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.

Should we review our prophylaxis approach for increased antibiotic resistance in transrectal prostate biopsy?

INTRODUCTION: This study aims to show the bacteriologic picture of acute prostatitis and bacteremia caused by infective agent after transrectal ultrasound-guided prostate biopsy (TRUSBx) and to determine the resistance rates of the infections in patients undergoing transrectal biopsy and to guide prophylaxis approach before biopsy. METHODOLOGY: The retrospective data of 935 patients who underwent TRUSBx between January 2010 to January 2019 were reviewed. Pre-biopsy urine cultures and antimicrobial susceptibility were obtained. Subsequently, patients admitted to the hospital with any complaint after biopsy were examined for severe infection complications. RESULTS: Of the 430 (61.7%) patients who underwent urine culture before the procedure, 45 (10.5%) had growth; 30 (66.7%) of the growing microorganisms were Escherichia coli. Twenty (44.4%) of all Gram-negative agents in pre-biopsy urine culture were susceptible to quinolone. Post TRUSBx bacteremia was present in 18.2%, urinary system infection in 83.6%, and hospitalization in 61.8% of 55 patients who were admitted to the hospital. In the isolated gram-negative microorganisms, fluoroquinolones resistance in urinary system infections was seen in 40% and bacteremia was seen in 70% of the cases. ESBL-producing Gram-negative bacteria were determined in 40% of infections in blood and 38.5% of urinary system infections in the post biopsy period in the current study. CONCLUSIONS: These high antibiotic resistance rates suggest that we better review our pre-procedure prophylaxis approaches.

The microbiota of sexual intercourse and its effect on prostatitis.

It is estimated that microorganisms colonize 90% of the body surface. In some tracts, such as the genitourinary tract, the microbiota varies throughout life, influenced by hormonal stimulation and sexual practices. This study evaluated the semen differences and presence of Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis and Atopobium vaginae in semen samples from patients with symptoms of chronic prostatitis and men asymptomatic for urogenital infections. Fifty-three semen samples were included: 22 samples from men with symptoms of chronic prostatitis and 31 asymptomatic men (control group). In addition to the presence of L. crispatus, L. iners, G. vaginalis and A. vaginae, semen parameters, total antioxidant capacity of seminal plasma, prostatic antigen and some proinflammatory cytokines were evaluated in each semen sample. Volunteers with symptoms of chronic prostatitis presented a lower percentage of sperm morphology (4.3% vs. control group 6.0%, p = 0.004); in the semen samples of volunteers in the group asymptomatic for urogenital infections, microorganisms associated with the vaginal microbiota were detected more frequently. The presence of bacteria in the vaginal microbiota can also benefit male reproductive health, which undergoes various modifications related to lifestyle habits that are susceptible to modification. Microorganisms associated with the vaginal microbiota, such as L. crispatus, L. iners, G. vaginalis and A. vaginae, may have a protective role against the development of male genitourinary diseases such as prostatitis.

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.

[Practical use of Adenoprosin in combination therapy in men with lower urinary tract symptoms].

AIM: The aim of the observational cohort study is to study and evaluate the efficiency of the drug Adenoprosin in combination with other drugs in comparison with monotherapy. MATERIALS AND METHODS: Data from 6,442 patients at 221 medical institutions in 39 cities from November 2020 to December 2022 were analyzed. The drug Adenoprosin in the form of rectal suppositories was prescribed as monotherapy in group I, while patients in group II received Adenoprosin in a combination with other drugs. The efficacy of treatment was assessed using uroflowmetry data, prostate volume, postvoid residual volume and validated scales (NIH-CPSI, IIEF-5, IPSS, QoL). RESULTS: The diagnosis was validated in 6375 cases, including BPH (n=1498), chronic prostatitis (CP; n=3060), and in combination of both disorders (n=1817). A total of 3580 patients received Adenoprosin as monotherapy, while 2761 received combination therapy. In most cases, a combination therapy was prescribed in case of more severe disease. In patients with BPH, positive changes after treatment were noted in favor of group I according to change in postvoid residual volume (p<0.001) and prostate volume (p<0.001). Combination therapy demonstrated significant positive changes compared with monotherapy when assessing NIH-CPSI scores (p=0.005), IPSS scores (p<0.001) and the mean maximum urine flow rate (Qmax; p<0.001). Qmax increased significantly in both groups (from 14 ml/s to 17 ml/s in group I and from 12 ml/s to 14 ml/s in group II). CONCLUSION: Treatment of BPH, CP and their combination is a complex clinical task. The multiple nature of complaints often dictates the need for simultaneous administration of two or more drugs. Combination therapy involves the use of multiple therapeutic strategies to treat different aspects of BPH and CP. In patients with BPH, a combination therapy has been shown to be more effective than monotherapy with either class of drugs, as it reduces the risk of disease progression, acute urinary retention, and the need for surgery. However, combination therapy should be considered on an individual basis, taking into account symptoms, prostate size and overall health. There is no universal treatment method for BPH suitable for any patient. The treatment strategy should be chosen individually, considering all medical and social factors. All of the above applies to a large extent to the treatment of CP and CP + BPH. According to our results, Adenoprosin demonstrated efficacy both as monotherapy and in combination with other traditional drugs in the treatment of men with lower urinary tract symptoms.

[Metabolic features of the inflammatory syndrome of chronic pelvic pain (category IIIA of chronic non-bacterial prostatitis) in young men, depending on the somatotype].

PURPOSE: dentification of bioimpedance and clinical features in young men with chronic pelvic pain inflammatory syndrome (CP/CPPS NIH IIIa) depending on the somatotype. METHOD: s. 150 men of the first period of adulthood from 22 to 35 years old with CP/CPPS NIH IIIa were examined from 2018 to 2022 years. The average age was 31 [28; 34] year. Somatotypes were computed according to Carter and Heath. Body composition was assessed anthropometry and bioimpedance analysis. RESULTS: Ectomorphs had the least clinical, laboratory and instrumental manifestations of CP/CPPS NIH IIIa, the levels of total and free testosterone were the highest. The active cell mass predominated in the component composition of the body. Manifestations in mesomorphs had a moderate degree of severity. Endomorphs had the most severe manifestations of CP/CPPS NIH IIIa, the largest amount of fat mass was noted in the body composition than in men of other somatotypes, the hormonal status was characterized by the lowest levels of free and total testosterone, and the highest level of estradiol. DISCUSSION: Based on the literature data and our own results, it can be assumed that the identified changes in the body component composition and hormonal status of men contribute to the maintenance of chronic inflammation in the prostate, organ ischemia, impaired intracranial metabolism, recurrent course of CP/CPPS NIH IIIa, which significantly reduces the patients quality of life and increases the risk of prostate inflammation with age. CONCLUSION: Determining the somatotype and conducting a component analysis of body composition allows patients to be divided into groups according to the severity of manifestations of CP/CPPS NIH IIIa. The revealed patterns allow us to classify male endomorphs into the group with the most severe manifestations of CP/CPPS NIH IIIa.

[Evaluation of the effectiveness of various regimens of the immunomodulatory drug Superlimf in the prevention of relapses of chronic abacterial prostatitis].

INTRODUCTION: Immune defense mechanisms, including a decrease in the functional activity of monocytes/macrophages, neutrophils, as well as a violation of the balance of pro- and anti-inflammatory cytokines, are important in the development of chronic abacterial prostatitis (CAP). The discovery of the cytokine system and the determination of their biological role in the development and functioning of the immune system and in the pathogenesis of a wide range of human diseases led to the development of a new direction in immunotherapy - cytokine therapy. The aim of the study was to evaluate the effectiveness of various regimens of the use of the immunomodulatory drug Superlimf in the prevention of recurrence of CAP. MATERIALS AND METHODS: The study included 90 patients with category IIIa CAP (NIH, 1995). All patients underwent basic complex therapy was performed, which included behavioral therapy, taking an 1-adrenoblocker, an antibacterial drug from the fluoroquinolone group for 28 days, as well as the drug Superlimph 10 ME 1 suppository rectally 2 times a day for 20 days. Dynamic follow-up was recommended for patients of group (CG) in the next 12 months. In the main group 1 (MG1), patients underwent basic complex therapy, after which a preventive courses of Superlimph 10 ME 1 suppository 1 time per day for 10 days every three months for 12 months was prescribed. In the main group 2 (MG2), patients also underwent basic complex therapy, after which a preventive courses of Superlimph 10 ME of 1 suppository was prescribed 2 times a day for 10 days every three months for 12 months. The effectiveness of the treatment was evaluated after 4 weeks (visit 2). Long-term treatment results were assessed after 3 months (visit 3), 6 months (visit 4), and 12 months (visit 5). RESULTS: The study groups were homogeneous, and the results of examinations obtained before treatment did not differ statistically significantly (p>0.05). At visit 2, 4 weeks after the start of therapy, a statistically significant positive dynamics of the studied indicators in the main groups and CG was recorded. Thus, the average score on the IPSS scale decreased by 56.4% from the initial value, on the Qol scale - by 57.7%, on the NIH-CPSI scale - 70.2%. The number of leukocytes in the prostate secretion decreased to the normal level to 7.9 in the field of vision, which is 86.2% less than the initial value. The average Qmax value also increased to a normal value of 15.2ml/s, which is 51.3% higher than the initial value (p<0.001). In this study, for the first time, a comparative analysis of two different regimens of preventive administration of the drug Superlimf was carried out. In MG1, the drug was prescribed to patients at a dose of 10 ME 1 time a day, in MG2 - 10 ME 2 times a day. The data obtained indicate a comparable effectiveness of both dosage regimens after 3 months of therapy. However, after 6 months and 12 months, the results in MG2 were statistically significantly better than in MG1. In addition, during 12 months of therapy, the number of relapses in MG2 was 2.3 times less. According to ultrasound examination, the volume of the prostate gland in CG, after a significant (p<0.001) decrease against the background of basic complex therapy, increased by 24.6% from visit 2 to visit 5, whereas in MG2 the average value of this indicator did not significantly change. And according to the Doppler study, by the end of the observation period at visit 5, hemodynamic parameters in CG were statistically significantly worse than in MG1 and MG2. CONCLUSION: Thus, the use of Superlymph in patients with CAP as a preventive therapy every 3 months results to a longer preservation of the therapeutic effect and improved hemodynamics in the prostate. In addition, preventive courses of Superlymph 10 units 2 times a day for 10 days led to an increase in the duration of the relapse-free period and a decrease in the number of recurrences within 12 months by 7 times, while preventive courses of Superlymph 10 units 1 time per day for 10 days decreased risk of recurrence by 3 times. According to our results, the most effective preventive scheme in patients with CAP is the use of Superlymph 10 units, 1 suppository 2 times a day for 10 days every 3 months.

[The use of antioxidants in combination therapy of chronic prostatitis].

Currently, the significance of the chronic prostatitis (CP) is undoubted. Oxidative stress is considered as one of the standard mechanisms of cellular damage that is associated with inflammatory diseases such as CP. When choosing the combination therapy for this group of patients, a correction of oxidative stress is pathogenetically justified. Literature data about the pathogenetic feasibility and prospects of using a biologically active complex containing flavonoids and carotenoids quercetin, lycopene and naringin as part of the combination treatment of patients with CP are presented in the article. Considering the various effects of the biologically active complex Querceprost, containing quercetin, lycopene and naringin, among which antioxidant, anti-inflammatory, antimicrobial and immunomodulatory are of greatest importance, as well as taking into account the synergistic effect of flavonoids and carotenoids, we suggest that Querceprost is promising component of combination treatment of patients with CP.

Psychological and sexological assessment of patients with chronic prostatitis.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a multiform clinical presentation requiring a differentiated treatment based on different phenotypes including the psychosocial and sexual domains. The aim of this study was assessing the complex correlations between somatic, psychological, and sexual symptoms of CP/CPPS patients. MATERIALS AND METHODS: We performed a cross-sectional study on patients attending a Prostatitis Clinic. Patients were administered the following questionnaires: National Institutes of Health- Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF), Premature Ejaculation Diagnostic Tool (PEDT), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Oxford Happiness Questionnaire (OHQ), and Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). RESULTS: Linear regression analyses show highly significant correlations between scores of the NIH-CPSI and the scores of the GAD-7, PHQ-9 and OHQ psychometric questionnaires. IPSS scores correlate significantly with the psychometric scores only when a non-parametric analysis is performed. IIEF and PEDT sexual function scores did not correlate with any of the psychometric tests. NIH-CPSI scores correlate positively with most of the TEMPS-A profiles but the hyperthymic profile correlated negatively with the total and QoL NIH-CPSI and with PEDT scores. CONCLUSIONS: Scores measuring anxiety, depression, and psychological well-being in patients with CP/CPPS are strictly correlated with prostatitis-like symptoms although they are poorly correlated with symptoms of prostatism, as measured by IPSS, and not correlated with scores of sexual dysfunctions, as measured by IIEF and PEDT. A hyperthymic temperament may increase resilience against the disease.

Trends in hospitalisation for urinary tract infection in adults aged 18-65 by sex in Spain: 2000 to 2015.

OBJECTIVE: To analyse trends in urinary tract infection (UTIs) hospitalisation among patients adults 18-65 aged in Spain from 2000-2015. METHODS: Retrospective observational study using the Spanish Hospitalisation Minimum Data Set (CMBD), with codifications by the International Classification of Diseases (ICD-9). Variables: Type of UTIs (pyelonephritis, prostatitis, cystitis and non-specific-UTIs), sex, age (in 5 categories: 18-49 and 50-64 years in men, and 18-44, 45-55 and 56-64 years in women), comorbidity, length of stay, costs and mortality associated with admission. The incidence of hospitalisation was studied according to sex, age group and type of UTIs per 100,000. Trends were identified using Joinpoint regression. RESULTS: From 2000-2015, we found 259,804 hospitalisations for UTIs (51.6% pyelonephritis, 7.5% prostatitis, 0.6% cystitis and 40.3% non-specific UTIs). Pyelonephritis predominated in women and non-specific UTIs in men. The hospital stay and the average cost (2,160 EUR (IQR 1,7872,540 were greater in men. Overall mortality (0.4%) was greater in non-specific UTIs. More women were admitted (rates of 79.4 to 81.7) than in men (30.2 to 41). The greatest increase was found in men aged 50-64 years (from 59.3 to 87). In the Joinpoint analysis, the incidence of pyelonephritis increased in women [AAPC 2.5(CI 95% 1.6;3.4)], and non-specific UTIs decreased [AAPC -2.2(CI 95% -3.3;-1.2)]. Pyelonephritis decreased in men [AAPC -0.5 (CI 95% -1.5;0.5)] and non-specific UTIs increased [AAPC 2.3 (CI 95% 1.9;2.6)] and prostatitis increased [AAPC 2.6 (CI 95% 1.4;3.7)]. CONCLUSIONS: The urinary infection-related hospitalisation rate in adults in Spain increased during the period 2000-2015. Pyelonephritis predominated in women and non-specific UTIs in men. The highest hospitalisation rates occurred in the women but the greatest increase was found in men aged 65-74. The lenght of stay and cost were higher in men.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

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

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

Elucidation of active components and target mechanism in Jinqiancao granules for the treatment of prostatitis and benign prostatic hyperplasia.

ETHNOPHARMACOLOGICAL RELEVANCE: Prostatitis and benign prostatic hyperplasia (BPH) are inflammations of the prostate gland, which surrounds the urethra in males. Jinqiancao granules are a traditional Chinese medicine used to treat kidney stones and this medicine consists of four herbs: Desmodium styracifolium (Osbeck) Merr., Pyrrosia calvata (Baker) Ching, Plantago asiatica L. and stigma of Zea mays L. AIM OF THE STUDY: We hypothesized that Jinqiancao granules could be a potential therapy for prostatitis and BPH, and this work aimed to elucidate active compounds in Jinqiancao granules and their target mechanisms for the potential treatment of the two diseases. MATERIALS AND METHODS: Jinqiancao granules were commercially available and purchased. Database-driven data mining and networking were utilized to establish a general correlation between Jinqiancao granules and the two diseases above. Ultra-performance liquid chromatography-mass spectrometry was used for compound separation and characterization. The characterized compounds were evaluated on four G-protein coupled receptors (GPCRs: GPR35, muscarinic acetylcholine receptor M3, alpha-1A adrenergic receptor α1A and cannabinoid receptor CB2). A dynamic mass redistribution technique was applied to evaluate compounds on four GPCRs. Nitric acid (NO) inhibition was tested on the macrophage cell line RAW264.7. Molecular docking was conducted on GPR35-active compounds and GPR35 crystal structure. Statistical analysis using GEO datasets was conducted. RESULTS: Seventy compounds were isolated and twelve showed GPCR activity. Three compounds showed potent GPR35 agonistic activity (EC50 < 10 µM) and the GPR35 agonism action of PAL-21 (Scutellarein) was reported for the first time. Docking results revealed that the GPR35-targeting compounds interacted at the key residues for the agonist-initiated activation of GPR35. Five compounds showed weak antagonistic activity on M3, which was confirmed to be a disease target by statistical analysis. Seventeen compounds showed NO inhibitory activity. Several compounds showed multi-target properties. An experiment-based network reflected a pharmacological relationship between Jinqiancao granules and the two diseases. CONCLUSIONS: This study identified active compounds in Jinqiancao granules that have synergistic mechanisms, contributing to anti-inflammatory effects. The findings provide scientific evidence for the potential use of Jinqiancao granules as a treatment for prostatitis and BPH.

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.

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.

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

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

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

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

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.

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

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