentrations of potassium, sodium, chloride and calcium between the patients and the controls. Among the patients treated effectively, potassium concentration was 40.66 +/- 17.10 mmol/l before treatment and 33.42 +/- 17.27 mmol/l after treatment. While among the patients treated ineffectively, potassium concentration was measured as 37.57 +/- 16.93 mmol/l and 50.66 +/- 18.77 mmol/l before and after treatment respectively. The concentrations of electrolytes in prostatic fluid varied greatly between individuals. Potassium concentration in EPS decreased significantly after treatment among the patients with obvious treatment effectiveness, while increased among those who failed the treatment. EPS potassium concentration was also found to be lower in patients with pain than those without pain. No significant difference was found between the normal group and the no-pain patients.

Chronic prostatitis (CP) is a common and painful disease in young and middle-aged men, with its causes remaining confused. In recent years, in-depth studies have been made on the interaction between CP and psychological hindrance. This review focuses on the manifestation and the mechanism of psychological hindrance in CP patients as well as on the effect of psychological therapy, and is meant to offer some reference to the etiology and semiology studies of CP.

Objective: To assess possible causes, clinical symptoms and improvements in treatment for chronic prostatitis in China., Patients and Methods: The study comprised 3000 patients with chronic prostatitis (aged 20-59 years), selected from urological clinics at province, city and county levels in Anhui (a province in mid-eastern China). Anonymous questionnaires were distributed which included 29 items to ascertain patient age, height, weight, educational background, personality, career, disease course, treatment status, prostatic fluid test and score of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI)., Results: In all, 2498 valid questionnaires were collected (response rate 83.3%); 78.2% of the patients were aged <40 years and there were fewer patients in groups of increasing age. Discomfort and pain in the pelvis was reported by 52.3%, pain on urination by 23.0%, sexual discomfort by 21.8%, urinary frequency by 65.8%, and voiding discomfort by 74.4%; 34.9% of men were satisfied with their previous treatment., Conclusion: In China there are fewer patients with chronic prostatitis as age increases. The main symptoms were voiding dysfunction, e.g. frequent urination. The prevalence of pain, e.g. on urination, was significantly less than documented in other parts of the world. Most patients had used antibiotics to treat their prostatitis; generally the effect of treating prostatitis was unsatisfactory.

Objective: To investigate the prevalence and risk factors of sexual dysfunction in Chinese men with chronic prostatitis., Patients and Methods: A questionnaire survey was conducted among 2000 men diagnosed as having chronic prostatitis using the National Institutes of Health Chronic Prostatitis Index and analysis of expressed prostatic secretions. The survey was designed to elicit information about age, height, weight, occupation and history of disease and treatment. The erectile capacity of the men was assessed using the five-question version of the International Index of Erectile Function., Results: Of the 2000 men with chronic prostatitis selected, 1786 completed the survey; the overall prevalence of sexual dysfunction in these patients was 49%. The prevalence of premature ejaculation and erectile dysfunction accounted for 26% and 15%, respectively; 7.7% had both premature ejaculation and erectile dysfunction. There was a negative correlation between prevalence and age, and with the duration of chronic prostatitis (both P < 0.001)., Conclusions: The prevalence rate of sexual dysfunction in Chinese men with chronic prostatitis is high and related to age.

To assess possible causes, clinical symptoms and improvements in treatment for chronic prostatitis in China. The study comprised 3000 patients with chronic prostatitis (aged 20–59 years), selected from urological clinics at province, city and county levels in Anhui (a province in mid-eastern China). Anonymous questionnaires were distributed which included 29 items to ascertain patient age, height, weight, educational background, personality, career, disease course, treatment status, prostatic fluid test and score of the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI). In all, 2498 valid questionnaires were collected (response rate 83.3%); 78.2% of the patients were aged <40 years and there were fewer patients in groups of increasing age. Discomfort and pain in the pelvis was reported by 52.3%, pain on urination by 23.0%, sexual discomfort by 21.8%, urinary frequency by 65.8%, and voiding discomfort by 74.4%; 34.9% of men were satisfied with their previous treatment. In China there are fewer patients with chronic prostatitis as age increases. The main symptoms were voiding dysfunction, e.g. frequent urination. The prevalence of pain, e.g. on urination, was significantly less than documented in other parts of the world. Most patients had used antibiotics to treat their prostatitis; generally the effect of treating prostatitis was unsatisfactory. [ABSTRACT FROM AUTHOR]

To investigate the prevalence and risk factors of sexual dysfunction in Chinese men with chronic prostatitis. A questionnaire survey was conducted among 2000 men diagnosed as having chronic prostatitis using the National Institutes of Health Chronic Prostatitis Index and analysis of expressed prostatic secretions. The survey was designed to elicit information about age, height, weight, occupation and history of disease and treatment. The erectile capacity of the men was assessed using the five-question version of the International Index of Erectile Function. Of the 2000 men with chronic prostatitis selected, 1786 completed the survey; the overall prevalence of sexual dysfunction in these patients was 49%. The prevalence of premature ejaculation and erectile dysfunction accounted for 26% and 15%, respectively; 7.7% had both premature ejaculation and erectile dysfunction. There was a negative correlation between prevalence and age, and with the duration of chronic prostatitis (both P < 0.001). The prevalence rate of sexual dysfunction in Chinese men with chronic prostatitis is high and related to age. [ABSTRACT FROM AUTHOR]