Background Mesenchymal stem cell therapy (MSCT) and defocused low-energy shock wave therapy (ESWT) has been shown to ameliorate erectile dysfunction (ED). However, the interactions and effects of action between MSCT and ESWT remain poorly understood. In this study, we investigated the mechanisms of combination therapy with MSCT and ESWT in a rat model of diabetic ED. Materials and Methods Eight-week-old male Sprague-Dawley rats were randomly divided into 2 parts. Diabetic rats induced by streptozotocin (65 mg/kg) were randomly divided into 4 groups: (1) DM control group, (2) DM + ESWT group, (3) DM + MSCT group, and (4) DM + ESWT + MSCT group. The sham group was a normal control group (without streptozotocin). MSCT and (or) ESWT were, respectively, administered to each group according to the proposal for 8 weeks. Immediately after recording of intracavernous pressure (ICP), the penis was then harvested for histologic analysis, ELISA, and Western blotting. Results The ratio of ICP/MAP was significantly higher in the DM + ESWT + MSCT group than in ESWT or MSCT treated group (P < 0.05). Also, the treatment stimulated angiogenesis and vasodilatation in the corpus cavernosum (P < 0.05). ESWT increased the quantity of MSCs in the corpus cavernosum and also induced MSCs to express more VEGF in vitro and vivo (P < 0.05) which activated the PI3K/AKT/mTOR and NO/cGMP signaling pathways in the corpus cavernosum. The combination approach stimulated autophagy and decreased apoptosis in the corpus cavernosum. NGF and BDNF expressions were higher in the DM + ESWT + MSCT group than in the DM control group (P < 0.01). Furthermore, the treatment promoted the MSC recruitment by inducing penile tissues to express more PECAM and SDF-1. Conclusions Combination of LI-ESWT and MSCT can get a better result than a single treatment by expressing more VEGF which can take part in autophagy by triggering the PI3K/AKT/mTOR signaling pathway. This cooperative therapy would provide a new research direction in ED treatment for the future.

Effective therapies for erectile dysfunction (ED) associated with diabetes mellitus (DM) are needed. In this study, the effects of stromal cell-derived factor-1 (SDF-1)-expressing engineered mesenchymal stem cells (SDF-1 eMSCs) and the relevant mechanisms in the corpus cavernosum of a streptozotocin (STZ)-induced DM ED rat model were evaluated. In a randomized controlled trial, Sprague–Dawley (SD) rats (n = 48) were divided into four groups (n = 12/group): Normal (control), DM ED (diabetes induced by STZ), DM ED + BM-MSC (treated with bone marrow [BM]-derived MSCs), and DM ED + SDF-1 eMSC (treated with SDF-1-expressing BM-MSCs). After four weeks, intracavernosal pressure (ICP), an indicator of erectile function, was 0.75 ± 0.07 in the normal group, 0.27 ± 0.08 in the DM ED group, 0.42 ± 0.11 in the DM ED + BM-MSC group, and 0.58 ± 0.11 in the DM ED + SDF-1 eMSC group. BM-MSCs, especially SDF-1 eMSCs, improved ED (p < 0.05). SDF-1 eMSC treatment improved the smooth muscle content in the corpus cavernosum (p < 0.05). As SDF-1 expression increased, ED recovery improved. In the SDF-1 eMSC group, levels of neuronal nitric oxide synthase (nNOS) and phosphorylated endothelial NOS (p-eNOS) were higher than those in other groups (p < 0.05). In addition, high stromal cell-derived factor-1 (SDF-1) expression was associated with increased vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in DM ED rats (p < 0.05). Higher levels of phosphorylated protein kinase B (p-AKT)/protein kinase B (AKT) (p < 0.05) and B-cell lymphoma-2 (Bcl-2) and lower levels of the apoptosis factors Bcl2-associated x (Bax) and caspase-3 were observed in the MSC-treated group than in the DM ED group (p < 0.05). SDF-1 eMSCs showed beneficial effects on recovery from erectile function.

Introduction There are only a few studies on the clinical utility of filler injections for penile augmentation (PA) in patients with small penis syndrome (SPS), which is a type of anxiety or body dysmorphic disorder, not a true micropenis. Aim To compare the clinical outcomes of hyaluronic acid (HA) with polylactic acid (PLA) filler injection for temporary PA in patients with SPS. Methods Our prospective, patient/evaluator-blind, comparative, randomized, non-inferiority trial consisted of a single filler injection and a 24-week post-injection period. Seventy-four men with SPS were included between November 2017 and February 2018. Patients were divided into those injected with HA (n = 39) and those injected with PLA filler (n = 35). Main Outcome Measure The psychological effects of PA, based on the Beliefs about Penis Size Scale, penile girth, and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks post-injection. Results At 24 weeks, the mean penile girth increases were 2.1 ± 1.0 cm (P &lt; .001) in the HA group and 1.6 ± 0.9 cm (P &lt; .001) in the PLA group, with a mean difference of 0.5 ± 0.2 cm between groups (P = .031). In both groups, satisfaction levels significantly increased at 24 weeks, with 1.8 ± 1.7 and 1.6 ± 1.4 mean increases in the visual analog scale for penile appearance satisfaction in the HA and PLA groups, respectively (each P &lt; .001), and 1.0 ± 1.1 and 0.7 ± 1.2 mean increases in the visual analog scale for sexual life satisfaction in the HA and PLA groups, respectively (each P &lt; .001), with no significant differences between groups (P = .950 and P = .287). The mean Beliefs about Penis Size Scale scores significantly decreased at 24 weeks, with 7.8 ± 8.3 and 5.3 ± 7.2 mean decreases in the HA and PLA groups, respectively (each P &lt; .001), and no significant difference between the groups (P = .920). There were no serious adverse events, but filler injection-related adverse events in the HA and the PLA groups were reported in 2 cases (5.13%) and 5 cases (14.29%), respectively (P = .245). Clinical Implications Our study provides an overview of clinical course after HA and PLA filler injections for PA and suggests that filler injections can be considered an alternative approach in patients with SPS. Strengths & Limitations Our study is the first to assess the psychological symptoms in patients with SPS who received the filler injection for PA; however, the follow-up duration was insufficient to prove the long-term outcomes of fillers. Conclusion Without serious adverse events, HA and PLA filler injections for PA significantly resulted in not only an augmentative effect but also improvement of psychological distress, and the clinical utility was comparable between the fillers.

Desmopressin add-on therapy for refractory nocturia in men previously treated with an α-blocker for lower urinary tract symptoms improved voiding symptoms as well as nocturia, storage symptoms.

Background This study aims to evaluate the effect of extracorporeal shock wave therapy (ESWT) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to explore the mechanism. Methods RWPE‐2 cells were randomly divided into three groups: (a) RWPE‐2 group (normal control), (b) LPS groups (lipopolysaccharide inducing inflammation) and (c) ESWT groups (LPS induced RWPE‐2 treated by ESWT). After ESWT was administered, cells and supernatant were collected for enzyme‐linked immunosorbent assay (ELISA) and Western blot analysis. In vivo, Sprague‐Dawley rats (n = 30) were randomly divided into three groups: (a) normal control group, (b) prostatitis groups, and (c) ESWT groups. Prostatitis rats were induced by 17 β‐estradiol and dihydrotestosterone for 4 weeks. After ESWT, prostates of each group were collected for immunohistochemistry, Western blot analysis, and ELISA. Results ESWT improved prostatitis by attenuating inflammation (P < .01). ESWT downregulated the expression of cyclooxygenase 2 (COX‐2) through inhibiting TLR4‐NFκB pathway compared with the LPS group in vitro or prostatitis group in vivo (P < .05). TRAF2 mediates ERK1/2‐COX2 pathway. ESWT promotes prostate tissue recovery by stimulating vascular endothelial growth factor expression (P < .01). ESWT could suppress apoptosis in the prostate. Conclusions ESWT improved CP/CPPS and reduced inflammation by degrading COX‐2 in microenvironment through TLR4‐NFκB‐inhibiting pathway. TRAF2 regulator in ERK1/2‐COX‐2 inhibition significantly reduced inflammation, thus suggesting ESWT may be a potential and promising treatment for CP/CPPS.

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

Purpose: We examined the association between obesity and prostate cancer both with and without diabetic patients included in the analysis using nationally representative data of the Korean population from the National Health Insurance System (NHIS).Materials and Methods: Of the 424,712 participants who underwent health examinations in 2002-2008, 139,519 men ≥40 years old and without prostate cancer were followed from the beginning of 2002 to the end of 2012. Multivariate adjusted Cox regression analysis was conducted to examine the hazard ratio (HR) and 95% confidence interval (CI) for the association between prostate cancer and body mass index (BMI) both with and without diabetes.Results: The HR for prostate cancer according to the existence of diabetes was stratified by BMI in both age- and multivariable-adjusted models. In the population without diabetes, the HR for prostate cancer significantly increased as BMI increased beyond the reference range in a model adjusted for age and multiple variables; however, the increase in the HR was small. In the population with diabetes, the HR for prostate cancer significantly increased as BMI increased from < 18.5 kg/m2 to within the reference range (18.5 to 22.9) in the multivariable-adjusted model. In addition, a marked decrease in HR in the population with BMI of < 18.5 kg/m2 was seen compared to the reference or higher BMI population.Conclusion: This population-based study shows the evidence of association between obesity and development of prostate cancer, and the risk increases vary according to the change of BMI category and the existence of diabetes.

PurposeMale infertility is a serious problem, and its prevalence has been increasing. Therefore, we investigated the safety of a new herbal formula and its effects on sperm quality.Materials and MethodsAn in vitro cytotoxicity test in TM3 Leydig cells was performed to evaluate cell viability after administration of five types of herbs separately and of a new herbal formula containing these five. An in vivo test in male mice was performed to evaluate the influence of the new herbal formula on the reproductive organs and sperm quality. After the 8- and 28-day oral administration of the new herbal formula, the weights of the reproductive organs were measured and the sperm count and motility were evaluated.ResultsIn the in vitro cytotoxicity test, less than 80% cell viability at concentrations of 500 mg/L and 1,000 mg/L of Rubus coreanus Miquel and Cuscuta chinensis Lam was observed. However, more than 80% cell viability was observed at all the tested concentrations of the new herbal formula. After the 8- and 28-day oral administration, there were no considerable changes in body weight. The weights of the testes, epididymis, and seminal vesicles after the 8- and 28-day oral administration were similar to those of the control. The sperm count and activity were significantly improved compared with those of the control group at 8 and 28 days after 100, 200, and 400 mg of oral administration.ConclusionsThe safety of the new formula and its positive effect on the sperm quality were observed after the oral administration of the formula.