Cytosine Deaminase-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhance the Inhibitory Effects of Fluorocytosine on Tumor Growth in Castration Resistant Prostate Cancer.

A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells (hTERT-ADSC.CD) to suppress CRPC. A lentiviral vector encoding a bacterial CD gene was used to transfect and to generate the hTERT-ADSC.CD line. The ability of the cells to migrate selectively towards malignant cells was investigated in vitro. PC3 and hTERT-ADSC.CD cells were co-cultured. hTERT-ADSC.CD and 1 × 106 PC3 cells were administered to nude mice via intracardiac and subcutaneous injections, respectively, and 5-FC was given for 14 days. hTERT-ADSC.CD were successfully engineered. Enhanced in vitro hTERT-ADSC.CD cytotoxicity and suicide effect were evident following administration of 5 µM 5-FC. hTERT-ADSC.CD, together with 5-FC, augmented the numbers of PC3 cells undergoing apoptosis. In comparison to controls administered hTERT-ADSC.CD monotherapy, hTERT-ADSC.CD in combination with 5-FC demonstrated a greater suppressive effect on tumor. In CPRC-bearing mice, tumor suppression was enhanced by the combination of CD-overexpressing ADSC and the prodrug 5-FC. Stem cells exhibiting CD gene expression are a potential novel approach to treatment for CRPC.

Enhanced Hypoxia-Associated Genes in Impaired Contractility From Bladder Outlet Obstruction.

BACKGROUND: Hypoxia damages the bladder wall and contributes to the initiation of bladder dysfunction. The change of hypoxia is not well known in impaired bladder contractility caused by long-term bladder outlet obstruction (BOO). We aimed to find out whether hypoxia of bladder tissue is present and what signaling mechanisms are involved in the decompensated bladder in BOO. METHODS: Twenty 6-week-old female Sprague-Dawley rats were divided into 2 groups, 10 rats each: group 1, sham operation; group 2, BOO for 8 weeks. Eight weeks after the onset of BOO, we did cystometric evaluation and processed polymerase chain reaction (PCR) array for hypoxia pathway using bladder tissues. The PCR array consists of 84 genes known to be involved in the hypoxic response, cell differentiation, and metabolism. We did quantitative PCR (qPCR) and immunohistochemical staining of bladder tissue for hypoxia. RESULTS: Eight genes were at least 2-fold upregulated and 3 genes were at least 2-fold downregulated in BOO group, compared with the sham operation group. The up-regulated genes (fold change) belonging to the hypoxia-inducible factor (HIF) 1 interactor included Cdkn2a (11.0), and the down-regulated genes belonging to HIF and co-transcription factors included Hif3a (-39.6) and Per1 (-5.1) by BOO. Genes influenced each other by means of TGFß1, TNF, and TP53. CONCLUSION: Hypoxia genes were increased in impaired contractility because of long-term BOO. The gene expression profiles could explain the molecular mechanisms of hypoxia in impaired contractility because of long-term BOO.

Clinical efficacy of retrograde urethrography-assisted urethral catheterization after failed conventional urethral catheterization.

BACKGROUND: Several approaches for urethral catheterization after the failure of initial urethral catheterization have been introduced. However, standard procedures regarding what should be done after failed conventional urethral catheterization have been not established. Therefore, we investigated the clinical efficacy of retrograde urethrography (RGU)-assisted urethral catheterization after failed conventional urethral catheterization. METHODS: Between July 2015 and July 2018, 136 patients who underwent RGU-assisted urethral catheterization after failed conventional urethral catheterization were included in this retrospective study. Patients' clinical data, such as age, catheterization site, and previous history of urologic operations, were collected and assessed via chart review. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for the failure of this procedure. RESULTS: Of the 136 patients, 94 (69.1%) experienced successful RGU-assisted urethral catheterization. Having a previous history of urologic operations, such as urethrotomy and transurethral prostatectomy, was identified as an independent predictive factor for the failure of RGU-assisted urethral catheterization (odds ratio = 9.453, 95% confidence interval = 2.703-33.063, p < 0.001). CONCLUSIONS: RGU-assisted urethral catheterization can be one of the modalities for providing successful catheterization after failed conventional urethral catheterization. We believe that RGU-assisted urethral catheterization can be an effective procedure if patients have no previous history of urologic operations, such as urethrotomy and transurethral prostatectomy. Trial registration Soonchunhyang university institutional review board approval (No. 2018-08-021).

Comparison of treatment outcomes according to output voltage during shockwave lithotripsy for ureteral calculi: a prospective randomized multicenter study.

PURPOSE: To investigate the effect of fixed versus escalating voltage during SWL on treatment outcomes in patients with ureteral calculi (UC). METHODS: A prospective, randomized, multicenter trial was conducted on 120 patients who were diagnosed with a single radiopaque UC. The patients were randomized into group C (n = 60, constant 13 kV, 3,000 shock wave, 2 Hz) or group E (n = 60, 11.4-12.0-13 kV per 1,000 shock waves, 2 Hz). They were evaluated by plain abdominal radiography and urinalysis at 1 week after a single session of SWL, and repeat SWL was performed if needed. The primary endpoint was stone-free rate at 1 week (SFR1) after SWL. Secondary endpoints were post-SWL visual pain score (VPS), oral analgesic requirements during 1 week, and cumulative SFRs after the second and third sessions of SWL. RESULTS: Groups C and E were well balanced in terms of baseline patients and stone characteristics, including pre-SWL VPS, stone location, and stone size (6.24 ± 1.92 vs. 6.30 ± 2.13 mm). SFR1s were not significantly different between groups C and E (60.0 vs. 68.3%, p = 0.447). Analyses stratified by stone size (<6 vs. ≥6 mm) showed no difference in SFR1 (p = 0.148 vs. 0.808). In the analyses stratified by stone location, group E tended to be more effective in distal UC (81.0 vs. 50.0%, p = 0.052), whereas no difference was seen in proximal UC (p = 0.487). Secondary endpoints were also similar between the two groups. CONCLUSIONS: Our results suggest that voltage escalation during SWL in UC may not provide superior stone fragmentation compared to fixed voltage.

Can we decide the optimal initial treatment for male lower urinary tract symptoms patients with overactive bladder by the most bothersome symptom? A randomized, prospective, open-label study.

OBJECTIVES: To compare the treatment outcome of tamsulosin 0.4 mg (TAM) with or without solifenacin 5 mg (SOL) for the most bothersome symptom in male lower urinary tract symptoms (LUTS) with overactive bladder (OAB). SUBJECTS AND METHODS: Male LUTS/OAB (≥50 years) patients who had a total International Prostate Symptom Score (I-PSS) of ≥12, I-PSS urgency-related question of ≥2, and quality of life (QoL) of ≥3 points were enrolled. Patients who complained of storage symptoms as the most bothersome were included in the 'storage' group. Patients who complained of voiding symptoms as the most bothersome were included in the 'voiding' group. The change in the I-PSS was compared between the two groups 4 weeks after commencing treatment. RESULTS: In the storage group, 172 were able to finish this study (TAM: 88, TAM + SOL: 84). The improvement of I-PSS and QoL with TAM + SOL was significantly greater than with TAM alone (p < 0.001). In the voiding group, 108 were able to finish the study (TAM: 54, TAM + SOL: 54). The improvement of I-PSS and QoL with TAM alone was significantly greater than with TAM + SOL (p < 0.001). CONCLUSIONS: The most bothersome symptom in male LUTS/OAB should be considered when choosing the appropriate medical treatment.

2023 Korean Association of Urogenital Tract Infection and Inflammation guidelines for gonococcal infection.

The incidence of gonorrhea has increased significantly in recent years in the United States, especially among sexually active twenty-year-olds. Although the incidence of gonorrhea has decreased in Korea since the early 2000s, it is still common among people in their twenties. Nucleic acid amplification test (NAAT) is the most sensitive diagnostic test for detecting gonococcal infection. Gram-staining is a simple and useful laboratory test for diagnosing symptomatic male gonococcal urethritis. Although bacterial culture can be used to detect antimicrobial susceptibility, its sensitivity is lower than that of NAAT. Treatment for uncomplicated gonorrhea infection is a single intramuscular injection of ceftriaxone 500 mg. Doxycycline (100 mg twice daily for 7 days) is added if there is a possibility of co-infection with chlamydia. If ceftriaxone is difficult to use, spectinomycin 2 g can be injected intramuscularly in Korea. Patients with gonorrhea should have repeated examinations within three months at the exposure site because of a high risk of re-infection. A person diagnosed with gonorrhea should discuss the nature of the infection, the importance of informing partners, when sexual activity can resume, and how to reduce the risk of sexually transmitted infections.

Role of microbiome and its metabolite, short chain fatty acid in prostate cancer.

The microbiome which is an assembly of all microbes living inside our bodies performs a major role in maintaining human health and wellness. It has been found that the imbalance of the microbiome can cause various diseases in humans. Similarly, there is growing evidence that the microbiome largely affects a person's chance of contracting certain cancers and how the disease develops and progresses. Studies have shown that about 15% to 20% of all cancers are caused by microbial pathogens. The prevalence of prostate cancer, which is increasing rapidly in Korea, is related to lifestyle including diet. These diets can alter the gut microbial composition, and the effect of the microbiome on prostate cancer development can be estimated. However, the microbiome associated with prostate cancer has been reported differently according to race. This means that the metabolite rather than the specific microbiome will be important. Short chain fatty acids, metabolites of the microbiome, plays an important role in the action mechanism of the microbiome. Short chain fatty acids play roles such as immunomodulation and inhibition of histone deacetylase. Here, we examined the most up-to-date literature featuring the effects of the microbiome on the risk and pathogenesis of prostate cancer.

Differentially Expressed mRNA in Streptozotocin-Induced Diabetic Bladder Using RNA Sequencing Analysis.

PURPOSE: To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. METHODS: An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. RESULTS: The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. CONCLUSION: Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

Decreased Angiopoietin Expression in Underactive Bladder Induced by Long-term Bladder Outlet Obstruction.

PURPOSE: Ischemia of the bladder can occur if neovascular formation cannot keep pace with hypoxia induced by chronic bladder outlet obstruction (BOO). The aim of this study was to examine changes in angiogenesis growth factor expression generated by chronic BOO in a rat model of underactive bladder. METHODS: Twenty female Sprague-Dawley rats aged 6 weeks were assigned to 4 groups (5 rats per group). Group 1 was the control. Group 2 underwent sham surgery. The rats in groups 3 and 4 underwent BOO and were followed up for 1 week and 8 weeks. Cystometry was carried out together with bladder tissue analysis at 1 week and 8 weeks postoperatively. Real-time polymerase chain reaction (PCR) assays were conducted to determine the expression level of angiogenesis-related growth factors. A hypoxia signaling pathway PCR array was additionally carried out. RESULTS: The group that underwent BOO for 8 weeks showed abnormal bladder function, with a diminished intercontraction interval, decreased maximal voiding pressure, and higher volume of residual urine (P<0.05). Hypoxia-inducible factor-1 alpha expression was elevated in this group. The expression levels of vascular endothelial growth factor (VEGF) and VEGF receptor messenger RNA (mRNA) in the BOO group were comparable to those in the control group. However, angiotensin/tie receptor mRNA expression levels increased at 1 week after BOO, but decreased at 8 weeks after BOO. In animals that underwent BOO, fewer blood vessels exhibited positive immunofluorescent staining for von Willebrand factor. Alterations were also seen in the hypoxia signaling pathway PCR array. CONCLUSION: In a rat model of underactive bladder caused by surgical BOO, reduced angiopoietin expression was demonstrated. This observation might underlie visceral ischemia and fibrosis associated with the procedure. The findings of this study might offer an improved understanding of the disease processes underlying BOO and facilitate selection of the appropriate time to repair the organ in this condition.

Differential Gene Expression in the Penile Cavernosum of Streptozotocin-Induced Diabetic Rats.

PURPOSE: Men with diabetes mellitus (DM) often present with severe erectile dysfunction (ED). This ED is less responsive to current pharmacological therapies. If we know the upregulated or downregulated genes of diabetic ED, we can inhibit or enhance the expression of such genes through RNA or gene overexpression. METHODS: To investigate gene changes associated with ED in type 1 DM, we examined the alterations of gene expression in the cavernosum of streptozotocin-induced diabetic rats. Specifically, we considered 11,636 genes (9,623 upregulated and 2,013 downregulated) to be differentially expressed in the diabetic rat cavernosum group (n=4) compared to the control group (n=4). The analysis of differentially expressed genes using the gene ontology (GO) classification indicated that the following were enriched: downregulated genes such as cell cycle, extracellular matrix, glycosylphosphatidylinositol-anchor biosynthesis and upregulated genes such as calcium signaling, neurotrophin signaling, apoptosis, arginine and proline metabolism, gap junction, transforming growth factor-ß signaling, tight junction, vascular smooth muscle contraction, and vascular endothelial growth factor (VEGF) signaling. We examined a more than 2-fold upregulated or downregulated change in expression, using real time polymerase chain reaction. Analysis of differentially expressed genes, using the GO classification, indicated the enrichment. RESULTS: Of the 41,105 genes initially considered, statistical filtering of the array analysis showed 9,623 upregulated genes and 2,013 downregulated genes with at least 2-fold changes in expression (P<0.05). With Bonferroni correction, SLC2A9 (solute carrier family 2 member 9), LRRC20 (leucine rick repeat containing 20), PLK1 (polo like kinase 1), and AATK (apoptosis-associated tyrosine kinase) were all 2-fold changed genes. CONCLUSION: This study broadens the scope of candidate genes that may be relevant to the pathophysiology of diabetic ED. In particular, their enhancement or inhibition could represent a novel treatment for diabetic ED.

The Effect of Testosterone Replacement on Sexual Function in the Elderly: A Systematic Review and Meta-Analysis.

PURPOSE: Healthy aging is an important concern in an aging society. Although the causal relationship between hypogonadism and erectile dysfunction in elderly men remains unclear, many physicians have achieved positive results after implementing exogenous testosterone supplementation therapy in patients with normal or slightly low blood testosterone. The purpose of this study was to conduct a systematic review and meta-analysis on whether testosterone replacement therapy (TRT) could improve sexual function in the elderly, as reported recently. MATERIALS AND METHODS: As a comprehensive literature search was performed to find articles published in PubMed, Embase, and Cochrane databases by January 2022. The search used keywords of 'aged', 'male', 'sexual behavior', and 'testosterone'. Randomized controlled trials (RCTs) were finally selected. As the main effect variable, results of a questionnaire on sexual function were analyzed and the effects of TRT were compared to those of placebo control. RESULTS: Five RCT studies were included in this meta-analysis. The overall improvement by mean difference of sexual function for testosterone supplementation was 0.082 (95% CI: -0.049 to 0.213). In subgroup analysis, only intramuscular injection of 1,000 mg testosterone significantly improved sexual function of the elderly (0.229, 95% CI: 0.112 to 0.347). There was no significant difference in sexual function according to testosterone dose in meta-ANOVA (p=0.957). The difference was not statistically significant either in the meta-regression test (p=0.310). Egger's regression coefficient test did not indicate a publication bias (p=0.132). CONCLUSIONS: Although our overall effect size (that is, sexual function effect of TRT) did not show a significant improvement, the direction of improvement in erection and motivation was clearly shown. The injection formulation resulted in a significant sexual function improvement. Since only a few RCTs were included in the analysis, more well-designed prospective studies are needed to have a definite conclusion.

The correlation between the expression of ubiquitin-conjugating enzyme 2C and prostate cancer prognosis.

PURPOSE: Ubiquitin-conjugating enzyme E2 C (UBE2C) is known to show a causal relationship with cancer development and advancement. The role of UBE2C is to control the mitotic spindle checkpoint. Excess UBE2C has been identified in patients with advanced prostate cancer. The objective of the present study was to examine positive connections between the expression of UBE2C and prognostic factors for prostate cancer. METHODS: Prostate cancer patients' clinical data were analysed. Tissue microarrays (TMAs) were also performed for human prostate cancer tissues (n = 335) and adjacent non-neoplastic tissues (n = 22). TMA slides were incubated with antibodies against UBE2C. Cores were scored by a pathologist who was blind to cancer results. RESULTS: Of 335 prostate cancer patients, 200 could be assessed for biochemical recurrence, clinical recurrence, and overall survival. Human prostate cancer tissues showed higher expression of UBE2C than adjacent non-neoplastic tissues. High expression level of UBE2C showed a strong positive relationship with a high prostate-specific antigen (PSA), Gleason's score, and pathological stage of prostate cancer. Patients with a higher UBE2C grade demonstrated greater lymphatic engagement of prostate cancer than those with a lower UBE2C grade. CONCLUSION: The expression of UBE2C has positive correlations with several prognostic factors for prostate cancer. Thus, investigating the expression level of UBE2C staining is a promising tool for predicting prostate cancer prognosis.

The Correlations between the Intensity of Histopathological Ubiquitin-Specific Protease 11 Staining and Progression of Prostate Cancer.

BACKGROUND: Ubiquitin-specific protease 11 (USP11), one of the principal phosphatase and tensin homolog (PTEN) deubiquitinases, can reserve PTEN polyubiquitination to maintain PTEN protein integrity and inhibit PI3K/AKT pathway activation. The aim of the current study was to investigate the associations between immunohistochemical USP11 staining intensities and prognostic indicators in individuals with prostate cancer. METHODS: Tissue microarrays (TMAs) were performed for human prostate cancer and normal tissue (control) samples. Data on patient's age, Gleason score, plasma prostate-specific antigen (PSA) titer, disease stage, and presence of seminal vesicles, lymph nodes, and surgical margin involvement were collected. A pathologist who was blinded to the clinical outcome data scored the TMA for USP11 staining intensity as either positive or negative. RESULTS: Cancerous tissues exhibited lower USP11 staining intensity, whereas the neighboring benign peri-tumoral tissues showed higher USP11 staining intensity. The degree of USP11 staining intensity was lower in patients with a higher PSA titer, higher Gleason score, or more advanced disease stage. Patients who showed positive USP11 staining were more likely to have more optimal clinical and biochemical recurrence-free survival statistics. CONCLUSIONS: USP11 staining intensity in patients with prostate cancer is negatively associated with several prognostic factors such as an elevated PSA titer and a high Gleason score. It also reflects both biochemical and clinical recurrence-free survival in such patients. Thus, USP11 staining is a valuable prognostic factor in patients with prostate cancer.

Extralobar pulmonary sequestration mimicking an adrenal tumor.

Pulmonary sequestration is a rare cystic malformation composed of bronchopulmonary tissue that is discontinuous from the tracheobronchial tree and has an anomalous systemic blood supply. We present a case of a 40-year old male who presented with an extralobar pulmonary sequestration and underwent a laparoscopic retroperitoneal mass excision. Preoperative imaging revealed a large 11.3-cm retroperitoneal tumor consisting of a multiloculated cystic lesion. The patient was discharged home, and at 3-mo follow-up no complaints were reported.

The Urinary Microbiome; Axis Crosstalk and Short-Chain Fatty Acid.

Our knowledge that "urine is sterile" is no longer accepted after the development of a next-generation sequencing (NGS) test. Using NGS, microbiota in the human body were discovered, and it is expected that this will improve our understanding of human diseases. However, the mechanism involved in the effect of the microbiome on diseases is still poorly understood. Associations of gut microbiome with diseases have been recently reported. Based on such associations, bladder-gut-brain axis, gut-bladder axis, gut-vagina-bladder axis, and gut-kidney axis as novel mechanisms of action of the microbiome have been suggested. Each axis can influence the development and progression of disease through interactions. In these interactions, metabolites of the microbiome including short-chain fatty acids (SCFA) and the inflammasome play an important role. Inflammasomes are multiprotein oligomers that can initiate inflammatory responses. Inflammasomes can trigger inflammation and pyroptosis and ultimately contribute to disease development. SCFAs play an important role in immune cell migration, cytokine production, and maintenance of cellular homeostasis. Associations of inflammasomes with systemic diseases such as obesity and insulin resistance have been reported. The roles of inflammasomes and SCFAs in kidney, bladder, and prostate diseases have also been revealed recently.

Changes of proapoptotic and antiapoptotic genes affect sensitivity to apoptotic stimuli in impaired contractility due to long term bladder outlet obstruction.

INTRODUCTION: The normal biological process that necessitates cell removal greatly depends on apoptosis. Long term bladder outlet obstruction (BOO) causes damaged smooth muscle cells to undergo apoptosis. However, smooth muscle cell apoptosis that BOO causes is not well known in impaired bladder contractility. Therefore, we designed this study to investigate whether long-term BOO could induce apoptosis activities and to obtain an expression profile of apoptosis related genes. MATERIALS AND METHODS: We used 10 Sprague-Dawley six-week-old female rats. We separated them equally into two groups: a sham intervention group (group 1) and an eight-week BOO group (group 2). We conducted cystometric evaluation eight weeks following BOO onset, with processing of bladder tissue for PCR array. Every array comprised 84 genes, which were established to contribute to an apoptosis response, cell differentiation and metabolism, and 12 sequences were established for the regulation of loading and the quality of cDNA. We performed real-time PCR. Changes in gene expression presented as a fold increase/decrease. Alterations of more than two-fold constituted the cut-off determining expression. RESULTS: Group 2 had a greater bladder weight and Impaired bladder contractility. Immunofluorescent staining with CAS3, TUNEL showed increased in the BOO group. In comparison to group 1, group 2 exhibited an at least two-fold upregulation in five genes, the Bcl-2 (15.1), Birc5 (5.8), Cd40lg (7.5), Il10 (16.2), and Naip2 (13.2). They also demonstrated at least a two-fold downregulation in the PRLR (-18.1) gene. Genes Bcl2ald, Circ5, Cd40lg, Il10, Naip2, and PRLR were among the genes with activity against apoptosis. TNF, STAT3 and TP53 mediated the effect that genes had on one another. CONCLUSION: This study demonstrated that the relative ratios of pro- and antiapoptotic genes determine bladder cell sensitivity cells to apoptotic stimuli in impaired contractility caused by long term BOO. Although we cannot confirm whether this finding is the result of the decompensated phase of the bladder or the process, the gene expression profiles could explain molecular mechanisms of apoptosis in impaired bladder contractility caused by long-term BOO with further studies.

Improvement of erectile dysfunction using endothelial progenitor cells from fetal cerebral vasculature in the cavernous nerve injury of rats.

BACKGROUND: Because of limited differentiation to endothelium from mesenchymal stem cells, it has been strongly recommended to use endothelial progenitor cells for the regeneration of the damaged endothelium of corpora cavernosa. This study was performed to investigate the immortalized human cerebral endothelial cells and their capability for repairing erectile dysfunction in a rat model of cavernous nerve injury. Circulating endothelial progenitor cells were isolated from human fetal brain vasculature at the periventricular region of telencephalic tissues. Over 95% of CD 31-positive cells were sorted and cultured for 10 days. Human cerebral endothelial progenitor cells were injected into the cavernosa of rats with cavernous nerve injury. Erectile response was then assessed. In in vivo assays, rats were divided into three groups: group 1, sham operation: group 2, bilateral cavernous nerve injury: and group 3, treatment with human cerebral endothelial cells after cavernous nerve injury. RESULTS: Established immortalized circulating endothelial progenitor cells showed expression of human telomerase reverse transcriptase transcript by RT-PCR. They also showed the expression of vascular endothelial growth factor, von Willebrand factor, vascular endothelial growth factor receptor, and CD31, cell type-specific markers for endothelial cells by RT-PCR. In in vitro angiogenesis assays, they demonstrated tube formation that suggested morphological properties of endothelial progenitor cells. In in vivo assays, impaired erectile function of rat with cavernous nerve injury recovered at 2, 4, and 12 weeks after transplantation of human cerebral endothelial cells into the cavernosa. CONCLUSIONS: Telomerase reverse transcriptase-circulating endothelial progenitor cells from fetal brain vasculature could repair erectile dysfunction of rats with cavernous nerve injury.

RéSUMé: CONTEXTE: En raison de la différenciation limitée de l'endothélium à partir de cellules souches mésenchymateuses, il a été fortement recommandé d'utiliser des cellules progénitrices endothéliales pour la régénération de l'endothélium endommagé des corps caverneux. Cette étude a été réalisée pour étudier les cellules endothéliales cérébrales humaines immortalisées, et leur capacité à réparer la dysfonction érectile dans un modèle de rat avec lésion du nerf caverneux. Les cellules progénitrices endothéliales circulantes ont été isolées du système vasculaire cérébral fœtal humain dans la région périventriculaire des tissus télencéphaliques. Plus de 95% des cellules CD31 positives ont été sélectionnées et cultivées pendant 10 jours. Des cellules progénitrices endothéliales cérébrales humaines ont été injectées dans les corps caverneux de rats présentant une lésion nerveuse des corps caverneux. La réponse érectile a ensuite été évaluée. Dans les essais in vivo, les rats ont été divisés en trois groupes: groupe 1, opération simulée; groupe 2, lésion bilatérale du nerf caverneux; et groupe 3, traitement par cellules endothéliales cérébrales humaines après lésion du nerf caverneux. RéSULTATS: Les cellules progénitrices endothéliales circulantes immortalisées établies ont montré l'expression de la transcription de la transcriptase inverse de la télomérase humaine par RT-PCR. Elles ont également montré l'expression du facteur de croissance de l'endothélium vasculaire, du facteur de von Willebrand, du récepteur du facteur de croissance de l'endothélium vasculaire, et de CD31, marqueurs spécifiques du type cellulaire par RT-PCR pour les cellules endothéliales. Dans les essais in vivo, la fonction érectile altérée des rats avec lésion du nerf caverneux s'est rétablie à 2, 4 et 12 semaines après transplantation de cellules endothéliales cérébrales humaines dans les corps caverneux. CONCLUSIONS: Les cellules progénitrices endothéliales circulantes exprimant la transcriptase inverse de la télomérase, provenant du système vasculaire cérébral fœtal humain, pourraient réparer la dysfonction érectile de rats atteints de lésions des nerfs caverneux. MOTS-CLéS: Dysfonction érectile; Cellules endothéliales humaines; Transcriptase inverse de la Télomérase humaine.

Penile schwannoma mistaken for hemangioma: a rare case report and literature review.

Penile neoplasm is uncommon. Schwannomas of the penis are especially rare. For this reason, it is difficult to get an accurate impression to enable decision making. This report primarily deals with the mistaken diagnosis of hemangioma, to the surgery, and the follow-up in real-world. A 38-year-old male patient presented with a palpable mass in the penile root that increased in size with erection. One year after the mass had been found, the patient visited the hospital and complained that the mass was growing. Moreover, the patient explained that the mass seemed to increase during penile erection. On physical examinations, a 2 cm mass without tenderness was palpated in the left penoscrotal junction. About 2.1 cm in size, an isoechoic mass was observed next to the corpus cavernosum on ultrasonography. There was high vascularity inside of the mass. Excision and biopsy were decided upon. Following surgery, a schwannoma was confirmed by pathology. After three months, the patient did not complain of any symptoms and had normal erectile function. Most of these tumors are benign. By December 2020, 40 cases were reported, of which 6 were diagnosed as malignant. The most frequent occurrence site is the penile shaft. In all cases, surgical resection was performed and no recurrence was found. The aim of this case report is to assist clinicians in choosing the best treatment option when faced with this rare condition by discussing the radiological, pathological, and clinical course.

Improved bladder contractility after transplantation of human mesenchymal stem cells overexpressing hepatocyte growth factor into underactive bladder from bladder outlet obstruction models of rats.

INTRODUCTION: An underactive bladder can lead to difficulty in voiding that causes incomplete emptying of the bladder, suggesting the need for a new strategy to increase bladder contractility in such patients. This study was performed to investigate whether human mesenchymal stem cells (hMSCs) were capable of restoring bladder contractility in rats with underactive bladder due to bladder outlet obstruction (BOO) and enhancing their effects by overexpressing hepatocyte growth factor (HGF) in hMSCs. MATERIALS AND METHODS: The hMSCs were transplanted into the bladder wall of rats. Fifty female Sprague-Dawley rats at six weeks of age were divided into five groups: group 1: control; group 2: sham intervention; group 3: eight-week BOO; group 4: BOO rats transplanted with hMSCs; and group 5: BOO rats transplanted with hMSCs overexpressing HGF. Two weeks after the onset of BOO in groups 4 and 5, hMSCs were injected into the bladder wall. Cystometry evaluation was followed by Masson's trichrome staining of bladder tissues. Realtime PCR and immunohistochemical staining were performed to determine for hypoxia, apoptosis, and angiogenesis. RESULTS: Collagen deposition of bladder increased in BOO but decreased after transplantation of hMSCs. The increased inter-contraction interval and residual urine volume after BOO was reversed after hMSCs transplantation. The decreased maximal voiding pressure after BOO was restored by hMSCs treatment. The mRNA expression of bladder collagen1 and TGF-ß1 increased in BOO but decreased after hMSCs transplantation. The decrease in vWF-positive cells in the bladder following BOO was increased after hMSCs transplantation. Caspase 3 and TUNEL-positive apoptosis of bladder cells increased in BOO but decreased after transplantation of hMSCs. These effects were enhanced by overexpressing HGF in hMSCs. CONCLUSION: Transplantation of hMSCs into bladder wall increased the number of micro-vessels, decreased collagen deposition and apoptosis of detrusor muscle, and improved bladder underactivity. The effects were enhanced by overexpressing HGF in hMSCs. Our findings suggest that the restoration of underactive bladder using hMSCs may be used to rectify micturition disorders in patients following resolution of BOO. Further studies are needed before hMSCs can be used in clinical applications.

Accelerating neovascularization and kidney tissue formation with a 3D vascular scaffold capturing native vascular structure.

Establishing an adequate vascularization of three-dimensional (3D) bioengineered tissues remains a critical challenge. We previously fabricated a vascular scaffold using the vascular corrosion casting technique, which provides a similar 3D geometry of native kidney vasculature. In this study, we functionalized the collagen vascular scaffold with a controlled release of vascular endothelial growth factor (VEGF vascular scaffold) to further promote vascularization. The VEGF vascular scaffold showed improved angiogenic capability in 2-dimensional (2D) and 3D in vitro settings. Implantation of the VEGF vascular scaffold seeded with human renal cells into a rat kidney demonstrated enhanced implant vascularization and reduced apoptosis of implanted human renal cells. Hybrid renal tubule-like structures composed of implanted human and migrated host renal cells were formed. This work highlights the critical role of early vascularization of the geometrically mimetic vascular scaffold using the VEGF incorporated vascular scaffold in reducing apoptosis of implanted cells as well as the formation of renal tissue structures.