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BACKGROUND: The complex etiology and pathogenesis underlying Chronic Non-Bacterial Prostatitis (CNP), coupled with the existence of a Blood Prostate Barrier (BPB), contribute to a lack of specificity and poor penetration of most drugs. Emodin (EMO), a potential natural compound for CNP treatment, exhibits commendable anti-inflammatory, anti-oxidant, and anti-fibrosis properties but suffers from the same problems as other drugs. METHODS: By exploiting the recognition properties of lactoferrin (LF) receptors that target intestinal epithelial cells (NCM-460) and prostate epithelial cells (RWPE-1), a pathway is established for the transrectal absorption of EMO to effectively reach the prostate. Additionally, hyaluronic acid (HA) is employed, recognizing CD44 receptors which target macrophages within the inflamed prostate. This interaction facilitates the intraprostatic delivery of EMO, leading to its pronounced anti-inflammatory effects. A thermosensitive hydrogel (CS-Gel) prepared from chitosan (CS) and ß-glycerophosphate disodium salt (ß-GP) was used for rectal drug delivery with strong adhesion to achieve effective drug retention and sustained slow release. Thus, we developed a triple-targeted nanoparticle (NPs)/thermosensitive hydrogel (Gel) rectal drug delivery system. In this process, LF, with its positive charge, was utilized to load EMO through dialysis, producing LF@EMO-NPs. Subsequently, HA was employed to encapsulate EMO-loaded LF nanoparticles via electrostatic adsorption, yielding HA/LF@EMO-NPs. Finally, HA/LF@EMO-NPs lyophilized powder was added to CS-Gel (HA/LF@EMO-NPs Gel). RESULTS: Cellular assays indicated that NCM-460 and RWPE-1 cells showed high uptake of both LF@EMO-NPs and HA/LF@EMO-NPs, while Raw 264.7 cells exhibited substantial uptake of HA/LF@EMO-NPs. For LPS-induced Raw 264.7 cells, HA/LF@EMO-NPs can reduce the inflammatory responses by modulating TLR4/NF-κB signaling pathways. Tissue imaging corroborated the capacity of HA/LF-modified formulations to breach the BPB, accumulating within the gland's lumen. Animal experiments showed that rectal administration of HA/LF@EMO-NPs Gel significantly reduced inflammatory cytokine expression, oxidative stress levels and fibrosis in the CNP rats, in addition to exerting anti-inflammatory effects by inhibiting the NF-κB signaling pathway without obvious toxicity. CONCLUSION: This triple-targeted NPs/Gel rectal delivery system with slow-release anti-inflammatory, anti-oxidant, and anti-fibrosis properties shows great potential for the effective treatment of CNP.

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Chronic prostatitis (CP) is one of the diseases that reduce the quality of life (QoL) of young men. To date, there is no consensus on the management of these patients. It is essential to continue research into the treatment of CP, despite the use of various therapies, including low-energy extracorporeal shockwave therapy (ESWT). The main objective of this study is to observe and record the clinical symptomatology of patients during a 48-week follow-up period after ESWT treatment. Between 2019 and 2021, 28 patients with type IIIB CP/chronic pelvic pain syndrome were enrolled. Patients underwent ESWT once weekly for 4 weeks (3,000 individual sessions, maximum total energy flux density 0.25 mJ/mm2, frequency 3 Hz). Participants were assessed at 0, 4, 12, 24, 36 and 48 weeks post-treatment using the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and International Index of Erectile Function (IIEF)-5. The mean age of patients was 47.1 ± 13.7 years (range 28-4 years). The positive effect of LI-ESWT was reflected in improvements in VAS, NIH-CPSI, and IIEF-5 scores. Regression of patients' symptoms was observed as early as 4 weeks after treatment. The greatest progress was achieved at week 24. In addition, a slight worsening was observed at week 36 and 48, with stable progress. The treatment significantly improved the QoL of the patients, with the most significant improvement in the VAS score. In conclusion, this treatment approach is safe, most effective in the first 6 months. Thereafter, the efficacy of the treatment diminishes, but is sustained over a longer period.

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BACKGROUND: Rapeseed bee pollen has been recognized as a critical treatment for chronic non-bacterial prostatitis (CNP) and it also can modulate gut microbiota and improve gut health. This study aimed to explore the anti-prostatitis effects of rapeseed bee pollen with or without wall-disruption, and to investigate the connection between this treatment and gut microbiota. RESULTS: The results reveal that rapeseed bee pollen can effectively alleviate chronic non-bacteria prostatitis by selectively regulating gut microbiota, with higher doses and wall-disrupted pollen showing greater efficacy. Treatment with a high dose of wall-disrupted rapeseed bee pollen (WDH, 1.26 g kg-1 body weight) reduced prostate wet weight and prostate index by approximately 32% and 36%, respectively, nearly the levels observed in the control group. Wall-disrupted rapeseed bee pollen treatment also reduced significantly (p < 0.05) the expression of proinflammatory cytokines (IL-6, IL-8, IL-1ß, and TNF-α), as confirmed by immunofluorescence with laser scanning confocal microscope. Our results show that rapeseed bee pollen can inhibit pathogenic bacteria and enhance probiotics, particularly in the Firmicutes-to-Bacteroidetes (F/B) ratio and the abundance of Prevotella (genus). CONCLUSION: This is the first study to investigate the alleviation of CNP with rapeseed bee pollen through gut microbiota. These results seem to provide better understanding for the development of rapeseed bee pollen as a complementary medicine. © 2023 Society of Chemical Industry.

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Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that contributes to the production of fluid to nourish sperm and the mechanism to switch between urination and ejaculation. Prostatitis can cause frequent urination, pelvic pain, and even infertility. Long-term prostatitis increases the risk of prostate cancer and benign prostate hyperplasia. Chronic non-bacterial prostatitis presents a complex pathogenesis, which has challenged medical research. Experimental studies of prostatitis require appropriate preclinical models. This review aimed to summarize and compare preclinical models of prostatitis based on their methods, success rate, evaluation, and range of application. The objective of this study is to provide a comprehensive understanding of prostatitis and advance basic research.

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Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP. Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot. Results: In vivo, BSDZG effectively reduced the prostate index. In vivo and in vitro, BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1ß, as well as the apoptosis rate. Moreover, in vivo and in vitro, BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1ß, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro. Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1ß, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.

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Neural innervations exert essential roles in the prostate. However, spatial distribution and regulatory function of such neural inputs are incompletely characterized. Here, we exploited the advanced whole-tissue immunolabeling and optical clearing technique to assess the 3D anatomy of autonomic innervations in the mouse and human prostate for the first time. We observed that sympathetic and parasympathetic inputs in the mouse prostate remained unaffected during castration-induced tissue regression. However, the pharmacologic destruction of sympathetic innervations in the mouse prostate led to sterile inflammation of the tissue, mimicking the disease condition of chronic non-bacterial prostatitis. Also, the genetic ablation of sympathetic inputs produced a similar inflammatory response. Furthermore, we showed that treatment of the specific ß2-adrenergic receptor agonists could effectively mitigate the prostate inflammation caused by such sympathetic loss. Together, these results have elucidated the new immunomodulatory function of the sympathetic signal via the ß2-adrenergic receptor in prostate inflammatory disease.

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Mesenchymal stem cells (MSCs) own the capacity to secrete trophic factors as exosomes which play significant roles in regulating the functions of other cells and preventing inflammation. Due to the inflammatory process in chronic non-bacterial prostatitis (CNP) and the ambiguity in the treatment of this disease, the present study was aimed to investigate the therapeutic use of adipose-derived MSC exosomes in an animal model of CNP. MSCs were first isolated from rat subcutaneous adipose tissue, and exosomes were extracted from them. Specific features of exosomes were characterized by a scanning electron microscope, western blot technique, and Dynamic Light Scattering methods. To establish CNP in rats, intraprostatic injection of Freund's complete adjuvant was done. After confirmation of prostatitis, intraprostatic injections of exosomes were performed for treatment. Histological evaluation revealed that treatment with exosomes resulted in a relative improvement of lesions caused by CNP. The expression of p-NF-κB and p-IκBα proteins along with inflammatory markers was significantly increased in the CNP group, which treatment with exosomes significantly reduced their expression as well as IL-1ß and TNF-α proteins. The antioxidant effects of exosomes were also determined by significantly regulating glutathione peroxidase and superoxide dismutase activity and malondialdehyde levels in these animals. Our results cautiously suggest the therapeutic effects of MSC-derived exosomes against CNP-induced prostatitis through their antioxidant and anti-inflammatory activities, which should be further considered in the future.

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Studies have shown that the cytokine IL-6 plays an important role in the occurrence and development of chronic non-bacterial prostatitis (CNP), but the specific mechanism by which this cytokine regulates CNP is still unclear. At the same time, relevant research have also shown that autophagy is involved in regulating the occurrence and development of inflammation. The possible mechanisms are IL-6/STAT3 signaling pathway and NLRP3 inflammasome. On the basis of establishing the CNP model in rats, we found that IL-6 can regulate autophagy of CNP cells and is associated with the STAT3 pathway and NLRP3 inflammasome. Our results indicate that IL-6 is involved in the regulation of autophagy signaling pathways in CNP. IL-6/STAT3 signaling pathway can suppress cell autophagy pathway in CNP; And the NLRP3 inflammasome may regulate CNP cell autophagy by regulating the IL-6/STAT3 pathway. These findings may provide a new theoretical basis for the pathogenesis of CNP, as well as new ideas and new targets for the treatment and prevention of CNP.

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Qianliexin capsule (QLX) is a standardized traditional Chinese herbal preparation that has long been used to treat chronic non-bacterial prostatitis (CNP) and benign prostatic hyperplasia (BPH). This study investigated the anti-inflammatory activity of QLX in improving lower urinary tract symptoms (LUTS) associated with CNP and BPH. Rat models of CNP and BPH were induced by oestradiol or testosterone (hormonal imbalance) or chemical inflammation (carrageenan). QLX significantly relieved LUTS in CNP and BPH rat model by reducing prostate enlargement, epithelial thickness, pain response time, urine volume and bleeding time, and by improving prostatic blood flow. The expression of the pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, the pro-inflammatory transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and inflammasome components (NLRP3, caspase-1 and ASC) in CNP and BPH tissues was reduced by QLX addition. QLX treatment was followed by reduced cellular malondialdehyde and increased superoxide dismutase, catalase and glutathione peroxidase activity, consistent with antioxidant activity. Increases in Beclin-1 expression and the LC3II/I ratio following QLX treatment indicated that autophagy had been induced. QLX relieved LUTS in CNP and BPH rat models by inhibiting inflammation. The underlying mechanisms included inhibition of inflammasome activation, NF-κB activation, oxidant stress and autophagy.

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Chronic non-bacterial prostatitis (CNP) is one of the most prevalent diseases in human males worldwide. In 2005, the prostate-gut axis was first proposed to indicate the close relationship between the prostate and the intestine. This study investigated CNP-induced changes of the gut microbiota, gene expression and DNA methylation in a rat model by using multi-omics analysis. Firstly, 16S rDNA sequencing presented an altered structure of the microbiota in cecum of CNP rats. Then, transcriptomic analysis revealed that the expression of 185 genes in intestinal epithelium was significantly changed by CNP. These changes can participate in the immune system, digestive system, metabolic process, etc. Finally, methylC-capture sequencing (MCC-Seq) found 73,232 differentially methylated sites (DMSs) in the DNA of intestinal epithelium between control and CNP rats. A combined analysis of methylomics and transcriptomics suggested an epigenetic mechanism for CNP-induced differential expression genes correlated with intestinal barrier function, immunity, metabolism, enteric infectious disease, etc. More importantly, the transcriptomic, methylomic and gut microbial changes were highly correlated with multiple processes including intestinal immunity, metabolism and epithelial barrier function. In this study, disrupted homeostasis in the gut microbiota, gene expression and DNA methylation were reported in CNP, which supports the existence of the gut-prostate axis.

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BACKGROUND: Prostatitis is the most commonly diagnosed disease in men younger than 50 years and accounts for about 8% of all urologists' consultations. OBJECTIVE: After evaluating clinical trials and demonstrating the efficacy of chronic non-bacterial prostatitis treatment, it remains of clinical importance to continue studies on the use of low-energy extracorporeal shock wave therapy (ESWT) in men. MATERIALS AND METHODS: From May 2017 to April 2018, 40 patients with chronic prostatitis (CP) type IIIB/chronic pelvic pain syndrome (CPPS) were enrolled in the study. The patients underwent ESWT once a week for 4 weeks. RESULTS: The mean age of the patients was 47.8 years. A statistically significant improvement in all the parameters, i.e., the International Prostate Symptom Score (IPSS), the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and the International Index of Erectile Function (IIEF), was observed at week 4. The effect of the treatment was maintained during the entire 12-week period. The NIH-CPSI total score showed the best improvement at week 4, but a slight deterioration without a statistically significant change was noticed at week 12. The greatest improvement at week 4 was documented for the NIH-CPSI and IPSS (43% and 37%, respectively). At week 12, an improvement of 52% and 39% was recorded for VAS and IPSS, respectively. CONCLUSIONS: Our findings confirmed the effectiveness and safety of ESWT in resistant cases of CPPS in the short term. ESWT is cost-effective, which takes little time or requires a small amount of staff, and is easily conducted.

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INTRODUCTION: The etiology of abacterial CP/CPPS (category III) has not been studied enough. Currently, there is no gold standard of diagnostic study and optimal treatment algorithm. AIM: The aim of our study was to study three human herpes viruses (HHV) in clinical samples from patients with inflammatory diseases of urogenital tract and to evaluate the efficiency of proposed treatment algorithm for abacterial CP/CPPS. MATERIALS AND METHODS: The biological samples from the urogenital tract (urethral swab, ejaculate and expressed prostatic secretions) from 101 patients with category III CP/CPPS were studied. Quantitative analysis of HHV DNA (CMV, EBV and HHV-6) was performed by PCR. RESULTS: HHV DNA was detected in 38/101 patients (37.6%) in Group 1. Among the detected viral types, HHV-6 was the most common (52%). Analysis of biological samples form the three sources revealed that viral DNA was determined in urethral swab in concentration of 3,703,900 copies/ml. In Group 2, viral DNA was not detected in 63 patients. Evaluation of results of the standard treatment in HHV-negative patients (n=63) and antibiotic-free scheme, including the immunoregulatory drug Viferon, in HHV-positive patients (n=38) showed that the number of HHV-positive samples after treatment decreased by 54.3%. In addition, severity of all symptoms according to NIH-CPSI scale significantly decreased in both groups (p<0.0001). There was an improvement in all clinical symptoms in Group 1 by 47.9%, especially for pain + urination (52%). It should be noted that a positive response to treatment, which was confirmed by the changes in total score of NIH-CPSI scale, was noted in all patients in Group 1. CONCLUSION: Detection of herpes viruses in the urogenital tract of patients with abacterial CP/CPPS suggests possible role of viral infections in its etiology. The comparative analysis of the results of standard treatment including antiviral, immunomodulatory and antioxidant drugs showed that the use of complex therapy without antibiotics allowed to eliminate or significantly reduce the concentration of viruses in urogenital tract, as well as significantly reduce the clinical manifestations of abacterial CP/CPPS.

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Chronic non-bacterial prostatitis (CNP) is a common urologic disease that is linked to the development of prostate cancer. Long non-coding RNA (lncRNA) GAS5 has been identified to mediate cell proliferation in prostate cancer, although its role in CNP is still unclear. Human prostate epithelial cell line RWPE-1 was induced by lipopolysaccharide (LPS) to mimic CNP model in vitro. Real-time PCR was performed to determine the expression of GAS5 and COX-2, while western blotting was used to evaluate the protein expression of COX-2. The interaction between GAS5 and COX-2 was determined using RNA pull-down and RNA immunoprecipitation (RIP). Cell proliferation was determined using MTT assay. The expression of GAS5 was decreased, while COX-2 was increased in prostatitis tissues and in LPS-induced RWPE-1 cells. The overexpression of GAS5 suppressed the protein level of COX-2, and inhibited cell proliferation of LPS-induced RWPE-1 cells and HPECs, which was rescued by the co-transfection with pcDNA-GAS5 and pcDNA-COX-2. GAS5 was confirmed to promote the ubiquitination of COX-2, and the in vivo GAS5-overexpressed CNP rat model decreased the motor scores, the volume of prostate tissues, the average number of inflammatory cells, prostatic proliferation, and COX-2 expression. Our findings revealed that overexpression of GAS5 inhibited cell proliferation via negatively regulating the expression of COX-2, thus alleviating the progression of CNP.

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BACKGROUND: A significant number of men who are younger than 50 years visit urologists for interminable prostatitis. This study aimed to thoroughly investigate the effect of pumpkin seed oil (PSO) phonophoresis on chronic nonbacterial prostatitis (CNBP). SUBJECTS AND METHODS: Sixty patients with CNBP were randomly assigned to three groups: Group A, wherein patients were treated with PSO using phonophoresis; Group B, where patients underwent transperineal continuous low-intensity ultrasound (LIUS); and Group C, wherein patients underwent placebo LIUS. All three groups received their corresponding treatments daily for up to 3 weeks. The NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), residual urine determined by urodynamic measurements, and flow rate were used to analyze study outcomes. The white blood cell (WBC) count in the prostatic secretion was determined. RESULTS: Comparisons of the intragroup mean values of all measurements in Groups A and B before and after the end of the treatment showed a significant improvement in residual urine, flow rate, WBC count, and NIH-CPSI (p < 0.05), whereas no significant change was found in Group C (p > 0.05). Between-group comparisons of all variables showed a significant difference was found after intervention (p < 0.05). Postintervention comparisons between Groups A and B showed a significant difference in all measurements, except for WBC, in favor of Group A. Comparing the changes between Groups A and C, a significant difference was found in all measurements (p < 0.05). Furthermore, all parameters differed significantly when comparing Groups B and C (p < 0.05). CONCLUSION: The current study showed that PSO phonophoresis can produce a significant effect in the management of CNBP and can, therefore, be considered a safe, noninvasive method for the treatment of CNBP.

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OBJECTIVE:To investigate the improvement effect of Prostatitis capsule on chronic non-bacterial prostatitis(CNP) model rats. METHODS:60 rats were randomly divided into sham operation group (distilled water),model group (distilled wa-ter),Pule'an tablet group(positive control,2 g/kg)and Prostatitis capsule high-dose,medium-dose,low-dose groups(16,8,4 g/kg). Except for sham operation group,other 5 groups were injected Xiaozhiling injection 0.2 mL to reduce CNP model. After 7 d of modeling,they received related medicines,ig,once a day,for 45 d. After 24 h of last administration,prostate lesions were ob-served by eyes and wet quality was weighed. White blood cell(WBC)count and lecithin body(SPL)count were conducted under microscope,and prostate tissue slices were pathologically observed. RESULTS:Compared with sham operation group,prostate showed gray nodules,adhesion in glands and surrounding tissue;wet quality of prostate and WBC,SPL count in prostate tissue were significantly increased(P<0.01);under microscope,there were significant congestion,edema and a variety of inflammatory cell infiltration in prostate interstitial. Compared with model group,gray nodules in prostate in Pule'an tablet group and Prostatitis capsule group were reduced,as well as adhesion degree in prostate and surrounding tissue;wet quality of prostate and WBC,SPL count in prostate tissue were significantly decreased(P<0.01);pathological changes had improved to varying degrees under micro-scope,especially the changes in Prostatitis capsule high-dose group,and prostate tissue only showed mild congestion,edema and little inflammatory cell infiltration. CONCLUSIONS:Prostatitis capsule has a certain improvement effect on CNP model rats.

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Objective:To explore the effect of the methanol extract of Macrothelypteris oligophlebia on chronic non-bacterial prosta-titis ( CNP) in rats to confirm the active fractions. Methods:The powdered rhizomes of M. oligophlebia were soaked in methanol. The methanol extract was suspended in water and then extracted successively with chloroform and ethyl acetate to obtain chloroform fraction, ethyl acetate fraction and water fraction. Carrageenan-induced CNP in rats was established. The rats were randomly divided into the sham-operated control group, model group, positive control group, methanol extract group, ethyl acetate fraction group, chloroform fraction group and water fraction group. The anti-prostatitis effect was evaluated by the prostate index, and the pathological examination of prostate was performed using HE staining. The levels of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-α), cyclooxyge-nase-2 (COX-2) and prostaglandin E2(PGE2) were analyzed using ELISA kits. Results:The ethyl acetate fraction group and metha-nol extract group with high flavonoid content could significantly decrease prostate index (P<0. 01) and the levels of IL-10, TNF-α, COX-2 and PGE2(P<0. 05 or P<0. 01), and improve the prostate morphology when compared with the model group, especially with the ethyl acetate fraction group. Conclusion:The rhizomes of M. oligophlebia show promising therapeutic effect on CNP, and the ethyl acetate fraction is the active fraction.

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Objective To study the action of Mycoplasma genitulium (Mg) in pathogenesis of chronic non-bacterial prostatitis. Methods Mg culture and polymerase chain reaction (PCR) were perfomed on prostatic secretion specimens from 987 patients with chronic non-bacterial pristatitis and 125 healthy men. Results ①The positive rate of Mg in the prostatic secretion from the 987 patients was 31.5% (302/987). Among the 302 positive cases, 153 cases had other pathogens, of which Ureaplasma urealyticum (Uu) was the most (128). ②In the controls, the positive rate of Mg was 2. 53% (3/125). The difference between the two groups was statistically significant (X2=44. 32,P