Regulatory role of BNP in the spinal center of rats with nonbacterial prostatitis.

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.

Impaired Semen Quality in Patients with Chronic Prostatitis.

Background/Objectives: Chronic prostatitis/chronic pelvic pain syndrome CP/CPPS is a rather common condition and in recent years many studies have shown contradictory results regarding its impact on semen quality. This prospective cohort study set out to investigate how CP/CPPS affected the parameters of semen in a prospective cohort of patients compared with the WHO 2021 reference group. Methods: From 2013 to 2022, a total of 1071 patients with suspicion of CP/CPPS received a comprehensive andrological examination. Complete semen analysis was carried out in compliance with WHO 2010 guidelines, comparing every study population semen variable to the WHO 2021 reference group (n~3500). Results: All evaluated semen parameters had median values that fell within a normal range. Nonetheless, approximately 25% of patients had values for each semen variable that were lower than the WHO reference group's fifth percentile. In particular, bacteriospermia was associated with a negative impact on semen volume. Conclusions: This is the largest study that compares all standard semen parameters in patients suffering from CP/CPPS to WHO 2021 reference values. It provides evidence of an impairment of conventional semen parameters.

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

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

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

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

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.

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

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

Bacillus Calmette-Guérin (BCG) prostato-epididymitis in a patient treated for a non-invasive urothelial cancer: A case report.

Introduction: The Bacillus Calmette-Guérin (BCG) used as anti-tuberculous vaccine is also a well-known therapy for superficial urothelial cancer. Local or general side effects can occur, although it is generally well tolerated. Case: We present the case of a 65 year-old caucasian man consulting for gross hematuria and lower urinary tract symptoms. Magnetic resonance imaging (MRI) demonstrated a non-invasive urothelial carcinoma (NMIBC) and Prostate Imaging-Reporting and Data System (PIRADS) IV lesions. Transurethral resection of the bladder tumor revealed a non-invasive transitional cell carcinoma. Intravesical Bacillus Calmette Guerin (BCG) therapy was provided. After 6 intravesical instillations, the patient presented with prostato-epididymitis. Forthcoming BCG instillations were canceled, and cancer treatment was switched to epirubicine. Treatment with ethambutol, rifampicin and isoniazid was started with rapid resolution of the symptoms. Urinary and semen cultures grew Mycobacterium tuberculosis complex strain BCG. As prostate specific antigen (PSA) rose, prostate's biopsies were performed showing extensive necrosis boarded by granulomas without signs of malignancy. Discussion: BCGitis is a rare complication in patients treated for non-invasive urothelial cancer. Several risk factors, local and systemic, should be considered prior to this immunotherapy. BCGitis (local or disseminated) or hypersensitivity reactions to BCG must be included in the differential diagnosis even if therapy was administered several years before the symptoms. Adequate treatment must be started as fast as possible to avoid serious complications.

Pubourethral and uterosacral male analogues suggest parallel male/female pelvic anatomy and symptom pathogenesis.

The thesis that functional/dysfunctional male/female pelvic floor anatomy are parallel, originated from two studies: a successful retropubic perineal male sling for post-prostatectomy stress urinary incontinence (SUI) and discovery of a male uterosacral ligament (USL) analogue, we named "prostatosacral ligament" (PSL). In 25 out of the studied 27 males (92.6%), it starts on both sides of the median sulcus of the prostate the ligament passes lateral to the rectum being fused with the lateral margin of the mesorectum before leaving it as it thins out to be attached posteriorly similar to the USL. The ultrasound data during straining in men and women showed the same three oppositely acting muscle vectors contracting around analogous ligaments, puboprostatic ligament (PPL) (male), and pubourethral ligament (PUL) (female). Further parallels were pubovesical ligaments (PVLs) and arc of Gilvernet as part of the continence and micturition mechanisms. Impressive evidence for parallel anatomy came from the successful cure of 22 males with post-prostatectomy SUI using a perineal retropubic tissue fixation system (TFS) minisling applied to the PPL using a similar methodology to that used in the female for PUL midurethral sling repair for cure of SUI. Laparoscopic evidence confirmed the prostate as a male analogue of the cervix, and PSLs as analogues of USLs: PSL origin from the prostate attached laterally to the mesorectum and inserted into the sacrum. Histologically, PSLs had identical features with USLs: collagen, elastin, smooth muscle, blood vessels and nerves. Virtually identical symptoms for "chronic prostatitis" (CP) and "posterior fornix syndrome" (PFS), such as chronic pelvic pain, overactive bladder (OAB), abnormal emptying, gave birth to the hypothesis, of a common pathogenesis for "CP" and "PFS", USL (or PSL) laxity. If this could be proven by "simulated operations", "CP", at least in theory, may be potentially correctible by PSL repair.

Network pharmacology and in vivo experiment-based strategy for investigating the mechanism of chronic prostatitis/chronic pelvic pain syndrome in QianLieJinDan tablets.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common urinary system disease that is prone to recurrence. It typically leads to varying degrees of pelvic pain and discomfort, as well as symptoms related to the urinary system in affected patients. QianLieJinDan tablets (QLJD), a traditional Chinese medicine, have shown promising therapeutic effects on CP/CPPS in clinical practice, but the underlying mechanisms of QLJD in treating CP/CPPS have not been determined. Objective: To reveal the phytochemical characterization and multitarget mechanism of QLJD on CP/CPPS. Methods: The concentrations of the components of QLJD were determined using UHPLC-Q Exactive Orbitrap-MS. Utilizing network pharmacology approaches, the potential components, targets, and pathways involved in the treatment of CP/CPPS caused by QLJD were screened. Molecular docking calculations were employed to assess the affinity between the components of the QLJD and potential targets, revealing the optimal molecular conformation and binding site. Finally, the therapeutic efficacy and potential underlying mechanisms of QLJD were investigated through pharmacological experiments. Results: In this study, a total of 35 components targeting 29 CP-related genes were identified, among which quercetin, baicalin, icariin, luteolin, and gallic acid were the major constituents. Enrichment analysis revealed that the potential targets were involved mainly in the regulation of cytokines, cell proliferation and apoptosis, and the oxidative stress response and were primarily associated with the cytokine‒cytokine receptor interaction pathway, the IL-17 signaling pathway, the Th17 cell differentiation pathway, and the JAK-STAT signaling pathway. In vivo experiments demonstrated that QLJD effectively attenuated the infiltration of CD3+ T cells and the expression of ROS in a CP/CPPS model rat prostate tissue. Furthermore, through the inhibition of IL-6 and STAT3 expression, QLJD reduced the differentiation of Th17 cells, thereby ameliorating pathological injury and prostatic index in prostate tissue. Conclusion: The potential of QLJD as an anti-CP/CPPS agent lies in its ability to interfere with the expression of IL-6 and STAT3, inhibit Th17 cell differentiation, reduce inflammatory cell infiltration in rat prostate tissue, and alleviate oxidative stress damage through its multi-component, multi-target, and multi-pathway effects.

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis.

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1ß, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

[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.

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.

Causal effect of gut microbiota on the risk of prostatitis: a two-sample Mendelian randomization study.

BACKGROUND: Recent studies demonstrated that chronic prostatitis (CP) is closely related to the gut microbiota (GM). Nevertheless, the causal relationship between GM and CP has not been fully elucidated. Therefore, the two-sample Mendelian randomization (MR) analysis was employed to investigate this association. METHODS: The summary data of gut microbiota derived from a genome-wide association study (GWAS) involving 18,340 individuals in the MiBioGen study served as the exposure, and the corresponding summary statistics for CP risk, representing the outcome, were obtained from the FinnGen databases (R9). The causal effects between GM and CP were estimated using the inverse-variance weighted (IVW) method supplemented with MR-Egger, weighted median, weighted mode, and simple mode methods. Additionally, the false discovery rate (FDR) correction was performed to adjust results. The detection and quantification of heterogeneity and pleiotropy were accomplished through the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression. RESULTS: The IVW estimates indicated that a total of 11 GM taxa were related to the risk of CP. Seven of them was correlated with an increased risk of CP, while the remained linked with a decreased risk of CP. However, only Methanobacteria (OR 0.86; 95% CI 0.74-0.99), Methanobacteriales (OR 0.86; 95% CI 0.74-0.99), NB1n (OR 1.16; 95% CI 1.16-1.34), Methanobacteriaceae (OR 0.86; 95% CI 0.74-0.99), Odoribactergenus Odoribacter (OR 1.43; 95% CI 1.05-1.94), and Sutterellagenus Sutterella (OR 1.33; 95% CI 1.01-1.76) still maintain significant association with CP after FDR correction. Consistent directional effects for all analyses were observed in the supplementary methods. Subsequently, sensitivity analyses indicated the absence of heterogeneity, directional pleiotropy, or outliers concerning the causal effect of specific gut microbiota on CP (p > 0.05). CONCLUSION: Our study demonstrated a gut microbiota-prostate axis, offering crucial data supporting the promising use of the GM as a candidate target for CP prevention, diagnosis, and treatment. There is a necessity for randomized controlled trials to validate the protective effect of the linked GM against the risk of CP, and to further investigate the underlying mechanisms involved.

Knockout of phosphatidylethanolamine binding protein4 (PEBP4) promotes chronic non-bacterial prostatitis by mediating the activation of NF-κB signaling.

BACKGROUND: The etiology of chronic prostatitis remains unclear; consequently, this disease is associated with recurrence and ineffective clinical therapy. Therefore, there is an urgent need to investigate the underlying pathogenesis of chronic prostatitis in order to develop more efficacious treatments. OBJECTIVE: The previous study found that knocking out of PEBP4 leads to chronic prostatitis in the male mice. This research aimed to identify the role of PEBP4 in prostatitis, determine the molecular pathogenic mechanisms associated with chronic prostatitis, and provide guidelines for the development of new treatment strategies for chronic prostatitis. MATERIALS AND METHODS: A PEBP4 exon knockout strain (PEBP4-/-) was established in C57BL/6 mice via the Cre-loxP system. Hematoxylin-eosin (H&E) staining was used to investigate histological changes. RNA-sequencing was used to investigate the gene expression signature of the prostate and the levels of inflammatory cytokines were determined by real-time polymerase chain reaction (RT-PCR). The expression of PEBP4 protein in prostate tissue was determined by immunohistochemistry in specimens from patients with BPH and BPH combined with chronic prostatitis. Finally, we used a CRISPR-Cas9 plasmid to knockout PEBP4 in RWPE-1 cells; western blotting was subsequently used to measure the level of activation in the NF-κB signaling pathway after activating with TNF-α. RESULTS: Hemorrhage and inflammatory cell infiltration were incidentally observed in the seminal vesicles and prostate glands of PEBP4-/- mice after being fed with a normal diet for 1 year. In addition, we found significantly lower (p < 0.001) expression levels of PEBP4 protein in prostate tissues from patients with benign prostate hyperplasia (BPH) and chronic and non-bacterial prostatitis (CNP) when compared to those with BPH only. The reduced expression of PEBP4 led to a higher risk of prostatitis recurrence in patients after 2 years of follow-up. Increased levels of NF-κB and IκB phosphorylation were observed in PEBP4-knockout RWPE-1 cells and prostate glands from PEBP4-/- mice. CONCLUSION: The knockout of PEBP4 in experimental mice led to chronic prostatitis and the reduced expression of PEBP4 in patients with higher risk of chronic and non-bacterial prostatitis suggested that PEBP4 might act as a protective factor against chronic prostatitis. The knockout of PEBP4 in RWPE-1 cells led to the increased activation of NF-κB and IκB, thus indicating that inhibition of PEBP4 faciliated the NF-κB signaling cascade. Our findings provide a new etiology and therapeutic target for chronic prostatitis.

[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.

The role of multiparametric magnetic resonance imaging in the diagnosis of granulomatous prostatitis mimicking prostate cancer.

PURPOSE: Aimed to investigate the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis of granulomatous prostatitis caused by intravesical Bacillus Calmette-Guérin (BCG). METHODS: In this prospective, single-center study, 10 male patients who were given intravesical BCG due to intermediate- and high-risk bladder cancer were included. Before transurethral resection of bladder tumors (TURB), all patients were evaluated by mp-MRI, serum prostate-specific antigen (PSA), and digital rectal examination (DRE). Serum PSA levels and DRE findings were evaluated before and after intravesical BCG treatment. Prostate mp-MRI was performed for patients with elevated levels of serum PSA and/or with abnormal DRE findings. Then, MRI fusion + systematic prostate biopsy was performed. Demographic data of the patients before and after intravesical BCG were compared. RESULTS: The average age of the patients was 66.9 years (55-87 years). While PSA was 1.7 ng/ml before intravesical BCG treatment, it was 4.3 ng/ml after intravesical BCG treatment (p = 0.005). PSA density (PSAD) was 0.04 and 0.10 before and after the treatment, respectively (p = 0.012). DRE findings of all patients were normal before the treatment. However, abnormal findings were detected in 80% of them after the treatment (p = 0.008). PI-RADS ≥ 3 lesions were found to be significantly higher in all patients after intravesical BCG (p = 0.004). CONCLUSION: Granulomatous prostatitis is a rare complication of intravesical BCG. High PSA, abnormal DRE, and PI-RADS ≥ 3 lesions detected after intravesical BCG should suggest granulomatous prostatitis and unnecessary biopsies may be avoided.

Genetic insights into gut microbiota and risk of prostatitis: a Mendelian randomization study.

Background: The dysbiosis of gut microbiota (GM) is considered a contributing factor to prostatitis, yet the causality remains incompletely understood. Methods: The genome-wide association study (GWAS) data for GM and prostatitis were sourced from MiBioGen and FinnGen R10, respectively. In the two-sample Mendelian randomization (MR) analysis, inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, weighted mode, and maximum likelihood (ML) methods were utilized to investigate the causal relationship between GM and prostatitis. A series of sensitivity analysis were conducted to confirm the robustness of the main results obtained from the MR analysis. Results: According to the IVW results, genus Sutterella (OR: 1.37, 95% CI: 1.09-1.71, p = 0.006) and genus Holdemania (OR: 1.21, 95% CI: 1.02-1.43, p = 0.028) were associated with an increased risk of prostatitis. The phylum Verrucomicrobia (OR: 0.76, 95% CI: 0.58-0.98, p = 0.033) and genus Parasutterella (OR: 0.84, 95% CI: 0.70-1.00, p = 0.045) exhibited a negative association with prostatitis, indicating a potential protective effect. Sensitivity analysis showed that these results were not affected by heterogeneity and horizontal pleiotropy. Furthermore, the majority of statistical methods yielded results consistent with those of the IVW analysis. Conclusions: In this study, we identified two GM taxon that might be protective against prostatitis and two GM taxon that could increase the risk of developing prostatitis. These findings could potentially provide a valuable theoretical basis for the future development of preventive and therapeutic strategies for prostatitis.

Cannabidiol Alleviates Chronic Prostatitis and Chronic Pelvic Pain Syndrome via CB2 Receptor Activation and TRPV1 Desensitization.

PURPOSE: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17ß-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague-Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17ß-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. RESULTS: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. CONCLUSIONS: CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Non-Invasive Radiofrequency Hyperthermia Attenuates HMGB1/TLR4/NF-κB Inflammatory Axis in a Chronic Prostatitis/Chronic Pelvic Pain Syndrome Rat Model.

PURPOSE: The primary goal of this study is to evaluate the effect of the non-invasive radiofrequency hyperthermia (RFHT) device on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) rat model and investigate the underlying mechanism. MATERIALS AND METHODS: In this study, Sprague-Dawley rats were randomly distributed into three groups: (1) normal control group, (2) CP/CPPS group, and (3) RFHT group. CP/CPPS rat models were induced by 17ß-estradiol and dihydrotestosterone for 4 weeks and RFHT was administered for 5 weeks after model establishment. During RFHT administration, core body temperatures were continuously monitored with a rectal probe. After administering RFHT, we assessed pain index for all groups and collected prostate tissues for Western blot analysis, immunofluorescence, and immunohistochemistry. We also collected adjacent organs to the prostate including urinary bladder, testes, and rectum for safety assessment via H&E staining along with a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay. RESULTS: After administering RFHT, pain in rats was significantly alleviated compared to the CP/CPPS group. RFHT reduced high-mobility group box 1 (HMGB1) expression and improved inflammation by downregulating subsequent proinflammatory cytokines through inhibition of the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. In prostate-adjacent organs, no significant histological alteration or inflammatory infiltration was detected. The area of cell death also did not increase significantly after RFHT. CONCLUSIONS: In conclusion, RFHT demonstrated anti-inflammatory effects by inhibiting the HMGB1-TLR4-NF-κB pathway in CP/CPPS rat models. This suggests that RFHT could serve as a safe and promising therapeutic strategy for CP/CPPS.