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.

CD8 T cells are dispensable for experimental autoimmune prostatitis induction and chronic pelvic pain development.

Introduction: Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied. Methods: We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals. Results: We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions. Discussion: Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.

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.

[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.

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.

Involvement of NOTCH1-mediated Microglia Activation in Neuromodulation of Chronic Prostatitis-related Pain.

BACKGROUND/AIM: This study aimed to investigate the role of NOTCH receptor 1 (NOTCH1)-mediated activation of microglia in the L5-S2 spinal dorsal horn in chronic prostatitis pain. MATERIALS AND METHODS: Rats were divided into chronic prostatitis (CP) group and control group. Complete Freund's adjuvant was injected into the prostate, and prostate pathology and pain-related behavior were monitored to assess the successful establishment of the CP-related pain model. The dorsal horn of the L5-S2 spinal cord was collected for the detection of ionized calcium-binding adapter molecule 1 (IBA-1) and NOTCH1 expression by quantitative real time polymerase chain reaction and the detection of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) by enzyme-linked immunosorbent assay. Electrical excitability was assessed with whole-cell patch clamp. In addition, NOTCH1 receptor inhibitor or inhibitor of microglial cell activation was injected into the subarachnoid space, and the pro-inflammatory cytokines in the spinal cord were detected. RESULTS: In the CP group, the expression of NOTCH1, IBA-1, TNF-α and IL-1ß began to increase at 4 days, peaked at 12 days, and began to decline at 24 days, and it was significantly higher than in the control group (p<0.01). Inhibition of microglia or NOTCH1 receptor markedly reduced the content of TNF-α and IL-1ß in the spinal cord (p<0.05). At 4, 12 and 24 days, the amplitude and frequency of neuronal action potential increased and the threshold decreased markedly as compared to the control group (p<0.05), and spontaneous action potential was noted. CONCLUSION: NOTCH1 mediates the activation of microglia in the L5-S2 spinal cord, leading to the secretion of inflammatory factors and enhanced electrical excitability of neurons, which is related to persistent and refractory chronic prostatitis-related pain.

Granulomatous prostatitis: mimicking locally advanced prostate adenocarcinoma.

We report the case of a 63-year-old male who came to the urology clinic with an increasing value of the prostate specific antigen and an asymmetrical enlargement at the digital rectal examination. The man was subjected to an MRI of the prostate following which a convincing radiological diagnosis of prostate cancer was made. The patient was assigned a provisional stage of disease T3a N0. In order to confirm this diagnosis, a prostate biopsy was performed but the histological analysis reported non-specific granulomatous prostatitis (GP). It is an uncommon condition that both clinically and radiologically on TRUS and MRI usually mimics prostate cancer (PCa), representing a diagnostic challenge due to its non-specific symptoms and aspecific radiological findings. In this case report we discuss the magnetic resonance imaging features of this rare clinical condition in order to help radiologists in the timely diagnosis for a correct diagnostic framing.

Prostatic proliferative inflammatory atrophy: welcome to the club†.

Single-cell RNA sequencing studies in the human prostate have defined a population of epithelial cells with transcriptional similarities to club cells in the lung. However, the localization of club-like cells in the human prostate, and their relationship to prostate cancer, is poorly understood. In a new article in The Journal of Pathology, RNA in situ hybridization was used to demonstrate that club cell markers are expressed in luminal cells adjacent to inflammation in the peripheral zone of the human prostate, where prostate cancer tends to arise. These club-like cells are commonly found in proliferative inflammatory atrophy (PIA) lesions and express markers consistent with an intermediate epithelial cell-type. Future studies will be needed to understand the functional role of club-like cells in human prostate inflammation, regeneration, and disease. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Automatic detection of prostate cancer grades and chronic prostatitis in biparametric MRI.

BACKGROUND AND OBJECTIVE: With emerging evidence to improve prostate cancer (PCa) screening, multiparametric magnetic prostate imaging is becoming an essential noninvasive component of the diagnostic routine. Computer-aided diagnostic (CAD) tools powered by deep learning can help radiologists interpret multiple volumetric images. In this work, our objective was to examine promising methods recently proposed in the multigrade prostate cancer detection task and to suggest practical considerations regarding model training in this context. METHODS: We collected 1647 fine-grained biopsy-confirmed findings, including Gleason scores and prostatitis, to form a training dataset. In our experimental framework for lesion detection, all models utilized 3D nnU-Net architecture that accounts for anisotropy in the MRI data. First, we explore an optimal range of b-values for diffusion-weighted imaging (DWI) modality and its effect on the detection of clinically significant prostate cancer (csPCa) and prostatitis using deep learning, as the optimal range is not yet clearly defined in this domain. Next, we propose a simulated multimodal shift as a data augmentation technique to compensate for the multimodal shift present in the data. Third, we study the effect of incorporating the prostatitis class alongside cancer-related findings at three different granularities of the prostate cancer class (coarse, medium, and fine) and its impact on the detection rate of the target csPCa. Furthermore, ordinal and one-hot encoded (OHE) output formulations were tested. RESULTS: An optimal model configuration with fine class granularity (prostatitis included) and OHE has scored the lesion-wise partial Free-Response Receiver Operating Characteristic (FROC) area under the curve (AUC) of 1.94 (CI 95%: 1.76-2.11) and patient-wise ROC AUC of 0.874 (CI 95%: 0.793-0.938) in the detection of csPCa. Inclusion of the auxiliary prostatitis class has demonstrated a stable relative improvement in specificity at a false positive rate (FPR) of 1.0 per patient, with an increase of 3%, 7%, and 4% for coarse, medium, and fine class granularities. CONCLUSIONS: This paper examines several configurations for model training in the biparametric MRI setup and proposes optimal value ranges. It also shows that the fine-grained class configuration, including prostatitis, is beneficial for detecting csPCa. The ability to detect prostatitis in all low-risk cancer lesions suggests the potential to improve the quality of the early diagnosis of prostate diseases. It also implies an improved interpretability of the results by the radiologist.

Strong PD-L1 expression in granulomatous prostatitis.

BACKGROUND: The expression of programmed cell death ligand protein (PD-L1) is weakly investigated in non-tumoral and inflammatory prostatic pathology. The diagnosis of granulomatous prostatitis (GP) rests on the recognition of localized or diffuse epithelioid granulomatous inflammation in prostatic tissue which is frequently difficult by conventional histological observation alone. PD-L1 expression in GP is not well studied so far. METHODS: We studied PD-L1 expression in 17 GP cases (9 nonspecific GP, 5 Bacillus Calmette-Guérin induced prostatitis, 1 prostatic tuberculosis, and 3 cases of postsurgical prostatic granulomas). The control group included 10 radical prostatectomies of patients with high Gleason score prostate adenocarcinoma (PCa) and National Institutes of Health-category IV prostatitis (high-grade histologic prostatitis; HG-HP). RESULTS: All of the GP cases showed easily visible strong membranous PD-L1 expression (high levels of combined positive score) in localized and diffuse epithelioid granulomatous prostatic inflammation. None of the control cases showed the presence of significant PD-L1 expression in inflammatory infiltrates in HG-HP, tumor parenchyma, and stroma in PCa. CONCLUSIONS: The study presents the first attempt to examine PD-L1 expression in GP. Granulomatous inflammation in GP is easily identified when stained with PD-L1.

Inflammatory response to Trichomonas vaginalis in the pathogenesis of prostatitis and benign prostatic hyperplasia.

Trichomonas vaginalis is a flagellated protozoan that causes trichomoniasis, a common nonviral sexually transmitted infection. T. vaginalis infection is asymptomatic in most infected men but can lead to chronic infection. The inflammatory response to chronic T. vaginalis infection may contribute to prostatic diseases, such as prostatitis and benign prostatic hyperplasia (BPH); however, studies on the relationship between T. vaginalis infection and prostate diseases are scarce. In this review, we discuss evidence from our studies on the involvement of T. vaginalis in the pathogenesis of prostate diseases, such as prostatitis and BPH. Studies of prostatitis have demonstrated that the attachment of T. vaginalis trophozoite to prostate epithelial cells (PECs) induces inflammatory cytokine production and inflammatory cell migration, leading to prostatitis. T. vaginalis also causes pathological changes, such as inflammatory cell infiltration, acinar changes, interstitial fibrosis, and mast cell infiltration, in prostate tissues of infected rats. Thus, T. vaginalis is considered an infectious agent that triggers prostatitis. Meanwhile, studies of prostatic hyperplasia revealed that mast cells activated by T. vaginalis-infected prostate cells secreted inflammatory mediators, such as ß-hexosaminidase and tryptase, which promoted proliferation of prostate stromal cell (PSC). Moreover, interleukin-6 produced by proliferating PSCs induced the multiplication of BPH-1 epithelial cells as a result of stromal-epithelial interaction, suggesting that the proliferation of T. vaginalis-infected prostate cells can be induced through crosstalk with mast cells. These collective findings suggest that T. vaginalis contributes to the progression of prostatitis and prostatic hyperplasia by creating an inflammatory microenvironment involving PECs and PSCs.

Complication rates of transrectal and transperineal prostate fusion biopsies - is there a learning curve even in high volume interventional center?

PURPOSE: To analyze the learning curve regarding complication rates of transrectal prostate biopsy (TRPB) versus transperineal prostate biopsy (TPPB), using real time software-based magnetic resonance imaging ultrasound (MRI-US) fusion techniques, along with first year experience of transperineal approach. MATERIALS AND METHODS: retrospective unicentric cohort study at a quaternary care hospital. Medical records of all consecutive patients that underwent TPPB between March 2021 and February 2022, after the introduction of MRI-US fusion device, and those who underwent TRPB throughout the entire years of 2019 and 2020 were analyzed. All complications that occurred as consequences of the procedure were considered. Descriptive statistics, Chi-squared and Fisher tests were used to describe complications and compare the two groups. RESULTS: A total of 283 patients were included in the transperineal group and 513 in the transrectal group. The analysis of a learning curve for the transperineal method showed lower complications rates comparing the first six months of TPPB procedures (group 1); The complication rate for TPPB was lower than that of TRPB (55.1% versus 81.9%, respectively; p<0.01). TPPB showed specifically lower rates of hematuria (48.8% versus 66.3%;p<0.001) and rectal bleeding(3.5% versus 18.1%; p<0.001). There were no cases of prostatitis after transperineal biopsies and three cases (0.6%) after transrectal procedures. CONCLUSIONS: We evidenced the learning curve for performing the transperineal biopsy, with a lower rate of complications for the experienced team, after 142 cases after 6 months of practice. The lower complication rate of TPPB and the absence of infectious prostatitis imply a safer procedure when compared to TRPB.

Does histological prostatic inflammation during transurethral resection of the prostate for bladder outlet obstruction affect post-operative urinary outcomes?

OBJECTIVE: Benign prostate hyperplasia (BPH) is a common cause for bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS) in men. The pathophysiology of BPH is multifactorial and inflammation has been linked with progression of BPH and LUTS. The association between histological prostatitis found at transurethral resection of the prostate (TURP) and adverse post-operative urinary outcomes is not clearly defined. Our aim was to evaluate the association between histological prostatitis and adverse post-operative urinary outcomes following TURP procedure. METHODS: Patients who had undergone TURP for BPH at a single institution between 2014 and 2018 were included. The study population was divided into three cohorts: those with no histological inflammation, those with any form of inflammation and those specifically with prostatic stromal inflammation. Functional outcomes were assessed by defining a series of measurable post-operative "LUTS events" and comparing these to time-to-event profile using a Kaplan-Meier estimator. RESULTS: A total 198 patients were included (no inflammation n = 101; any inflammation n = 97, prostatic stromal inflammation n = 81). All three groups were comparable in terms of baseline characteristics. The any inflammation group had significantly more adverse post-operative outcomes after TURP compared to the no inflammation group, P = 0.0065. The stromal inflammation group had more LUTS events after surgery compared to the no inflammation groups in the first year of follow-up n = 0.011; over a 5-year follow-up period the results were not statistically significant, P = 0.244. CONCLUSION: Histological prostatitis is associated with worse urinary outcomes after TURP compared to no inflammation. These results are useful in improving prognostic discussions with patients after TURP.

Nutritional and surgical aspects in prostate disorders.

Prostate disorders are commonplace in medicine, especially in older men, with prostatitis, benign prostatic hyperplasia, and prostate cancer being the most abundant pathologies. The complexity of this organ, however, turns treatment into a challenge. In this review, we aim to provide insight into the efficacy of alternative treatments, which are not normally used in conventional medicine, with a particular focus on nutrients. In order to understand why and how nutrition can be beneficial in diseases of the prostate, we give an overview of the known characteristics and features of this organ. Then, we provide a summary of the most prevalent prostate illnesses. Finally, we propose nutrition-based treatment in each of these prostate problems, based on in-depth research concerning its effects in this context, with an emphasis on surgery. Overall, we plead for an upgrade of this form of alternative treatment to a fully recognized mode of therapy for the prostate.

Candida prostatitis: A rare entity.

Prostatitis may present with lower urinary tract symptoms (LUTS) attributable to acute and chronic bacterial infections (NIH Category I/II) or as asymptomatic inflammatory prostatitis (NIH Category IV). Patients with chronic prostatitis/chronic pelvic pain syndrome, (CP/CPPS, NIH Category III) may present with a wide range of symptoms resulting from varied etiology, however, seldom caused by fungal infections. Occasional case reports have been published on prostatitis due to Candida sp. We report a case of an elderly diabetic patient who underwent perurethral prostatic resection (TURP) for benign prostatic hyperplasia (BPH) and returned with complaints of LUTS and perineal discomfort one month later. After repeat surgery, the TURP chips on histopathology showed features of prostate hyperplasia and prostatitis with numerous hyphae and yeast forms of Candida admixed with acute and chronic inflammatory exudate. After confirmation by special stains and positive urine culture, a final diagnosis of prostatic candidiasis was made.

[Research on the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis].

Objective： To explore the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis. Methods: The rat model of chronic abacterial prostatitis was induced by stimulation with 2% sterile carrageenan solution. After modeling, the rats were randomly divided into two groups, Model control group (Model group) and oxalis group. Another normal control group was set up. The rats in the Model group and the normal control group were given 0.01ml/g normal saline by gavage, and the rats in the oxalis alis group were given 1ml/100g (1 g/kg) of Oxalis corniculata L warm water decoction by gavage once a day for 28 days. Twenty-four hours after the last administration, 10ml blood was collected from the abdominal aorta of the rats, and prostate tissue samples were collected from the rats. hematoxylin-eosin (HE) staining was used to observe the morphological structure of the prostate in normal and prostatitis rats. ELISA was used to detect the levels of serum and prostate cytokines. The protein expressions of 4-HNE , ALDH2 and FGF2 were detected by Western blot. Results: Compared with the blank group, the model group showed obvious hyperplasia of fibrous tissue in the interstitium of the prostate tissue, disordered glandular structure, papillary hyperplasia of epithelial cells in the acini, infiltration of a small amount of lymphocytes, monocytes and other inflammatory cells in the acini, and increased pathological scores. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 in prostate tissue were significantly increased. Compared with the model group, the prostate tissue of the oxalis group was slightly damaged, with a small amount of fibrous hyperplasia and inflammatory cell infiltration. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 were decreased in prostate tissue. Conclusion： Oxalis corniculata L can effectively repair the pathological morphology of prostate tissue in rats with CNP, and its mechanism may be related to activating 4-HNE protein and reducing oxidative stress injury of prostate tissue in rats.

[Long-term inflammatory and neoplastic reaction of prostate tissues during its transurethral infection with uropathogens: evaluation of the results of animal model study].

INTRODUCTION: There is no convincing evidence of the persistence of acute or the development of chronic bacterial-induced prostatic inflammation in the long term when infected with various titers of the uropathogen. Along with this, controversial data are presented on the relationship between post-infectious chronic inflammation and neoplastic changes in prostate tissues. OBJECTIVE: To carry out, based on the experimental data: 1) assessment of the degree of bacterial contamination and the severity of histological changes in prostate tissues on the 60th follow-up day in case of transurethral infection with various uropathogens in titers of 102,3,5 CFU/ml; 2) fundamental comparative analysis between the indicators of the inoculated test-titer and microbial load with the severity of histological changes in prostate tissues; 3) verification of neoplastic transformations in the prostate tissues during a long-term persistent bacterial-induced inflammatory process. MATERIALS AND METHODS: Animal studies were conducted using FELASA protocols. Laboratory animals: 14 New Zealand rabbits. Tested uropathogens: aerobes - E. coli, S. haemolyticus, anaerobes - P. niger. Titers: 102,3,5 CFU/ml. Uropathogen inoculation technique: topical transurethral. RANDOMIZATION: all laboratory animals were divided into 5 groups according to the uropathogen (4 experimental, 1 control). Follow-up period: 60 days. Sacrification and autopsy of the animals were performed on day 60. Biopsies were taken from various parts of the prostate, as well as from the bladder neck and the edge of the membranous urethra. Cultural, histological and immunohistochemical (expression of p53 and Ki-67) studies of prostate tissues were conducted. Statistical data processing was performed using the GraphPad Prism 9.0 program (GraphPad Software Inc., Graphpad Holdings LLC, San Diego, CA, USA) applying descriptive and non-parametric statistics. RESULTS: Two individuals infected with S. haemolyticus + P. niger had a lethal outcome. The contamination of prostate tissue was determined in all cases of infection. In 88.9% of the cases, an increase in tissue microbial load was determined compared to the initial titer. Multivariate analysis of culture study values revealed the presence of intragroup differences in prostate contamination only between infection with E. coli 103 CFU/ml and E. coli 105 CFU/ml (p=0.006), as well as intergroup differences between infection with E. coli 105 CFU/ml and P. niger 105 CFU/ml (p=0.013). The histological study revealed moderate proliferative inflammation after inoculation with 102,3,5 CFU/ml in the E. coli and S. haemolyticus groups. In the case of S. haemolyticus, it was more pronounced due to the presence of persistent alterative lesion foci; in the P. niger group, mild proliferative transformations were observed in prostate tissues in all cases. The immunohistochemical study of changes determined p53 expression (10.0%) in some areas of the glandular epithelium of prostate glands (but without a positive internal control) only in case of infection with E. coli 105 CFU/ml. Areas of glandular epithelium with Ki-67 expression ( less or equal 25.0%) were visualized in all tested groups, mainly at titers of 103 and 105 CFU/ml, but the severity of proliferative activity was not high (1+). There were no foci of prostate tissue with simultaneous nuclear activity of p53 and Ki-67. CONCLUSION: Proliferative inflammation of different intensity in prostate tissues was observed after sixty days. Its severity was mainly determined by the type of infecting agent (S. haemolyticus > E. coli > P. niger) and was not dependent on the inoculated titer and the subsequent microbial load of prostate tissues. No areas of neoplastic transformation of prostate tissues were reliably identified in the case of a bacterial-induced inflammatory process in the estimated follow-up period.

Abnormal prostate microbiota composition is associated with experimental autoimmune prostatitis complicated with depression in rats.

Background: Microbiota play essential roles in the pathogenesis of prostatitis and depression. However, the changes in prostate microbiota have not yet been explored in rats with prostatitis/depression. This study aimed to investigate the changes of prostate microbiota in rats with prostatitis/depression. Methods: Rats with experimental autoimmune prostatitis (EAP) complicated with depression were constructed through injection of rat prostate antigen with immunoadjuvants followed by application of chronic unpredictable mild stress (CUMS). The rats were subjected to inflammatory factor detection and behavioral testing to confirm the establishment of the model. Subsequently, the prostate microbiota was assayed in the rats and compared by 16S rRNA gene sequencing. Results: A rat model of EAP complicated with depression was established and confirmed by increases in IL-1ß, IL-6, and TNF-α as well as the occurrence of depressive-like behaviors. EAP/CUMS significantly altered the richness, evenness, and composition of prostate microbiota. Forty-six taxonomic biomarkers for prostate microbiota were enriched in rats with EAP/depression and exhibited statistically significant and biologically consistent differences. Metabolomics profiling revealed that EAP/depression was associated with reductive acetyl coenzyme A pathway, L-lysine fermentation to acetate and butanoate, protein N-glycosylation and purine nucleobases degradation I, which is regulated by DCE29, Nocardioes, Helicobacter and Dorea. Conclusion: Findings from the study demonstrate the existence of abnormal prostate microbiota in EAP complicated with depression and may be helpful in the treatment of comorbid diseases of prostatitis and depression.

Positive urine culture prior to transrectal prostate biopsy was not associated with infectious complications development.

OBJECTIVE: Prostate cancer is one of the most common cancers worldwide. Its histological diagnosis is based on prostate biopsy. The transrectal procedure is one of the most common procedures performed by urologists. Although it is considered safe, post-biopsy infectious complications are frequently observed in practice. The aim of this study is to investigate the value of urine culture before the transrectal biopsy. Secondly, we assessed potential risk factors for infectious complications following TR-PB. METHODS: We performed a retrospective analysis of all patients who underwent urine culture tests before transrectal prostate biopsy between January 2019 and July 2020. The inclusion criteria for the study were all indications for prostate biopsy (PSA>4ng/mL or abnormal digital rectal examination). Baseline characteristics and the incidence of post-biopsy urinary tract infection were compared between patients showing positive pre-biopsy culture results and those showing negative findings. Multivariate logistic regression analyses were used to determine risk factors for infectious complications following TR-PB. RESULTS: Out of 163 patients included in our study, 19 patients (11.65%) had positive urine culture results before the biopsy. Age (P=0.068); history of hospitalization (P>0.999), history previous of quinolone use (P=0.75), history of UTI (P=0.64); median PSA level at diagnosis (P=0.267); prostate volume (P=0.78); post-void residual volume (P=0.374); percentage of patients testing positive for cancer on biopsy (P=0.81); and percentages of patients with a history of biopsy (P=0.889), diabetes mellitus (P=0.524), hypertension (P=0.714) and immunosuppressive medication use (P>0.999) were similar between the two groups. One patient in the positive urine culture group had post-biopsy prostatitis. However, 3.24% (five patients) of the negative urine culture group had the disease (P=0.789) (four patients with prostatitis and one with epididymitis). Among them, four patients were diagnosed by urine culture at the time of post-biopsy urinary tract infection. Multivariate logistic regression analysis demonstrated that history of hospitalization and history of previous quinolone use were risk factors for infection after transrectal prostate biopsy. CONCLUSION: Our study suggests that systematically performing urine cultures before transrectal prostate biopsy does not reduce the rate of infectious complications after biopsy. Positive pre-biopsy cultures were not associated with the development of post-biopsy infectious complications.

PD-L1 positive lympho-epithelial lesions in inflammatory prostate.

OBJECTIVES: Ductal epithelial changes (lympho-epithelial lesions-LEL) in prostatic chronic inflammation (CI) are not well studied so far. AIM: to investigate LEL immediately adjacent to prostatic CI. METHODS: We studied LEL in 144 prostatic surgical and autopsy specimens in various types of prostatic CI: NIH-category IV prostatitis (histologic prostatitis-HP), nonspecific granulomatous prostatitis (NSGP), and the reactive lymphoid infiltrates in the vicinity of benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCa). CI is scored as low and high grade (LG, HG) according to the severity of inflammation. RESULTS: LEL was identified in all types of prostatic specimens and in all types of prostatic CI: in 70.9% of patients with HP; in 100% of cases with NSGP; in 68.7% and in 80% adjacent to BPH and PCa respectively. Statistical analysis showed a significant correlation of the presence of LEL with HG CI (p<0.001). LEL showed strong membranous PD-L1 expression. CONCLUSIONS: The study presents the first attempt to examine LEL in inflammatory human prostate. PD-L1 positive LEL have no diagnostic organ specificity, although they are a constant histological finding in HG prostatic CI. LEL, inducible after birth by CI, are an integral part of prostate-associated lymphoid tissue (PALT) and of the inflammatory prostatic microenvironment.