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Interstitial cystitis (IC) is a chronic bladder inflammation. Inhibition of prostaglandin G/H synthase 2 (PTGS2) is the most common method for controlling inflammation-related diseases. This study aimed to analyze the effects of hispidulin on the PTGS2 and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammation in experimental IC models. A binding activity between hispidulin and PTGS2 was measured using molecular docking. Human urothelial cells (SV-HUC-1) were stimulated by 2 ng/mL of interleukin (IL)-1β for 24 h and cultured in a medium with different concentrations of hispidulin (2.5, 5, 10, 20 µM) for 24 h to observe the expressions of PTGS2 and NLRP3 protein. Cells overexpressing PTGS2 were established by PTGS2 cDNA transfection. In the IL-1β-treated cells, the NLRP3 inflammasome was measured after 20 µM hispidulin treatment. In rats, animals were performed with three injections of 40 mg/kg cyclophosphamide (CYP) and orally treated with 50 mg/kg/day hispidulin or ibuprofen for 3 days. The bladder pain was measured using Von Frey filaments, and the bladder pathology was observed using hematoxylin and eosin (H&E) staining. The expressions of PTGS2 and NLRP3 inflammasome were also observed in the bladder tissues. A good binding activity was found between hispidulin and PTGS2 (score =  − 8.9 kcal/mol). The levels of PTGS2 and NLRP3 inflammasome were decreased with the hispidulin dose increase in the IL-1β-treated cells ( p  < 0.05). Cells overexpressing PTGS2 weakened the protective effects of hispidulin in the IL-1β-treated cells ( p  < 0.01). In the CYP-treated rats, hispidulin treatment improved the bladder pain through decreasing the nociceptive score ( p  < 0.01) and suppressed the bladder inflammation through suppressing the expressions of PTGS2 and NLRP3 inflammasome in bladder tissues ( p  < 0.01). Additionally, the results of ibuprofen treatment were similar to the effects of hispidulin in the CYP-treated rats. This study demonstrates that hispidulin may be a new alternative drug for the IC treatment that binds PTGS2 to perform its functions.

The optimal management of hemorrhagic cystitis (HC) in hematopoietic stem cell transplantation (HCT) is debated, both for early onset HC (EOHC) secondary to chemotherapy toxicity and BK Polyomavirus (BKPyV)-related HC, due to the lack of controlled trials, particularly referred to pediatric setting. Actually, clinical practice is mainly based on guidelines of the European Conference on Infections in Leukemia, 6th edition, which considers both adult and pediatric populations but concludes that, despite much progress in understanding the pathogenesis, epidemiology, and risk factors, this complication still represents a disabling unmet clinical need with limited prophylactic and therapeutic options. Additionally, the Guidelines of the American Society of Clinical Oncology define the management of chemotherapeutic toxicity independently from the patients’ population. A panel of experts belonging to the Hematopoietic Cell Transplant and Infectious Disease Working Group (WG) of Associazione Italiana di Emato-Oncologia Pediatrica (AIEOP) developed a consensus to define the best practices in prevention, diagnosis, and management of HC in pediatric HCT setting.

This study aimed to elucidate distinct cellular and immunological characteristics associated with chronic inflammatory conditions of the urinary bladder, including Hunner-type interstitial cystitis (HIC), bacillus Calmette–Guérin (BCG)-related cystitis, follicular cystitis (FC), and chronic bacterial cystitis (CBC). Transcriptomic analyses using next-generation RNA sequencing, along with quantitative polymerase chain reaction, were performed on mucosal bladder biopsies to assess the whole transcriptional and immune-response profiles. Furthermore, digital immunohistochemical quantification evaluated urothelial denudation and the densities of infiltrating immune cells, including T-lymphocytes, B-lymphocytes, mast cells, and plasma cells. HIC specimens exhibited a markedly distinct transcriptional profile, with 3,566 differentially expressed genes and enrichment of 116 biological processes particularly associated with microbial response and heightened autoimmunity with Th1/Th17 axis polarization. Histologically, HIC bladders demonstrated significant epithelial denudation, elevated IL-17-positive cell density, and increased plasma cell ratios compared to other cystitis types. No significant differences were observed in overall lymphoplasmacytic or mast cell densities, nor in B cell ratios among the groups. These findings underscore a unique immunopathological signature in HIC, characterized by plasma cell predominance within a Th1/17-polarized immune environment and epithelial denudation, offering new insights into its pathogenesis and therapeutic targeting.

PurposeInterstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain syndrome and a chronic inflammatory condition prevalent in women that leads to urgency, sleep disruption, nocturia and pain in the pelvic area, to the detriment of the sufferer’s quality of life. The aim of this review is to highlight the newest diagnostic strategies and potential therapeutic techniques.MethodsA comprehensive literature review was performed on MEDLINE, PubMed, and Cochrane databases gathering all literature about “Interstitial cystitis” and “Painful Bladder Syndrome”. Visual analogue scales, epidemiological strategies, pain questionnaires and similar techniques were not included in this literature survey.ResultsThe etiology, exact diagnosis and epidemiology of IC/PBS are still not clearly understood. To date, its prevalence is estimated to be in the range of 45 per 100,000 women and 8 per 100,000 men, whereas joint prevalence in both sexes is 10.6 cases per 100,000. There are no “gold standards” in the diagnosis or detection of IC/PBS, therefore, several etiological theories were investigated, such as permeability, glycosaminoglycans, mast cell, infection and neuroendocrine theory to find new diagnostic strategies and potential biomarkers.ConclusionDue to the fact that this disease is of an intricate nature, and that many of its symptoms overlap with other concomitant diseases, it could be suggested to classify the patients with emphasis on the phenotype, as well as their symptom clusters, to tailor the diagnostic and management choices according to the observed biomarkers.

This study explored the impact of transurethral resection plus sapylin for bladder perfusion in treating glandular cystitis. One hundred and twenty-eight cases of glandular cystitis who accepted therapy in Renmin Hospital of Wuhan University, Wuhan, China from September 2018 to September 2022 were chosen and randomly separated into a control group (CG, n=64) and a research group (RG, n=64). The CG received transurethral resection. In contrast, the RG received sapylin infusion chemotherapy in addition to transurethral resection. The clinical efficacy, urination function, levels of inflammatory factors, quality of life along with adverse reactions in the two groups was compared. Relative to the CG, the RG showed higher total treatment effectiveness rate, better improvements of urination function and inflammation, higher quality of life scores, and lower occurrence of adverse reactions. We conclude that transurethral resection combined with sapylin for bladder perfusion has higher effectiveness in treatment of glandular cystitis when compared to transurethral resection alone. Cette étude a exploré l'impact de la résection transurétrale associée à la sapyline pour la perfusion vésicale dans le traitement de la cystite glandulaire. Cent vingt-huit cas de cystite glandulaire, traités à l'hôpital Renmin de l'université de Wuhan, en Chine, entre septembre 2018 et septembre 2022, ont été sélectionnés et répartis aléatoirement en un groupe témoin (GC, n = 64) et un groupe de recherche (RG, n = 64). Le GC a bénéficié d'une résection transurétrale. À l'inverse, le RG a reçu une chimiothérapie par perfusion de sapyline en plus de la résection transurétrale. L'efficacité clinique, la fonction urinaire, les niveaux de facteurs inflammatoires, la qualité de vie et les effets indésirables des deux groupes ont été comparés. Par rapport au GC, le RG a montré un taux d'efficacité thérapeutique global plus élevé, une meilleure amélioration de la fonction urinaire et de l'inflammation, des scores de qualité de vie plus élevés et une incidence plus faible d'effets indésirables. Nous concluons que la résection transurétrale associée à la sapyline pour la perfusion vésicale est plus efficace dans le traitement de la cystite glandulaire que la résection transurétrale seule.

Background Urinary tract infections are common affections, especially for women. Difficult access to a general practitioner to obtain a prescription has led France to offer dispensing under protocol by community pharmacists. The primary objective of this study is to evaluate the effectiveness of a pharmacist care protocol provided to manage women with urinary tract infection symptoms. This objective will be assessed using the Acute Cystitis Symptom Score. Methods PharmaCyst’ is an open-label, multicenter, controlled, cluster-randomized study conducted in the Loire region, France. Women aged between 18 and 65 years presenting to a pharmacy complaining of at least one symptom of an uncomplicated urinary tract infection present over the last 3 days (including burning pain during micturition, dysuria, pollakiuria, urgent urination) will be considered for inclusion. All patients will be contacted on day 3, 10, and month 3. A total of 480 patients need to be recruited for the 24 clusters participating in the research. The quantitative data will be described using means and standard deviations and compared using Student’s t -test. The qualitative data will be described using numbers and percentages and compared using chi 2 test (or Fisher’s exact test if necessary). The primary and secondary outcomes analyses will consider the intention-to-treat population. Discussion PharmaCyst’ is the first clinical trial conducted in France only by community pharmacists. Its results could lead to an extension of the protocol. Trial registration The protocol has been approved by the French ethics committee on 2022/12/02 and is registered under the number 49RC22_0240 on ClinicalTrials.gov.

Introduction and hypothesisPatients with interstitial cystitis/bladder pain syndrome (IC/BPS) often experience chronic pelvic and even systemic pain that can be difficult to clinically manage.Pulsed electromagnetic field (PEMF) therapy, a non-invasive strategy that has shown significant efficacy for pain reduction in other chronic pain conditions, may provide benefit for pain management in patients with IC/BPS.MethodsPEMF delivery to patients occurs via a bio-electromagnetic-energy device which consists of a flexible mat (180 × 50 cm) that the patient lies on for systemic, full-body delivery and/or a flexible pad (50 × 15 cm) for targeted delivery to a specific body region (e.g., pelvic area). The duration of individual sessions, number of sessions per day, total number of sessions, and follow-up observation period vary between previously published studies. Positive outcomes are typically reported as a significant reduction in visual analog scale (VAS) pain score and functional improvement assessed using validated questionnaires specific to the condition under study.Results and conclusionsThe use of PEMF has been evaluated as a therapeutic strategy for pain management in several clinical scenarios. Randomized, double-blinded, placebo-controlled trials have reported positive efficacy and safety profiles when PEMF was used to treat non-specific low back pain, patellofemoral pain syndrome, chronic post-operative pain, osteoarthritis-related pain, rheumatoid arthritis-related pain, and fibromyalgia-related pain. Based on these positive outcomes in a variety of pain conditions, clinical trials to evaluate whether PEMF can provide a safe, non-invasive therapeutic approach to improve symptoms of chronic pain and fatigue in patients with IC/BPS are warranted.

The pathogenesis of bladder pain syndrome/interstitial cystitis (BPS/IC) is currently unclear. However, inflammation has been suggested to play an important role in BPS/IC. JNK downstream signaling plays an important role in numerous chronic inflammatory diseases. However, studies of the JNK pathway in BPS/IC are limited. In this study, we investigated the role of the JNK pathway in human BPS/IC and rat protamine sulfate (PS)-induced cystitis and examined the effect of the selective JNK inhibitor SP600125 on rat bladder cystitis. In our study, we demonstrated that the JNK signaling pathway was activated (the expression of JNK, c-Jun, p-JNK, p-c-Jun, IL-6 and TNF-α were significantly increasing in BPS/IC compared to the non-BPS/IC patients) and resulted in inflammation in human BPS/IC. Further animal models showed that the JNK pathway played an important role in the pathogenesis of cystitis. JNK inhibitors, SP600125, effectively inhibited the expression of p-JNK, p-c-Jun, IL-6 and TNF-α. The inhibition of these pathways had a protective effect on PS-induced rat cystitis by significantly decreasing histological score and mast cell count and improving bladder micturition function (micturition frequency significantly decreasing and bladder capacity significantly increasing). Therefore, JNK inhibition could be used as a potential treatment for BPS/IC.

Interstitial cystitis/bladder pain syndrome (IC/BPS) plagues patients and clinicians with its unclear etiology and pathogenesis, and ineffective treatments. Destruction of epithelial tissue and proliferation of interstitial tissue are typical pathological features of IC/BPS, in which epithelial-mesenchymal transition (EMT) may play an important role. Both the increased urination frequency observed in mice with acute cystitis induced by cyclophosphamide (CYP) and the disruption of the anti-leakage barrier in urothelial cells induced by LPS are associated with the occurrence of EMT. The expression of heparanase 1 (HPSE) and syndecan-2 (SDC-2) is up-regulated in the bladder mucosa of patients with IC, and both of them can promote the development of EMT. Improvement of lower urinary tract symptoms and restoration of the uroepithelial cell anti-leakage barrier in mice with CYP-induced cystitis after treatment with the HPSE inhibitor OGT2115 and inhibited the development of EMT. We then verified that HPSE binds to SDC-2 and that SDC-2 is a key intermediate protein in the pro-EMT role of HPSE, and that EMT was inhibited by knockdown of SDC-2. SDC-2 exerts its biological function by inhibiting the ubiquitinated degradation of TGF-βR1. Here we identified a novel mechanism by which the HPSE/ SDC-2 axis promotes EMT development and thus causes epithelial dysfunction and altered voiding behavior, providing a new direction for the treatment of IC/BPS.

Although interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing bladder pain and urinary symptoms, effective treatments have not been established. The aim of this study was to adapt a chronic cystitis model in rats using lipopolysaccharide (LPS), which reflects IC/BPS pathology, and characterize the model's histological and behavioral effects. Furthermore, we investigated the effect of an α2δ subunit ligand, gabapentin (GBP), on bladder hypersensitivity of rats with chronic cystitis. Cystitis models were created by repeated intravesical injections of LPS. In the histological examination, the LPS‐injected group had greater inflammatory response, fibrosis, and abnormally thick re‐epithelialization. In the LPS‐injected group, LPS prompted hyperalgesia in both the lower abdomen and hind paw regions after day 1 of the first injection compared with the saline‐injected controls, without any recovery for 21 days at least. During cystometry, the LPS‐injected group showed bladder hyperactivity at all times. Systemic administration of GBP reduced cystitis‐related pain due to chronic inflammation and reduced the increased frequency of voiding in the LPS‐injected group. These results suggest that repeated intravesical injections of LPS induce long‐lasting bladder inflammation, pain, and overactivity in rats, while GBP is effective in the management of those symptoms in this chronic cystitis model. The current study identifies a relatively simple method to develop an animal model for chronic cystitis and provides evidence that GBP may be an effective treatment option for patients with IC/BPS. This study shows the repeated intravesical injections of lipopolysaccharide (LPS) could be used to generate a model of chronic cystitis in rats, which show signs of long‐lasting bladder inflammation, pain, and overactivity. Gabapentin, a neuromodulator, effectively inhibited bladder pain and overactivity in the LPS‐induced chronic cystitis rats.