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Chronic prostatitis is a prevalent urological condition that significantly impacts patients’ quality of life. Advances in the study of Extracellular Vesicles (EV) have revealed their close involvement in the pathogenesis of prostatitis. This paper reviews the progress in understanding the role of EV in the pathogenesis of chronic prostatitis type IIIA, particularly their involvement in inflammatory responses, cell signaling, and interactions with immune cells. Additionally, it explores the potential applications of EV as drug delivery vehicles, including the targeted delivery of anti-inflammatory agents and immunomodulators, and highlights the challenges associated with developing exosome-based therapeutic strategies. In-depth research on EV holds promise for offering new insights into the diagnosis and treatment of inflammatory diseases.

Inflammation is inherent in prostatic diseases and it is now accepted that it may facilitate cellular proliferation in both benign and malignant conditions. The strong relationship between prostatic inflammation and pathogenesis of benign prostatic hyperplasia (BPH) is supported by epidemiologic, histopathologic and molecular evidence. Contrariwise, the role of inflammation in prostate carcinogenesis is still controversial, although current data indicate that the inflammatory microenvironment can regulate prostate cancer (PCa) growth and progression. Knowledge of the complex molecular landscape associated with chronic inflammation in the context of PCa may lead to the introduction and optimization of novel targeted therapies. In this perspective, evaluation of the inflammatory component in prostate specimens could be included in routine pathology reports.

Objectives:To report the one-year results of ESWT on CPPS patients and the possible clinical characteristics that may affect its efficacy.Patients & methods:A prospective randomized clinical study between January 2017 and January 2021 on 155 adult patients with chronic pelvic pain syndrome. All patients were initially evaluated with a thorough history and physical examination. Baseline symptoms evaluation of each participant was assessed using NIH-CPSI score, IPSS, VAS, and IIEF-5 score. Patients were randomized into two groups: a verum treatment group and a placebo treatment group. Patients of verum group in the lithotomy position received a perineally applied ESWT treatment once a week for four weeks with 3000 impulses each. Patients of placebo group received the same therapy head of the same device with a layer of air-filled microspheres to absorb the shock waves. The previously mentioned validated scores were reassessed on regular follow-up visits at one, three, six, and 12 months after the completion of ESWT.Results:A statistically significant improvement was noticed in the mean values of NIH-CPSI, IPSS, VAS, and IIEF-5 of the patients of verum group over the follow-up period with also statistically significant difference between both groups. At the first visit of follow-up after ESWT, 63 (82.8%) patients had ≥6 points decrease in the NIH-CPSI total score, while 13 (17.2%) patients did not. Univariate and multivariate analyses of the clinical characteristics between the responders and non-responders showed that those patients with history of psychological disorders or had higher initial NIH-CPSI score had a significantly lower response rate to ESWT (p = 0.005, 0.02 & p = 0.002, 0.004 respectively). ROC curve of NIH-CPSI score showed that a score of 32 was the cut-off point above which the response to ESWT decreased.Conclusion:ESWT is an effective treatment option for CPPS. Its efficacy remained throughout long-term follow up. High initial NIH-CPSI score and history of psychological problems are significant predictors for it.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that affects youthful to middle-aged men most frequently. It has been revealed that Th17/Treg imbalance is a crucial factor in the pathophysiological mechanisms behind this disease. However, this imbalance’s mechanisms are unknown. In the experimental autoimmune prostatitis (EAP) mouse model, the NLRP3 inflammasome was turned on, IL-1β levels went up. Moreover, there exists a discernible positive association between the upsurge in IL-1β and the perturbation of Th17/Treg equilibrium. Additionally, we have revealed that IL-1β plays a vital role in promoting the differentiation of Naïve CD4+ T cells into the Th17 cells and enhances the conversion of Treg cells into Th17 cells. Further studies revealed that IL-1β promotes STAT3 phosphorylation, which is what causes Treg cells to become Th17 cells. All data strongly suggest that the NLRP3 inflammatory influence Th17 cell development and the conversion of Treg cells into Th17 cells through IL-1β, disrupting the Th17/Treg balance and exacerbating EAP inflammation. In this article, we provide new theories for the pathogenesis of CP/CPPS and propose new prevention and therapy methods.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder associated with voiding symptoms and pain in the pelvic or perineal area. Macrophages, particularly the pro-inflammatory M1 subtype, are crucial initiating of CP/CPPS. Interferon regulatory factor 7 (Irf7) has been implicated in promoting M1 polarization, contributing to the onset and progression of autoimmunity. However, the role of Irf7 in the etiology and progression of CP/CPPS remains unclear. Method We established the experimental autoimmune prostatitis (EAP) mouse model by subcutaneous injection of prostate antigen combined with complete Freund’s adjuvant. Six weeks after the first immunization, we analyzed the prostates, spleen, and blood to assess the degree of prostate inflammation, Irf7 expression levels, glycolysis, and M1 polarization to evaluate whether Irf7 could exacerbate the development of EAP by enhancing Hif-1α transcription, thereby increasing glycolysis and M1 polarization. Further investigations included sh-Irf7 intervention, Dimethyloxalylglycine (a Hif-1α agonist), and in vitro M1 polarization experiments. We also employed ChIP assays, dual-luciferase reporter assays, and q-PCR to explore if Irf7 could directly interact with the Hif-1α promoter in macrophages. Results In the EAP mouse and cell models, elevated Irf7 expression was observed in inflamed tissues and cells. Reducing Irf7 expression decreased M1 cell glycolysis by inhibiting the nuclear translocation of Hif-1α, thus mitigating M1 cell polarization. Additionally, Irf7 was identified as a transcription factor that regulates Hif-1α transcription by interacting with its promoter in macrophages, confirmed through ChIP and dual-luciferase assays. Co-culturing macrophage cells with 3T3 fibroblasts with reduced Irf7 levels resulted in decreased fibrosis, and a significant reduction in prostate tissue fibrosis was noted in mice with Irf7 knockdown. Conclusion Our findings indicate that Irf7 can contribute to the development and progression of CP/CPPS by promoting glycolysis, which can enhance both M1 polarization as well as interstitial fibrosis in the prostate. This process was found to be mediated by the upregulation of Hif-1α transcription, presenting new potential therapeutic targets for managing CP/CPPS.

•We compared immune functions in patients treated with acupuncture or sham.•Levels of natural killer cells were significantly higher in acupuncture patients.•Changes in other leukocyte parameters were also higher in the acupuncture group.•These findings provide ‘proof-of-concept’ supporting future studies for acupuncture. The immune system has been implicated as one mechanism underlying the benefits of acupuncture therapy. Evidence suggests that acupuncture can ameliorate symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but the association between clinical response and the immune system has not been investigated. We investigated 12 CP/CPPS patients participating in a prospective randomized clinical trial comparing acupuncture versus sham acupuncture for effects on cellular immunity. Blood samples were taken before the first needling and after the last of 20 treatment sessions (week 10). Patients also completed questionnaires examining their CP/CPPS symptoms and mood status at the baseline and end of study visits. At the end of study 8 of 12 participants (67%) were classified as treatment responders, four participants each from the acupuncture and sham groups. The acupuncture group averaged a 5% increase in natural killer cell levels compared to corresponding sham (−13%; p=0.03). Similarly, patients randomized to acupuncture reported a reduction in other white blood cell parameters examined, supporting the possibility that immunity might be important in the pathophysiology of CP/CPPS. The specific effect of acupuncture on CP/CPPS remains unclear. Further research is warranted to examine the mechanisms by which acupuncture therapy may improve clinical symptoms in patients with CP/CPPS. Trial registration: ClinicalTrials.gov number, NCT00260637)

PurposeTo evaluate the efficacy and safety of Escherichia coli Nissle 1917 (EcN) in association with levofloxacin in patients with chronic bacterial prostatitis (CBP).MethodsPatients with CBP referred to our clinic from September 2017 to July 2019 were enrolled. At baseline, the symptomatology was assessed with the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), while the Meares–Stamey test was used to diagnose the infection. Patients were randomized (1:1) in two groups (A and B). All subjects underwent oral administration of Levoxacin® 500 mg once daily for 4 weeks. Only the patients in Group B underwent oral administration of EcN® 320 mg, twice daily for 4 weeks and then once daily for 8 weeks. After 3 months, each patient repeated the NIH-CPSI questionnaire, while the Meares–Stamey test was repeated at 3 and 6 months in patients who reported persistent symptoms. All adverse events (AEs) were recorded.ResultsA total of 110 patients were enrolled. After 3 months patients in Group B reported a significantly lower NIH-CPSI score (5.85 ± 3.07 vs. 7.64 ± 3.86; p = 0.009) and biological recurrences rate (9.8 vs. 26.9%; p = 0.043). At 6 months the biological recurrences rate was significantly lower in Group B (8.7 vs. 28.9%; p = 0.038). Only three patients in Group A and six in Group B (p = 0.25) complained mild AEs.ConclusionsCombination therapy with EcN and levofloxacin allows a better control of symptoms and biological recurrences in patients with CBP, without worsening the safety of the treatment.

Cumulative evidence suggests that abnormal differentiation of T lymphocytes influences the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Thus, understanding the immune activation landscape of CP/CPPS would be helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10 000+ AbSeq profiles and identified fifteen unique T‐cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) was significantly increased compared with the proportion in the healthy control group (9.38%); cluster 0 was defined as effector T cells based on differentially expressed genes/proteins. Flow cytometry assays confirmed that the proportions of effector T‐cell subpopulations, particularly central memory T cells, T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell populations of patients with CP/CPPS were significantly increased compared with those of healthy controls (P < 0.05), further confirming that aberration of effector T cells possibly leads to or intensifies CP/CPPS. Our results provide novel insights into the underlying mechanisms of CP/CPPS, which will be beneficial for its treatment.

Background C-X-C receptor 4(CXCR4) is widely considered to be a highly conserved G protein-coupled receptor, widely involved in the pathophysiological processes in the human body, including fibrosis. However, its role in regulating macrophage-related inflammation in the fibrotic process of prostatitis has not been confirmed. Here, we aim to describe the role of CXCR4 in modulating macrophage M1 polarization through glycolysis in the development of prostatitis fibrosis. Methods Use inducible experimental chronic prostatitis as a model of prostatic fibrosis. Reduce CXCR4 expression in immortalized bone marrow-derived macrophages using lentivirus. In the fibrotic mouse model, use adenovirus carrying CXCR4 agonists to detect the silencing of CXCR4 and assess the in vivo effects. Results In this study, we demonstrated that reducing CXCR4 expression during LPS treatment of macrophages can alleviate M1 polarization. Silencing CXCR4 can inhibit glycolytic metabolism, enhance mitochondrial function, and promote macrophage transition from M1 to M2. Additionally, in vivo functional experiments using AAV carrying CXCR4 showed that blocking CXCR4 in experimental autoimmune prostatitis (EAP) can alleviate inflammation and experimental prostate fibrosis development. Mechanistically, CXCR4, a chemokine receptor, when silenced, weakens the PI3K/AKT/mTOR pathway as its downstream signal, reducing c-MYC expression. PFKFB3, a key enzyme involved in glucose metabolism, is a target gene of c-MYC, thus impacting macrophage polarization and glycolytic metabolism processes.

Prostate adenocarcinoma is the second most commonly diagnosed cancer in men worldwide, and the initiating factors are unknown. Oncogenic TMPRSS2:ERG (ERG+) gene fusions are facilitated by DNA breaks and occur in up to 50% of prostate cancers. Infection-driven inflammation is implicated in the formation of ERG+ fusions, and we hypothesized that these fusions initiate in early inflammation-associated prostate cancer precursor lesions, such as proliferative inflammatory atrophy (PIA), prior to cancer development. We investigated whether bacterial prostatitis is associated with ERG+ precancerous lesions in unique cases with active bacterial infections at the time of radical prostatectomy. We identified a high frequency of ERG+ non–neoplastic-appearing glands in these cases, including ERG+ PIA transitioning to early invasive cancer. These lesions were positive for ERG protein by immunohistochemistry and ERG messenger RNA by in situ hybridization. We additionally verified TMPRSS2:ERG genomic rearrangements in precursor lesions using tricolor fluorescence in situ hybridization. Identification of rearrangement patterns combined with whole-prostate mapping in three dimensions confirmed multiple (up to eight) distinct ERG+ precancerous lesions in infected cases. We further identified the pathogen-derived genotoxin colibactin as a potential source of DNA breaks in clinical cases as well as cultured prostate cells. Overall, we provide evidence that bacterial infections can initiate driver gene alterations in prostate cancer. In addition, our observations indicate that infection-induced ERG+ fusions are an early alteration in the carcinogenic process and that PIA may serve as a direct precursor to prostate cancer.