Bladder Mucosa Research Articles

Mimicking Urinary Tract Infections Caused by Uropathogenic Escherichia coli Using a Human Three-Dimensional Tissue Engineering Model

Uropathogenic Escherichia coli are the main causal agent of urinary tract infections. These diseases can affect more than half of women during their lifetime. Moreover, recurrent urinary tract infections can affect up to 30% of patients, leading to higher social and economic costs for the community. No efficient treatment against the recurrent form of the disease has been discovered. Due to the low average rate of successful translation from 2D cell culture and in vivo animal models into clinical trials, new models that mimic pathologies, such as those produced by tissue engineering, are needed. A model of human-derived 3D bladder mucosa was produced by tissue engineering techniques using collagen gels and organ-specific primary human stromal and epithelial cell populations. This model was used to mimic the different steps of a urinary tract infection: adhesion, invasion, intracellular bacterial community and quiescent intracellular reservoir formation and, finally, bacteria resurgence after umbrella cell exfoliation through chitosan exposure to mimic the recurrent infection. The uropathogenic strain UTI-89-GFP was used as infectious bacteria and BL-21-GFP strain as a control. Our model is unique and is the first step toward mimicking the different phases of a UTI in a human context.

PERITONEAL KERATIN GRANULOMAS MIMICKING PERITONEAL CARCINOMATOSIS: A POTENTIAL DIAGNOSTIC PITFALL

Abstract Introduction/Objective Keratin granulomas from a primary uterine cancer can present as peritoneal tumor nodules, mimicking peritoneal carcinomatosis. Endometrial adenocarcinomas with viable peritoneal tumor implants and/or involvement of bladder or bowel mucosa are categorized as stage IV disease. We present a rare case of endometrial adenocarcinoma of the uterus with squamous differentiation and multiple peritoneal nodules of keratin granulomas, masquerading as peritoneal carcinomatosis. Methods/Case Report A 68-year-old female with insignificant past medical history presented with complaints of postmenopausal bleeding for the past four months. Physical examination was unremarkable. Transvaginal ultrasound showed a 4.9 cm echogenic mass in the uterus. The endometrial biopsy showed squamous debris with atypical cells suspicious of malignancy. Endometrial curettings revealed endometrial adenocarcinoma, endometrioid type with squamous differentiation, FIGO Grade 1. Subsequently, she underwent hysterectomy with bilateral salpingo- oophorectomy. Intraoperatively, multiple suspicious nodules on the sigmoid colon and in the pelvis were identified, of which excisional biopsies and pelvic peritoneal washing were taken. Microscopic examination of the resection confirmed endometrial adenocarcinoma, FIGO Grade 1, nuclear grade 1, with extensive foreign body giant cell reaction to dead squamous cells (ghost cells). Cytologic examination of the peritoneal washing was unremarkable and excisions of the sigmoid serosal and peritoneal nodules showed pink eosinophilic laminated nodules surrounded by inflammatory cells including plasma cells, lymphocytes and multinucleated giant cells without any viable tumor cells. Results (if a Case Study enter NA) NA Conclusion Keratin granulomas are a foreign body reaction to keratin deposition from the squamous component of endometrioid adenocarcinoma. The pathogenesis of this foreign body response to keratin is considered to be a trans- tubal spread of keratin through retrograde shedding from the fallopian tubes. In the absence of viable tumor cells, it appears to have no negative prognostic significance. Careful microscopic examination of peritoneal keratin granulomas is imperative to avoid erroneous upstaging of the tumor and the subsequent advanced treatment.

31 - Enhanced brain-derived neurotrophic factor and reactive oxygen species in the mucosa of lower motor neuron-lesioned dog bladder following somatic-motor nerve transfer

31 - Enhanced brain-derived neurotrophic factor and reactive oxygen species in the mucosa of lower motor neuron-lesioned dog bladder following somatic-motor nerve transfer

New compact micro-hole zone catheter enables women to achieve effective bladder emptying without flow-stops.

Clean intermittent self-catheterisation (CISC) with conventional eyelet catheters (CECs) is associated with urine flow-stops, which require the catheter to be repositioned so flow can resume. Flow-stops often occur because bladder mucosa is sucked into the eyelets. This investigation aimed to compare the bladder-emptying performance of the micro-hole zone catheter (MHZC) with the CEC. This was a multi-centre, randomised, open-label, controlled cross-over study with 82 women comparing the MHZC to the CEC. The endpoints relating to bladder-emptying performance included the residual volume at first flow-stop, the number of flow-stops and the proportion of successful treatment responses. The women's perception of the catheters was assessed as well as device discomfort. Catheterisations with MHZC significantly reduced the risk of flow-stops, with relative risk results showing a 2.74 times lower risk of flow-stops with a health professional-led catheterisation and a 2.52 times lower risk during self-catheterisation. There was no statistical difference in residual urine volume at first flow-stop between the two catheters. Catheterisations with the MHZC were significantly more likely to achieve zero flow-stops and a residual urine volume of <10 ml at first flow-stop. The women had a significantly more positive perception of the MHZC than the CEC in areas including handling, confidence, sensation and satisfaction. The MHZC enabled effective bladder emptying without catheters needing to be repositioned, supporting the women by simplifying the procedure and making them feel confident that their bladders were empty.

Activation of Piezo1 channels enhances spontaneous contractions of isolated human bladder strips via acetylcholine release from the mucosa

Enhanced spontaneous bladder contractions (SBCs) have been thought one of the important underlying mechanisms for detrusor overactivity (DO). Piezo1 channel has been demonstrated involved in bladder function and dysfunction in rodents. We aimed to investigate the modulating role of Piezo1 in SBCs activity of human bladder. Human bladder tissues were obtained from 24 organ donors. SBCs of isolated bladder strips were recorded in organ bath. Piezo1 expression was examined with reverse transcription-quantitative polymerase chain reaction and immunofluorescence staining. ATP and acetylcholine release in cultured human urothelial cells was measured. Piezo1 is abundantly expressed in the bladder mucosa. Activation of Piezo1 with its specific agonist Yoda1 (100 nM–100 μM) enhanced the SBCs activity in isolated human bladder strips in a concentration-dependent manner. The effect of Yoda1 mimicked the effect of a low concentration (30 nM) of carbachol, which can be attenuated by removing the mucosa, blocking muscarinic receptors with atropine (1 μM), and blocking purinergic receptors with pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate (PPADS, 30 μM), but not by tetrodotoxin (1 μM). Activation of urothelial Piezo1 with Yoda1 (30 μM) or hypotonic solution induced the release of ATP and acetylcholine in cultured human urothelial cells. In patients with benign prostatic hyperplasia, greater Piezo1 expression was observed in bladder mucosa from patients with DO than patients without DO. We conclude that upregulation and activation of Piezo1 may contribute to DO generation in patients with bladder outlet obstruction by promoting the urothelial release of ATP and acetylcholine. Inhibition of Piezo1 may be a novel therapeutic approach in the treatment of overactive bladder.

Evaluation of transurethral GreenLight laser-selective vaporization for refractory overactive bladder in women.

Refractory overactive bladder (OAB) in women is a common yet challenging condition for which traditional treatments have been unsatisfactory. This study aimed to evaluate the efficacy and safety of transurethral bladder mucosal GreenLight laser-selective vaporization for treating refractory OAB in women. The female patients with refractory OAB who were admitted to the Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University between May 2022 and July 2023 were examined retrospectively in this study. Transurethral bladder mucosal GreenLight laser-selective vaporization was used to treat the patients, and the perioperative and postoperative parameters were reviewed and compared. Bladder mucosa was examined by immunohistochemical staining to explore the expressions of TRPV1, P2X3, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) before and after treatments. Surgeries were performed successfully for all 32 patients in 57.38±11.22 minutes with minimal intraoperative bleeding. Twelve weeks post-surgery, there was a significant decrease (P<0.05) in the patients' Overactive Bladder Symptom Score (OABSS), 3-day bladder diary (daytime frequency, nocturia, urgency, and urgency incontinence), and Overactive Bladder questionnaire Short Form (OAB-qSF) score. After treatments, both first desire to void (FDV) and maximum bladder pressure capacity (MCBC) increased significantly (P<0.05). The immunohistochemical analysis revealed that the GreenLight laser significantly reduced the expressions of TRPV1, P2X3, TNF-α, and IL-6 in the bladder mucosa (P<0.05). No severe complications were observed after interventions. For female patients with refractory OAB who have shown poor response to conventional treatment approaches, transurethral bladder mucosal GreenLight laser-selective vaporization may represent a promising alternative treatment option.

"Five-Step" Vaporization of the Prostate Using 180-W XPS Greenlight Laser in Patients with Benign Prostatic Hyperplasia of Large Volume: Improved Efficacy and Safety.

Objective: To evaluate the safety and efficacy of 180-W XPS Greenlight laser "Five-step" photoselective vaporization of the prostate (PVP) in patients with benign prostatic hyperplasia (BPH) with prostate volume (PV) > 80 mL. Background: In patients with BPH with large PV, PVP often results in bleeding, unclear visual field, additional damage, and insufficient tissue vaporization. Methods: This single-center, retrospective study enrolled patients with BPH with PV > 80 mL treated with the Five-step PVP or the Conventional PVP from January 2018 to June 2021. Comorbidities, high-risk habits, and operative parameters were analyzed and compared. The short-term functional outcomes and postoperative complications were recorded over the 24-month follow-up. Results: Two hundred eligible patients were divided into the Five-step PVP and Conventional PVP groups (n = 100 each). These groups showed no differences in comorbidities, living habits, baseline perioperative parameters, operative time, lasing time, or energy use. However, a higher energy density (3.95 [interquartile range (IQR) 3.37, 4.52] vs 3.68 [IQR 3.17, 4.20] kJ/mL) and energy-time ratio (7.23 [IQR 6.12, 8.52] vs 6.72 [IQR 5.51, 7.87] kj/min p = 0.034)were obtained in the Five-step PVP group. Subgroup analysis of patients with PV ≥120 mL showed similar results. The short-term functional outcomes were similar between the two study groups with significant improvement from baseline, but the total prostate-specific antigen levels at 1 and 6 months were lower in the Five-step PVP group. Further, incidences of intraoperative bleeding, bladder mucosa injury, postoperative hematuria, and urinary tract infection were lower in the Five-step PVP group. In the Conventional PVP group, four patients required conversion to transurethral resection of the prostate in surgery and two patients required retreatment during the 24-month follow-up. Conclusions: The 180-W XPS Greenlight laser Five-step PVP has advantages of less bleeding, high vaporization efficiency, and low rates of perioperative complications, and, therefore, it is a promising treatment to improve short-term functional outcomes for patients with BPH with large PV.

Comparative evaluation of bioavailability of Botulinum toxin A complexed with Tizol (titanium glycerosolvate aquacomplex) versus pure Botulinum toxin A solution for bladder mucosa: an experimental study

Introduction. For the treatment of overactive bladder syndrome (OAB), injection of botulinum toxin A (BoNT-A) has been shown to be effective. However, there is a need for a less invasive method for administering BoNT-A, which could significantly expand the treatment options for OAB.Objective. To assess the impact of tizol on the absorption of BoNT-A by the bladder mucosa and compare it to the individual absorption of BoNT-A.Materials &amp; Methods. Dialysis through the mucous membrane of the сalf bladder was used as an experimental model to study changes in bioavailability of BoNT-A complexed with tisol (BoNT-A + T) and pure BoNT-A solution during in vitro experiment. After dialysis, the BoNT-A concentration in both samples was determined using a spectrophotometer. Dialysis curves were plotted according to the data obtained. Kruvchinsky equilibrium dialysis method was used to determine botulinum toxin A bioavailability. The UV spectrophotometry method was used to determine the concentration of BoNT-A in the acceptor medium by reaction of BoNT-A with Benedict's reagent.Results. It was established that the maximum concentration of BoNT-A diffused into the acceptor medium from the blend of the test substance with tizol after nine hours. The area under the curve for dialysis of BoNT-A + T exceeds the area under the curve of pure BoNT-A by almost 20%, suggesting an improvement in the drug's bioavailability when blended with tizol.Conclusion. Based on our experiment, it was found out that the BoNT-A + T has greater bioavailability than a solution of pure BoNT-A. However, the diffusion rate of the component mixture is sufficiently low.

Differences in bladder neck angles between female patients with overactive bladders and healthy peers.

The aim of this study was to compare the differences between angles of bladder neck in girls with overactive bladder and those in healthy ones using transabdominal ultrasonography. This study consists of 28 girls complicated with overactive bladder (Group I) and 40 healthy girls (Group II). The anteroposterior vesical wall angle (APVA), urethroposterior vesical wall angle (UPVA), urethroanterior vesical wall angle (UAVA), thickness of bladder mucosa, distance of urethral orifices, and distance between ureter and urethra orifice were measured in supine position using transabdominal ultrasonography. The results were compared between the two groups. UAVA in Group I was higher than Group II (135.2 ± 12.2 mm vs. 117.4 ± 14.0 mm; p = 0.009). UPVA was smaller in Group I than Group II (114.6 ± 19.5 mm vs. 135.3 ± 16.5 mm; p = 0.014). The distance between the ureteral orifices was 31.8 ± 8.5 mm in Group I and 17.0 ± 4.1 mm in Group II (p < 0.001). There was no statistically significant difference between groups in terms of APVA, bladder mucosa thickness, and distance between ureter and urethra orifice (p > 0.05). Bladder neck dynamics may play an important role in overactive bladder pathophysiology due to differences in UPVA, UAV, and location of ureteral orifices in this patient population.

Endoscopic diagnosis of an obstructive fungal ball in the urethra of a dog

AbstractA 1‐year‐old, male, neutered German shepherd dog was presented for a chronic atraumatic non‐healing fracture of the right accessory carpal bone, stranguria and polyuria/polydipsia. Biochemistry and urinalysis showed azotaemia. Ultrasound and computed tomography of the abdomen both demonstrated bilateral renal infarcts with pyelectasia, bilateral ureteral dilation and bladder distension. Cystoscopy of the bladder identified a fungal ball obstructing the pelvic urethral sphincter, which was adhered to the bladder mucosa in the region of the ureterovesicular junction. The obstruction was traversed endoscopically, but could not be removed transurethrally. The combination of elevated serum galactomannan titres (6.4) and Aspergillus terreus cultured from urine, confirmed a diagnosis of disseminated aspergillosis. The dog was euthanased due to poor quality of life, guarded prognosis and lengthy timeframe before an expected medical response. This is the first case report describing Aspergillus fungal balls in a dog causing partial urethral and bilateral ureteral obstruction, identified using cystoscopy.

NOVEL SIMPLEXVIRUS (SIMPLEXVIRUS DOLICHOTINEALPHA1) ASSOCIATED WITH FATALITY IN FOUR PATAGONIAN MARA (DOLICHOTIS PATAGONUM).

Four of seven Patagonian maras (Dolichotis patagonum) at a zoological institution developed acute neurologic signs that progressed to tetraparesis and death. All affected were young adult females (10 mon-5 yr old) that presented over 11 d. Clinical signs were rapidly progressive and unresponsive to supportive therapies. Two of the four individuals were found deceased 4 d after hospitalization. Two individuals were euthanized due to poor prognosis and decline after 6 and 8 d, respectively. Simultaneously, an additional mara developed mild and self-resolving clinical signs, including a kyphotic gait and paraparesis. On gross examination, there were widespread petechiae and ecchymoses of the skeletal muscle, myocardium, skin, pericardium, urinary bladder mucosa, and spinal cord. On histopathology, all animals had necrotizing myelitis and rhombencephalitis, with intranuclear viral inclusions in three individuals. Electron microscopy confirmed herpesviral replication and assembly complexes in neurons and oligodendrocytes. Consensus PCR performed on spinal cord, brainstem, or cerebellum revealed a novel Simplexvirus most closely related to Simplexvirus leporidalpha 4. The virus was amplified and sequenced and is referred to as Simplexvirus dolichotinealpha1. It is unknown whether this virus is endemic in Patagonian mara or whether it represents an aberrant host species. Clinicians should be aware of this virus and its potential to cause severe, rapidly progressive, life-threatening disease in this species.

A four-gene model for prognostic prediction in bladder urothelial carcinoma

BackgroundBladder urothelial carcinoma (BLCA) is one of the most common malignant tumors in urinary system worldwide. High possibility of recurrence and progression leads to poor prognosis, revealing the significant role of long-term postoperative monitoring to the patients. However, effective noninvasive diagnosis is currently limited. Materials and methodsDifferentially expressed genes (DEGs) were analyzed using R-packages. Functional enrichment analyses were performed on Metascape. The prognostic model was established by multi-step cox regression and evaluated by survival plots and receiver operating characteristic (ROC) curves. The nomogram was then constructed based on three identified prognostic factors. C-index and calibration curves were calculated to testify the capacity for predicting survival possibility of BLCA patients. The transcription levels of model genes were further verified in a gemcitabine-resistant bladder cancer cell line T24 (TGR) by quantitative real-time PCR (qRT-PCR). Results360 genes were differentially expressed between BLCA and normal bladder mucosae simultaneously in three GEO datasets, of which 59 were up-regulated and 301 were down-regulated. 159 prognostic genes were obtained from DEGs. Lasso and multivariate cox regression were conducted in sequence and the prognostic model was eventually optimized to four genes (EHBP1, RHOJ, FASN, STXBP6). Survival analyses demonstrated that the overall survival (OS) of patients in high-risk group was significantly shorter than that in low-risk group. The area under the curve (AUC) values of 3–5 years survival were basically above 0.7. Moreover, cox regression analyses showed that age, T stage and risk score were independent indicators for BLCA prognosis. For further clinical application, a nomogram was then constructed by integrating these factors. The C-index (0.72, CI 95 %, 0.669–0.775) and calibration curves demonstrated the good performance of nomogram. Importantly, the mRNA level of model genes was significantly up-regulated in TGR compared to T24, indicating a better prediction for chemotherapy-resistant BLCA patients. ConclusionCollectively, our findings suggest a novel four-gene predictive model for BLCA prognosis. It is expected to provide a valuable reference for prognostic evaluation and treatment in BLCA patients.

Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models.

It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments' treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p=0.0007, mean VV; p=0.0032, respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p < 0.0001, 1.0% AA: p < 0.0001). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency.

Secondary Analysis of Interstitial Cystitis/Bladder Pain Syndrome Patients Enrolled in a Recurrent Urinary Tract Infection Prevention Study Provides a Novel Paradigm for Etio-Pathogenesis and Practical Management of This Infection Phenotype.

A subset of interstitial cystitis/bladder pain syndrome (IC/BPS) patients experience recurrent urinary tract infection (rUTI) associated with symptom flares. Recurrent UTI subjects with associated IC/BPS were enrolled in the first North American early clinical experience trial evaluating a new sublingual UTI preventative vaccine, MV140. It has been shown that women with rUTI develop an imbalance in the T helper 1 and 2 (Th2 over-expression) in the bladder mucosa. Our hypothesis-generating secondary analysis will suggest that this infection subcategory of IC/BPS patients develop a similar imbalance of Th1-Th2 response type to bacteria present in their urinary microbiome, leading to a bladder hypersensitivity that responds to mucosal immune modulation. Female participants with ≥3 documented UTI/year underwent a 3-month vaccination treatment period with a 9-month efficacy period after completion of vaccine treatment (total 12 months). There were no exclusion criteria for subjects in relation to baseline urinary symptoms and/or discomfort/pain. Primary outcome was no UTI following vaccination. Secondary outcomes included change in UTI incidence, overall patient-reported subjective global assessment (SGA responder defined as moderately or markedly improved on 7-point scale), and safety. Sixteen subjects with IC/BPS-related symptoms and rUTI (mean age 47; range 23-74 years; mean number of UTI episodes in previous year 6.1 +/- 4.2) were eligible to be included in the Health Canada-approved MV140 vaccine study for prevention of rUTI. All subjects completed the 3-month vaccination period. One subject was lost to follow-up after their 6-month visit. Six subjects were UTI-free, while all 16 subjects had a reduction in UTI episodes compared to the year pre-vaccination. The total post-vaccination reduction in UTI episodes compared to pre-vaccination was 80% (0.1 UTI/subject/month from 0.5 UTI/subject/month, respectively). At 12 months, 13 subjects (81%) were SGA responders (moderately or markedly improved), and the responders reported a reduction in IC/BPS symptoms, with 8 subjects reporting significant or almost complete resolution of their specific long-term bladder discomfort/pain and bothersome urinary frequency or urgency. Four subjects reported mild and self-limited adverse events during vaccination period, but none were related to MV140 vaccine. Sublingual MV140 vaccine in IC/BPS patients with rUTI not only achieved UTI-free or reduced UTI incidence status but also, after approximately 9 months post vaccination, resolution of patients' long-term treatment-refractory IC/BPS symptoms. This suggests some cases of IC/BPS may be etiologically based on Th2-driven hypersensitivity to bacteria within or entering the urinary microbiome that responds to a vaccine whose mechanism of action is to normalize or balance the bladder Th1/Th2 mucosal immune system.

Effects of acute hypoxia on contractile responses of the bladder mucosa in vitro

Effects of acute hypoxia on contractile responses of the bladder mucosa in vitro

Transurethral Resection of Necrotic Tissue in the Bladder Caused by Emphysematous Cystitis

Emphysematous cystitis is a relatively rare form of urinary tract infection. A 72-year-old man with diabetes mellitus and long-term indwelling urethral catheterization was diagnosed with emphysematous cystitis. The clinical findings were resolved by conservatively managing the patient with antibiotics. However, cystoscopy subsequently revealed a yellowish-white soft tissue mass in the bladder, which was unlikely to be a bladder tumor. The mass could not be removed easily and frequently caused urinary catheter obstruction. We successfully removed this mass by performing transurethral resection twice. Through histopathological examination, the mass was identified as necrotic tissue comprising bacteria, fibrin, and suspected bladder mucosa.

Microbiome Sex-Related Diversity in Non-Muscle-Invasive Urothelial Bladder Cancer.

Sex-specific discrepancies in bladder cancer (BCa) are reported, and new studies imply that microbiome may partially explain the diversity. We aim to provide characterization of the bladder microbiome in both sexes diagnosed with non-muscle-invasive BCa with specific insight into cancer grade. In our study, 16S rRNA next-generation sequencing was performed on midstream urine, bladder tumor sample, and healthy-appearing bladder mucosa. Bacterial DNA was isolated using QIAamp Viral RNA Mini Kit. Metagenomic analysis was performed using hypervariable fragments of the 16S rRNA gene on Ion Torrent Personal Genome Machine platform. Of 41 sample triplets, 2153 taxa were discovered: 1739 in tumor samples, 1801 in healthy-appearing bladder mucosa and 1370 in midstream urine. Women were found to have smaller taxa richness in Chao1 index than men (p = 0.03). In comparison to low-grade tumors, patients with high-grade lesions had lower bacterial diversity and richness in urine. Significant differences between sexes in relative abundance of communities at family level were only observed in high-grade tumors.

A novel magnetic compression technique for establishment of a vesicovaginal fistula model in Beagle dogs

Vesicovaginal fistula lacks a standard, established animal model, making surgical innovations for this condition challenging. Herein, we aimed to non-surgically establish vesicovaginal fistula using the magnetic compression technique, and the feasibility of this method was explored using eight female Beagle dogs as model animals. In these dogs, cylindrical daughter and parent magnets were implanted into the bladder and vagina, respectively, after anesthesia, and the positions of these magnets were adjusted under X-ray supervision to make them attract each other, thus forming the structure of daughter magnet-bladder wall-vaginal wall-parent magnet. Operation time and collateral damage were recorded. The experimental animals were euthanized 2 weeks postoperatively, and the vesicovaginal fistula gross specimens were obtained. The size of the fistula was measured. Vesicovaginal fistula was observed by naked eye and under a light microscope. Magnet placement was successful in all dogs, and remained in the established position for the reminder of the experiment. The average operation time was 14.38 min ± 1.66 min (range, 12–17 min). The dogs were generally in good condition postoperatively and were voiding normally, with no complications like bleeding and urine retention. The magnets were removed from the vagina after euthanasia. The vesicovaginal fistula was successfully established according to gross observation, and the fistula diameters were 4.50–6.24 mm. Histological observation revealed that the bladder mucosa and vaginal mucosa were in close contact on the internal surface of the fistula. Taken together, magnetic compression technique is a simple and feasible method to establish an animal model of vesicovaginal fistula using Beagle dogs. This model can help clinicians study new surgical techniques and practice innovative approaches for treating vesicovaginal fistula.

Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury.

Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI). Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated. In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased,and bladder MAGL was decreased after MAGL inhibitor treatment. MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.

Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic Escherichia coli.

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic Escherichia coli (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.