Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry.

PURPOSE: Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles. MATERIALS AND METHODS: Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion. RESULTS: The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88-0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column. CONCLUSIONS: Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.

Chlorogenic Acid Intravesical Therapy Changes Acute Voiding Behavior of Systemic Lipopolysaccharide Inflammation-Induced Cystitis Bladder in Mice.

This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson's trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications.

Prediction of clinically significant prostate cancer through urine metabolomic signatures: A large-scale validated study.

PURPOSE: Currently, there are no accurate markers for predicting potentially lethal prostate cancer (PC) before biopsy. This study aimed to develop urine tests to predict clinically significant PC (sPC) in men at risk. METHODS: Urine samples from 928 men, namely, 660 PC patients and 268 benign subjects, were analyzed by gas chromatography/quadrupole time-of-flight mass spectrophotometry (GC/Q-TOF MS) metabolomic profiling to construct four predictive models. Model I discriminated between PC and benign cases. Models II, III, and GS, respectively, predicted sPC in those classified as having favorable intermediate risk or higher, unfavorable intermediate risk or higher (according to the National Comprehensive Cancer Network risk groupings), and a Gleason sum (GS) of ≥ 7. Multivariable logistic regression was used to evaluate the area under the receiver operating characteristic curves (AUC). RESULTS: In Models I, II, III, and GS, the best AUCs (0.94, 0.85, 0.82, and 0.80, respectively; training cohort, N = 603) involved 26, 24, 26, and 22 metabolites, respectively. The addition of five clinical risk factors (serum prostate-specific antigen, patient age, previous negative biopsy, digital rectal examination, and family history) significantly improved the AUCs of the models (0.95, 0.92, 0.92, and 0.87, respectively). At 90% sensitivity, 48%, 47%, 50%, and 36% of unnecessary biopsies could be avoided. These models were successfully validated against an independent validation cohort (N = 325). Decision curve analysis showed a significant clinical net benefit with each combined model at low threshold probabilities. Models II and III were more robust and clinically relevant than Model GS. CONCLUSION: This urine test, which combines urine metabolic markers and clinical factors, may be used to predict sPC and thereby inform the necessity of biopsy in men with an elevated PC risk.

Insight into SLC9A3 deficiency-mediated micturition dysfunction caused by electrolyte imbalance.

BACKGROUND: Solute carrier family nine isoform 3 (SLC9A3) is an Na+/H+ exchanger that regulates Ca2+ homeostasis. SLC9A3 is largely involved in the transepithelial absorption of Na+/H+ and frequently functions in pair with a Cl-/HCO3- exchanger. OBJECTIVE: To investigate the impact and pathophysiological mechanisms of long-term SLC9A3 deficiency on lower urinary tract symptoms (LUTS) in a mouse model MATERIALS AND METHODS: Slc9a3 knockout and wild-type mice (average >6 months) were used. The effects of SLC9A3 depletion on bladder and urethral functions and effectiveness of voiding were assessed using a cystometrogram (CMG). Histology, blood electrolytes, and gene expression were also analyzed. RESULTS: The SLC9A3-deficient mice had smaller gross bladders than the wild-type mice. The CMG analysis revealed normal peak micturition pressure, higher threshold pressure, short intercontraction interval, less voided volume, and poor compliance in the SLC9A3-deficient mice, similar to clinical LUTS. Histological analysis revealed loose detrusor muscle and loss of transformability of the urothelium in the SLC9A3-deficient mice. Masson's trichrome analysis revealed severe collagen deposition in the detrusor muscle. Immunofluorescence staining also demonstrated a significant decrease in cytokeratins 5 and 20. Gene and protein expression analyses confirmed that SLC9A3 does not act directly on bladder tissue. Homeostasis was correlated with bladder dysfunction in the SLC9A3-deficient mice. DISCUSSION: Fibrosis and collagen deposition in the bladder of the SLC9A3-deficient mice is due to bladder inflammation because of decreased blood flow and deregulated systemic homeostasis. Long-term SLC9A3 depletion causes progressive bladder dysfunction, similar to human LUTS. CONCLUSION: Electrolyte imbalance causes SLC9A3 deficiency-mediated progressive micturition dysfunction.

Effects of platelet-rich plasma glue placement at the prostatectomy site on erectile function restoration and cavernous nerve preservation in a nerve-sparing prostatectomy rat model.

BACKGROUND: Despite the widespread use of nerve-sparing prostatectomy techniques, the incidence of post-operative erectile dysfunction (ED) remains high. Early intracavernous (IC) injection of platelet-rich plasma (PRP) after nerve crushing improves erectile function (EF) in rats by promoting cavernous nerve (CN) regeneration and preventing structural changes in the corpus cavernosum. However, the neuroprotective effects of the in situ application of PRP glue in rats after CN-sparing prostatectomy (CNSP) remain unclear. AIM: This study aimed to investigate the effects of PRP glue treatment on EF and CN preservation in rats after CNSP. METHODS: After prostatectomy, male Sprague-Dawley rats were treated with PRP glue, IC PRP injection, or their combination. The intracavernous pressure (ICP), mean arterial pressure (MAP), and CN preservation status in the rats were evaluated after 4 weeks. Results were corroborated using histology, immunofluorescence, and transmission electron microscopy. RESULTS: The PRP glue-treated rats showed 100% CN preservation and significantly higher ICP responses (the ratio of maximum ICP to MAP (0.79 ± 0.09)) than the CNSP rats (the ratio of maximum ICP to MAP (0.33 ± 0.04)). PRP glue also significantly increased neurofilament-1 expression, indicating its positive effect on the CNs. Furthermore, this treatment significantly increased the expression of α-smooth muscle actin. Electron micrographs revealed that PRP glue preserved the myelinated axons and prevented atrophy of the corporal smooth muscle by maintaining the adherens junctions. CONCLUSIONS: These results indicate that PRP glue is a potential solution for EF preservation by neuroprotection in patients with prostate cancer who are likely to undergo nerve-sparing radical prostatectomy.

Consensus of Experts on the Treatment of Sexual Dysfunction after Surgery for Prostate Cancer in Taiwan.

According to the Taiwan Cancer Report, in 2018, prostate cancer was one of the top five cancers reported in men. Each year, many patients with prostate cancer undergo radical prostatectomy (RP) therapy. One of the most common RP complications is erectile dysfunction (ED). Although consensus guidelines for the management of sexual dysfunction after prostate cancer surgery have been developed for many Western and Asian countries, no such clinical practice guidelines have been developed for Taiwan. The consensus opinions expressed in this article were discussed by numerous experienced physicians in Taiwan, based on both existing international guidelines and their individual experiences with clinical trials and providing advice to clinical physicians on how to inform patients of the risk of ED prior to surgery. This review also discusses how recovery and rehabilitation may be affected by socioeconomic status, the existence of an intimate relationship, comorbidities, or the need for cancer adjuvant therapy and how to determine rehabilitation goals and provide appropriate treatments to assist in the recovery of both short- and long-term sexual function.

Current Surgical Treatment for Neurogenic Lower Urinary Tract Dysfunction in Patients with Chronic Spinal Cord Injury.

This study aimed to present a comprehensive literature review of the efforts of a spinal cord injury workgroup in Taiwan regarding urologic surgery for neurogenic lower urinary tract dysfunction (NLUTD) in patients with chronic spinal cord injury (SCI). Surgical procedures should be viewed as a final option for managing patients with SCI who have persistent symptoms and complications that cannot be resolved by other means. Surgeries can be grouped according to their purpose: reducing bladder pressures, reducing urethra resistance, increasing urethra resistance, and urinary diversion. The choice of surgery depends on the type of LUTD based on urodynamic tests. Additionally, cognitive function, hand motility, comorbidities, efficacy of surgery, and related complications should be considered.

Development of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) for Women with Interstitial Cystitis.

Background and Objectives: Women with interstitial cystitis (IC) suffer from spontaneous serious bladder pain symptoms without immediate resolution. Women with IC may lack knowledge of how to help themselves. Therefore, a measurement of IC self-help and medical-resource-seeking for women with IC is needed. Materials and Methods: This study recruited 100 women with IC from a teaching hospital in Northern Taiwan. The reliability and validity of the Interstitial Cystitis Self-Help and Medical Resources Scale (ICSR) were assessed using expert validity, confirmatory factor analysis (CFA) to test the construct validity, composite reliability to evaluate the internal consistency, and item analysis to test the discrimination validity of each item. Results: The results showed that the ICSR had accurate goodness-of-fit indices and the component reliability ranged from 0.42 to 0.83, indicating good reliability and validity. Conclusions: The ICSR is recommended for screening the self-help and medical-resource-seeking abilities of women with IC to aid in diagnosing IC and providing more precise medical treatments.

Intracavernous Injection of Platelet-Rich Plasma Therapy Enhances Erectile Function and Decreases the Mortality Rate in Streptozotocin-Induced Diabetic Rats.

Erectile dysfunction (ED) is an agonizing complication of diabetes mellitus (DM) and it is challenging to treat ED in DM patients. Platelet-rich plasma (PRP) is a unique therapeutic strategy comprising intrinsic growth factors. An attempt was made to explore the potentiality of the PRP treatment in DM-induced ED rats in various groups (control, DM-non-ED, DM-ED, and DM-ED treated with PRP). Streptozotocin (STZ) was used to induce DM in rats. The blood glucose levels of the DM rats were maintained at >300 mg/dl. In the 18-week experiment, survival rate, body weight, intracavernous pressure (ICP) variations, and arterial blood pressure were analyzed. The tissue restoration results were validated by histological, immunofluorescence, and transmission electron microscopic analysis. PRP treatment of DM-ED rats significantly increased all parameters of erectile function compared to pre-treatment of PRP and DM-ED treated with vehicle. The histological results revealed that PRP treatment substantially enhanced the regeneration of myelinated nerves and decreased the atrophy of corporal smooth muscle. Notably, the PRP treatment immensely enhanced the survival rate in post-surgery DM-ED rats. These results indicated certain benefits of PRP treatment in delaying damage and preventing post-surgery complications in DM patients. Hence, PRP treatment is a novel multifactorial strategy for DM-ED patients.

Uremic Toxin Indoxyl Sulfate Impairs Hydrogen Sulfide Formation in Renal Tubular Cells.

Hydrogen sulfide (H2S) was the third gasotransmitter to be recognized as a cytoprotectant. A recent study demonstrated that exogenous supplementation of H2S ameliorates functional insufficiency in chronic kidney disease (CKD). However, how the H2S system is impaired by CKD has not been elucidated. The uremic toxin indoxyl sulfate (IS) is known to accumulate in CKD patients and harm the renal tubular cells. This study therefore treated the proximal tubular cells, LLC-PK1, with IS to see how IS affects H2S formation. Our results showed that H2S release from LLC-PK1 cells was markedly attenuated by IS when compared with control cells. The H2S donors NaHS and GYY-4137 significantly attenuated IS-induced tubular damage, indicating that IS impairs H2S formation. Interestingly, IS downregulated the H2S-producing enzymes cystathionine ß-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), and these effects could be reversed by inhibition of the IS receptor, aryl hydrocarbon receptor (AhR). As transcription factor specificity protein 1 (Sp1) regulates the gene expression of H2S-producing enzymes, we further showed that IS significantly decreased the DNA binding activity of Sp1 but not its protein expression. Blockade of AhR reversed low Sp1 activity caused by IS. Moreover, exogenous H2S supplementation attenuated IS-mediated superoxide formation and depletion of the cellular glutathione content. These results clearly indicate that IS activates AhR, which then attenuates Sp1 function through the regulation of H2S-producing enzyme expression. The attenuation of H2S formation contributes to the low antioxidant defense of glutathione in uremic toxin-mediated oxidative stress, causing tubular cell damage.

B6 Mouse Strain: The Best Fit for LPS-Induced Interstitial Cystitis Model.

Interstitial cystitis (IC) is a chronic inflammatory disease characterized by bladder pain and increased urinary frequency. Although the C57BL/6J (B6) and FVB/NJ (FVB) mouse strains are commonly used as animal models for studies involving the urinary system, few reports have compared their lower urinary tract anatomy, despite the importance of such data. Our study aimed to characterize bladder function changes in FVB and B6 mouse strains with lipopolysaccharide (LPS)-induced IC, to understand mouse model-based bladder research. The bladder function parameters were measured by cystometrogram. Histological assay was examined by hematoxylin and eosin stain, Masson's trichrome stain, and immunofluorescence staining. Results indicated that the two strains in the control group exhibited different bladder structures and functions, with significant anatomical differences, including a larger bladder size in the FVB than in the B6 strain. Furthermore, cystometry tests revealed differences in bladder function pressure. LPS-treated B6 mice presented significant changes in peak pressure, with decreased intercontraction intervals; these results were similar to symptoms of IC in humans. Each strain displayed distinct characteristics, emphasizing the care required in choosing the appropriate strain for bladder-model studies. The results suggested that the B6 mouse strain is more suitable for IC models.

High Tumor Burden Predicts Poor Response to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer Patients.

To assess the predictive value of tumor burden on the biochemical response, and radiological response in Taiwanese metastatic castration-resistant prostate cancer (mCRPC) patients receiving enzalutamide. The mCRPC patients treated with enzalutamide were recruited from three hospitals. High tumor burden (HTB) was classified as metastases at either appendicular bone or visceral organ. Good prostate-specific antigen (PSA) response was defined as PSA reduction of 80%. In this cohort, there were 104 (54.2%) HTB patients and 88 (45.8%) with low tumor burden (LTB). Compared to LTB patients, fewer HTB patients had good PSA response (odds ratio: 0.43, range: 0.22-0.87, p = 0.019) and fewer radiological response (complete and partial remission) (odds ratio: 0.78, range: 0.36-1.68, p = 0.52) to enzalutamide. The disease control rate which also contained stable disease, was still lower in HTB (76.0%) than LTB group (92.9%, OR: 0.24, range: 0.07-0.77, p = 0.016) in the multivariable model. In addition, HTB patients had significantly shorter progression-free survival duration than did LTB patients (median: 8.3 vs. 21.6 months, log-rank test p = 0.003) in the univariable analysis. The tumor burden before the use of enzalutamide was associated with treatment outcomes. HTB reduced PSA response rate, radiological response rate and progression-free survival duration.

Intravesical Instillation of Norketamine, a Ketamine Metabolite, and Induced Bladder Functional Changes in Rats.

This study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical instillation of ketamine and norketamine by mini-osmotic pump, which was placed in subcutaneous space, daily for 24 h for 4 weeks. After 4 weeks, all rats were subjected to bladder functional tests. The bladders were collected for histological and pathological evaluation. Compared to control, ketamine treatment demonstrated an increase in the bladder weight, high bladder/body coefficient, contractive pressure, voiding volume, collagen deposition, reduced smooth muscle content, damaged glycosaminoglycan layer, and low bladder compliance. Compared to ketamine, norketamine treatment showed more severe collagen deposition, smooth muscle loss, damaged glycosaminoglycan layer, and increased residual urine. Intravesical administration of ketamine and norketamine induced cystitis with different urodynamic characteristics. Norketamine treatment caused more severe bladder dysfunction than ketamine treatment. Direct treatment of the bladder with norketamine induced symptoms more consistent with those of bladder outlet obstruction than ketamine cystitis. Detailed studies of cellular mechanisms are required to determine the pathogenesis of ketamine cystitis.

CXCL5 Cytokine Is a Major Factor in Platelet-Rich Plasma's Preservation of Erectile Function in Rats After Bilateral Cavernous Nerve Injury.

BACKGROUND: The neuro-protective and tissue-protective properties of platelet-rich plasma (PRP) have been demonstrated through treating bilateral cavernous nerve (CN) injury in rats, although the underlying mechanisms have not been fully clarified. AIM: To determine factors released from PRP and explore their role in mediating preservation of erectile function (EF) in a rat model of CN injury. METHODS: Male Sprague-Dawley rats (aged 10 weeks) were used in this study. 6 rats were used to obtain blood for PRP and whole plasma preparation. We probed samples using a cytokine antibody array and performed enzyme-linked immunosorbent assay (ELISA). We determined the expression patterns of C-X-C motif chemokine ligand 5 (CXCL5) and receptors in the major pelvic ganglion (MPG) and corpus cavernosum via immunostaining. 32 rats were divided into 4 groups based on the type of injection received: (i) sham, (ii) vehicle, (iii) 400 µL of PRP, and (iv) 30 ng/kg of CXCL5. Groups 2-4 were subjected to bilateral CN crush (BCNC) injury. 4 weeks later, EF was assessed by CN electrostimulation, and CNs and penile tissue were collected for histological analysis. OUTCOME: Cytokine antibody array, ELISA, erectile response, and immunofluorescence staining readings. RESULTS: The PRP contained high levels of CXCL5. MPG neurons expressed CXCL5 and CXCR2. PRP intracavernous injection stabilized CXCR2 and increased CXCL5 expression in the MPG after BCNC, thus enhancing neuroprotection. CXCL5 injection improved BCNC-induced erectile dysfunction by preventing smooth muscle atrophy. CLINICAL IMPLICATIONS: The therapeutic efficacy of PRP in CN injury-induced erectile dysfunction may arise from the synergy among multiple biomolecules. Our study serves as a basis for future studies on PRP formulation to provide safe and effective medications for the maintenance of EF after radical prostatectomy in patients with prostate cancer. STRENGTHS & LIMITATIONS: A strength of our study is that our model was able to isolate the role of cytokines, specifically CXCL5, as part of the mechanism responsible for PRP's protective properties. However, the rat cytokine array provided limited experimental targets. The rats used were not at the age corresponding to prostate cancer patients in clinical settings. Our study did not explore CXCL5 blocking in the PRP group. Finally, the main protein quantification results by western blotting were hampered because of small tissue samples. CONCLUSIONS: This study provides evidence for the role of CXCL5 and CXCR2 as mediators of PRP effects in the preservation of EF after CN injury. Wu YN, Liao CH, Chen KC, et al. CXCL5 Cytokine Is a Major Factor in Platelet-Rich Plasma's Preservation of Erectile Function in Rats After Bilateral Cavernous Nerve Injury. J Sex Med 2021;18:698-710.

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders.

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment.

Self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis/painful bladder syndrome.

BACKGROUND: This study aims to investigate the self-perception of symptoms, medical help seeking, and self-help strategies of women with interstitial cystitis (IC). METHODS: A mixed method of qualitative and quantitative approaches was employed. The qualitative approach used in-depth interviews about the subjective experience of symptoms, medical help seeking, and self-help strategies for their IC. The quantitative inquiry was conducted by a yes or no response to the question "Did self-perceived severe symptoms of IC interfere with your daily life?" A loglinear model was applied to investigate the associations between possible factors. RESULTS: This study recruited 68 women aged 20 to 69 years, of whom 22 were interviewed for qualitative data. About 72.1% of the women responded that self-perceived severe IC symptoms interfered with their daily life. A significant negative association between employment and self-perceived severe IC symptoms (P < .05) was observed. Qualitative results revealed three important themes: (1) bothersome symptoms-all-day bladder pain and lower urinary tract symptoms and deteriorated quality of life, (2) medical help seeking-exhaustion and frustration, (3) self-help strategies-coexisting with IC or feeling helpless. CONCLUSIONS: IC women feel exhausted and frustrated by seeking medical attention for this incurable disease for a long time. IC women have troubled and uneasy daily lives. Being employed or engaging in activities can divert attention to alleviate symptoms. IC patient support groups allow patients to share their self-help experiences with interdisciplinary medical teams to provide physical and psychological treatment.

Smooth Muscle Progenitor Cells Preserve the Erectile Function by Reducing Corporal Smooth Muscle Cell Apoptosis after Bilateral Cavernous Nerve Crush Injury in Rats.

Radical prostatectomy causes erectile dysfunction (ED) and irreversible morphologic changes, including induction of endothelial and smooth muscle cell (SMC) apoptosis in the corpus cavernosum (CC). The injection of smooth muscle progenitor cells (SPCs) thickens the vascular intima and has demonstrated therapeutic benefit in cardiovascular disease animal. Herein, we investigated the effect of SPCs on the recovery of erectile function (EF) in rat models with bilateral cavernous nerve (CN) injury. Twenty-four male Sprague-Dawley rats were randomized into sham, vehicle only, or SPC treatment groups. Rats in the SPC treatment and vehicle groups were subjected to bilateral CN injury before intracavernosal injection. Intracavernosal injections of SPCs increased all EF parameters at day 28 after injury and simultaneously reduced apoptosis of the SMCs. Ultrastructural analysis revealed that SPCs maintained the integrity of the CC by preserving the structure of the adherens junctions. Tracking transplanted SPCs labeled with EdU showed that transplanted SPCs remained in the CC 28 days after treatment. Intracavernosal SPC injection restored EF after bilateral CN injury by reducing SMC apoptosis, which favored the maintenance of the structure of adherens junctions and regulated the stability of corporal vessels. These findings demonstrate the therapeutic potential of SPCs for treating ED in humans.

Can Botulinum Toxin A Still Have a Role in Treatment of Lower Urinary Tract Symptoms/Benign Prostatic Hyperplasia Through Inhibition of Chronic Prostatic Inflammation?

Patients with benign prostatic hyperplasia (BPH) can exhibit various lower urinary tract symptoms (LUTS) owing to bladder outlet obstruction (BOO), prostatic inflammation, and bladder response to BOO. The pathogenesis of BPH involves an imbalance of internal hormones and chronic prostatic inflammation, possibly triggered by prostatic infection, autoimmune responses, neurogenic inflammation, oxidative stress, and autonomic dysfunction. Botulinum toxin A (BoNT-A) is well recognized for its ability to block acetylcholine release at the neuromuscular junction by cleaving synaptosomal-associated proteins. Although current large clinical trials have shown no clinical benefits of BoNT-A for the management of LUTS due to BPH, BoNT-A has demonstrated beneficial effects in certain subsets of BPH patients with LUTS, especially in males with concomitant chronic prostatitis/chronic pelvic pain syndrome and smaller prostate. We conducted a review of published literature in Pubmed, using Botulinum toxin, BPH, BOO, inflammation, LUTS, and prostatitis as the key words. This article reviewed the mechanisms of BPH pathogenesis and anti-inflammatory effects of BoNT-A. The results suggested that to achieve effectiveness, the treatment of BPH with BoNT-A should be tailored according to more detailed clinical information and reliable biomarkers.

Early renal arterial rupture and arterial pseudoaneurysm in graft kidneys from the same deceased donor.

Vascular complications are serious problems after kidney transplantation. An aneurysm or rupture in a graft artery is a rare but potentially devastating complication, which may lead to renal function impairment, graft loss, or even death. In this paper, we present two rare vascular complications in the early postoperative course after renal transplantation from the same deceased donor. In the first case, a 49-year-old woman who had spontaneous graft arterial rupture 13 days after kidney transplantation presented with sudden distension in the right lower abdomen. In the second case, a 56-year-old woman recipient with a graft renal arterial pseudoaneurysm presented with decreased urine output and deteriorating renal function 32 days after transplantation. Immediate surgical repair was performed, and fibrin sealant was applied to strengthen the fragile renal arterial wall. Although the function of both graft kidneys recovered well after surgery, the first graft kidney was removed 2 months later because of repeated fungal and bacterial infections. Aggressive surgical reconstruction may preserve graft kidneys in patients with vascular complications after kidney transplantation, but recovery of the graft condition remains a demanding challenge in renal transplantation.

DAPK and CIP2A are involved in GAS6/AXL-mediated Schwann cell proliferation in a rat model of bilateral cavernous nerve injury.

PURPOSE: Impotence is one of the major complications occurring in prostate cancer patients after radical prostectomy (RP). Self-repair of the injured nerve has been observed in animal models and in patients after RP. However, the downstream signalling is not well documented. Here, we found that the DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. MATERIALS AND METHODS: The 3 groups were a sham group, a 14-day post-bilateral cavernous nerve injury (BCNI) group and a 28-day post-BCNI group. Erectile function was assessed and immunohistochemistry was performed. The rat Schwann cell RSC96 line was chosen for gene knockdown, cell viability, western blot, immunofluorescence and co-immunoprecipitation assays. RESULTS: The intracavernosal pressure was low on the 14th day after BCNI and partially increased by the 28th day. GAS6 and p-AXL expression gradually increased in the cavernous nerve after BCNI. RSC96 cells incubated with a GAS6 ligand showed increased levels of p-ERK1/2 and p-AKT. Moreover, DAPK and CIP2A.p-AXL and p-DAPK and CIP2A complexes were identified by both immunoblotting and co-immunoprecipitation. CONCLUSION: The DAPK/CIP2A complex is involved in GAS6/AXL-related Schwann cell proliferation. CIP2A inhibits PP2A activity, which results in p-DAPK(S308) maintenance and promotes Schwann cell proliferation. CIP2A is a potential target for the treatment of nerve injury after RP.