Quisqualis indica extract for men with lower urinary tract symptoms: A randomized, double-blind, placebo-controlled trial.

PURPOSE: To evaluate the efficacy and safety of Quisqualis indica in men with moderate lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: A total of 135 subjects with International Prostate Symptom Score (IPSS) of 8-19 were randomized in 2 centers from June 2018 to April 2019. Patients were assigned into one of the three groups: a low-dose group (LG, 1,000 mg Q. indica), a high-dose group (HG, 2,000 mg Q. indica) or a placebo group (PG). The primary endpoint was the change of IPSS at the end of treatment from baseline. Secondary end points included the changes of prostate specific antigen, testosterone, dihydrotestosterone, maximum urinary flow rate (Qmax), postvoid residual volume (PVR) and International Index of Erectile Function-5 (IIEF-5), with drug safety. RESULTS: 113 patients were able to finish the study. Compared to the PG, total IPSS in the LG and the HG was significantly improved at 6 weeks and 12 weeks. For IPSS subscores, LG showed improvements in all except for urgency and quality of life at 6 weeks. HG showed improvements in incomplete emptying and frequency at 6 weeks and 12 weeks along with improvements in intermittency, straining, and quality of life at 12 weeks. For IIEF-5 subscores, orgasmic function and overall satisfaction improved in HG when compared to PG at 12 weeks. Lastly, increase of Qmax and decrease of PVR was observed at 6 weeks in LG. CONCLUSIONS: 12-week treatment with Q. indica has a therapeutic effect and is well tolerated in patients with LUTS.

Efficacy and Safety of Maca (Lepidium meyenii) in Patients with Symptoms of Late-Onset Hypogonadism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

PURPOSE: To evaluated the efficacy and safety of gelatinized Maca (Lepidium meyenii) for eugonadal patients with late onset hypogonadism symptoms (LOH). MATERIALS AND METHODS: Participants were instructed to receive 1,000 mg of Maca or placebo, two pills at a time, three times per day for 12 weeks before food intake. To evaluate the efficacy of the drug, Aging Males' Symptoms scale (AMS), Androgen Deficiency in the Aging Males (ADAM), International Prostate Symptom Score (IPSS), and International Index of Erectile Function (IIEF) questionnaires, serologic tests (total testosterone and free testosterone, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride), body weight, and waist circumference were assessed at 4 and 12 weeks after treatment. RESULTS: A total of 80 participants were enrolled and randomly assigned to Maca treated group (n=41) or the placebo group (n=39). AMS, IIEF, and IPSS were significantly (p<0.05) improved in Maca treated group than in the placebo group. ADAM positive rate was also significantly (p<0.0001) decreased in Maca treated group. CONCLUSIONS: Maca may be considered an effective and safe treatment for eugonadal patients with late onset hypogonadism symptoms.

Effect of high-BDNF microenvironment stem cells therapy on neurogenic bladder model in rats.

BACKGROUND: The purpose of this study is to explore the effects of high-BDNF microenvironment produced by engineered immortalized mesenchymal stem cells (imMSCs) on the neurogenic bladder (NB) and investigate underlying mechanism. METHODS: Male Sprague-Dawley rat (12-week-old, weighing about 370-400 g) were purchased from a Korean company (Orient Bio Co. Seongnam, Korea) and divided into the following groups (n=32): sham control group (n=8), NB group (n=8), NB + ImMSCs group (n=8), NB + ImMSCs (BDNF) group (n=8). The major pelvic ganglion (MPG) was observed under anesthesia. Three NB groups of rats were then subjected to bilateral MPG injury. The sham control group of rats was treated with sham surgery. Cystometry were performed before the rats were sacrificed, and then MPG and bladder were collected for histochemical and Western blot analysis. RESULTS: MSCs treatment improves lower urinary tract function, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). MSCs treatment accelerates recovery of injured nerve tissue, and the NB + ImMSCs (BDNF) group is better than the NB + ImMSCs group (P<0.01). In high BDNF environment, apoptosis was reduced more significantly and muscle tissue recovered more rapidly (P<0.01). High-BDNF microenvironment activates more BDNF/TrkB/CREB signaling pathways (P<0.01). CONCLUSIONS: In a rat NB model caused by nerve injury, imMSCs have certain effects on nerve tissue repair. At the same time, it was proved that increasing the expression of BDNF which had specific effect on nerve injury repair could more effectively repair injured MPG in local microenvironment. The mechanism may be related to the activation of the BDNF/TrkB/CREB signaling pathway and the reduction of apoptosis by highly expressed BDNF.

Combined treatment with extracorporeal shockwaves therapy and an herbal formulation for activation of penile progenitor cells and antioxidant activity in diabetic erectile dysfunction.

BACKGROUND: A Korean herbal formulation named KH-204 was reported to have an antioxidant effect in our previous study. We hypothesized that Low-intensity extracorporeal shockwave therapy (Li-ESWT) combined with KH-204 would accelerate the treatment of erectile dysfunction (ED) by enhancing antioxidant. We investigated the synergistic effect of Li-ESWT and KH-204 for ED and explored the mechanism. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with KH-204 and LI-ESWT in vitro. Fifty 5-week-old male Sprague Dawley rats received an intraperitoneal injection of 5-ethynyl-20-deoxyuridine (EdU) which can label live cells, and were randomly divided into five groups: (I) normal; (II) diabetes mellitus-associated erectile dysfunction (DMED); (III) DMED + KH-204; (IV) DMED + Li-ESWT; and (V) DMED + KH-204/Li-ESWT. Li-ESWT treatment was repeated three times a week every other day for four weeks in group 4 and 5. Meanwhile, rats in group 3 and 5 were orally fed 400 mg/kg of KH-204 daily for 1 month. Following a 1-week washout period, penile tissues were evaluated by immunostaining and Western blotting. RESULTS: KH-204 combined with Li-ESWT improved intracavernosal pressure (ICP) in DMED rats. Li-ESWT/KH-204 stimulated HUVEC tube formation and promoted proliferation. Li-ESWT drove progenitor cells to migrate to penile tissue and KH-204 protected penile progenitor cells in the corpus cavernosum. Oxidative stress was relieved by KH-204/Li-ESWT. Treatment with KH-204/Li-ESWT protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. KH-204/Li-ESWT protected penile tissue from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), increasing superoxide dismutase (SOD), decreasing 8-hydroxy-20-deoxyguanosine (8-OHdG), and reducing apoptosis. KH-204/Li-ESWT promoted stromal derived factor-1 (SDF-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in DMED rats. CONCLUSIONS: KH-204 protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. The combination of Li-ESWT and KH-204 as a synergy therapy could be a potential and effective treatment for DMED.

Engineered Stem Cells Improve Neurogenic Bladder by Overexpressing SDF-1 in a Pelvic Nerve Injury Rat Model.

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1+) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1-). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1+, imMSCs/eSDF-1-, or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1+ expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1+ improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1+ group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1+ group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1+ group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

Electric Stimulation Hyperthermia Relieves Inflammation via the Suppressor of Cytokine Signaling 3-Toll Like Receptor 4 Pathway in a Prostatitis Rat Model.

PURPOSE: Chronic prostatitis (CP), including chronic pelvic pain syndrome (CPPS), is the most commonly encountered manifestation of prostatitis. The aim of this study was to evaluate the effect of electric stimulation hyperthermia treatment (ESHT) on CP/CPPS and to explore the underlying mechanism. MATERIALS AND METHODS: RWPE-2 cells with lipopolysaccharide-induced inflammation and a prostatitis rat model induced by 17ß-estradiol and dihydrotestosterone underwent sham, electric stimulation, or ESHT treatment. Four weeks later, cells, supernatants, and rat prostates were collected for analysis using immunohistochemistry, Western blots, and enzyme-linked immunosorbent assays. RESULTS: We found that ESHT improved prostatitis in vivo and attenuated inflammation in vitro. ESHT significantly induced suppressor of cytokine signaling 3 (SOCS3) expression and subsequently promoted HSP70. It attenuated inflammation through decreased expression of toll-like receptor 4 (TLR4), nuclear factor kappa B, and subsequent inflammatory cytokines. ESHT also inhibited apoptosis and released growth factor in tissue affected by prostatitis. CONCLUSIONS: ESHT improved CP/CPPS and reversed pathologic changes of prostatitis by inhibiting the SOCS3-TLR4 pathway.

Mesenchymal Stem Cells Treatment for Erectile Dysfunction in Diabetic Rats.

INTRODUCTION: Aging men with diabetes mellitus are more easily suffering from erectile dysfunction (ED), which was poor to respond to drugs. Mesenchymal stem cell treatment (MSCT) offers us an alternative approach that might reverse diabetes mellitus erectile dysfunction (DMED). AIM: The aim of this study was to review the current studies investigating mesenchymal stem cell approach in diabetic rat models of ED for future research. METHODS: A medical literature search was performed in PubMed by using the keywords including erectile dysfunction, mesenchymal stem cells, diabetes mellitus, and rat model. MAIN OUTCOME MEASURE: Representative studies on DMED rats treated by MSCT were reviewed. RESULTS: Streptozocin-induced type 1 diabetes mellitus rats were used in most studies because of cost and convenience. With the development of stem cell treatment for DMED research, many kinds of stem cells were used in animal experiment, such as bone marrow-derived mesenchymal stem cells, adipose-derived stem cells, human umbilical cord blood mononuclear cells, muscle-derived stem cells, urine-derived stem cells, neural crest stem cells, and endothelial progenitor cells. Although diverse stem cells were applied for DMED treatment, the mechanism behind these approaches was identical, including improving vascular injury, recovering smooth muscle, restoring neuronal cells, inhibiting the generation of inflammatory cytokines, homing mesenchymal stem cells, and decreasing apoptosis in corpus cavernosum. Meanwhile, combination therapies, including MSCT with drug, herb, and low-energy extracorporeal shockwave treatment showed satisfactory results for ED. CONCLUSION: It has been proved that MSCT is an effective and safe treatment for the DMED rats. What's more, MSCT might be a potential and promising approach for patients with DMED as a minimally invasive treatment. Combination of MSCT with various methods was proved to be a more efficient treatment and dependable option to make up for deficiencies of MSCT. Kim SW, Zhu GQ, Bae WJ. Mesenchymal Stem Cells Treatment for Erectile Dysfunction in Diabetic Rats. Sex Med Rev 2020;8:114-121.

Extracorporeal shock wave therapy decreases COX-2 by inhibiting TLR4-NFκB pathway in a prostatitis rat model.

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 ß-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.

Synergistic effects of extracorporeal shockwave therapy and modified Ojayeonjonghwan on erectile dysfunction in an animal model of diabetes.

Purpose: We investigated the synergy effect of extracorporeal shock wave therapy (ESWT) with modified Ojayeonjonghwan (Korean herbal formula, KH-204) in an animal model of diabetes mellitus (DM)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male Sprague-Dawley rats were used in this study. DM was induced by an intraperitoneal injection of streptozotocin. DM rats were divided into 5 groups (n=10 per group): group 1, control; group 2, DM; group 3, DM+ESWT; group 4, DM+KH-204; and group 5, DM+ESWT+KH-204. In ESWT groups, rats were treated with ESWT at the penis 3 times a week for 2 weeks under anesthesia. The KH-204 groups were treated with a daily oral dose of KH-204 for 12 weeks. After all treatments, intracavernosal pressure (ICP) was measured, and the cavernous tissues were evaluated by Masson's trichrome, immunohistochemistry and western blot analysis. Results: ICP was evaluated as a measurement of erectile function. The DM+ESWT, DM+KH-204, and DM+ESWT+KH-204 groups showed significantly restored erectile function compared with the DM group (p<0.05). Among these groups, the DM+ESWT+KH-204 group showed the highest ICP. Moreover, ESWT and KH-204 treatment restored smooth muscle contents and many parameters related to potency (vascular endothelial growth factor, neuronal nitric oxide synthase (NOS), endothelial [NOS] and platelet endothelial cell adhesion molecule-1) compared with the DM group (p<0.05). Conclusions: We confirmed the potential efficacy of ESWT and KH-204 in the treatment of ED patients using an animal model. The combination treatment of KH-204 and ESWT is expected to have good potential clinical results in the future treatment of refractory ED.

Effect of Korean Herbal Formula (Modified Ojayeonjonghwan) on Androgen Receptor Expression in an Aging Rat Model of Late Onset Hypogonadism.

PURPOSE: Testosterone replacement therapy is an effective treatment for late-onset hypogonadism (LOH) despite a few contraindications and side-effects. The aim of this study was to determine whether modified Ojayeonjonghwan (KH-204, Korean herbal formula) improved LOH. KH-204 is a strong antioxidant herbal formula. We evaluated the effect of Korean herbal prescription on androgen receptor (AR) expression in an aged rat model of LOH. MATERIALS AND METHODS: Eighteen-month-old rats were used as aged LOH rat models. Eighteen Sprague-Dawley rats were randomly divided into three equal groups of six animals each and treated with one of the following: 1) normal control group (oral administration with distilled water, n=6), 2) KH-204 200 group (oral administration with 200 mg/kg of KH-204, n=6), and 3) KH-204 400 group (oral administration with 400 mg/kg of KH-204, n=6). After four weeks of treatment (once daily, distilled water or KH-204), serum testosterone levels, changes in testicular and epididymal weight, Western blotting analysis of AR expression and measurement of oxidative stress were examined. RESULTS: Treatment with the herbal formulation KH-204 200 mg/kg and 400 mg/kg (1) increased the weights of testis and epididymis; (2) increased the level of serum testosterone; (3) increased the level of superoxide dismutase and reduced the level of 8-hydroxy-20-deoxyguanosine; and (4) upregulated AR expression in testicular tissue. CONCLUSIONS: KH-204 might be an effective alternative for LOH. It improves antioxidant mechanisms and increases testicular AR expression without side-effects.

Engineered Mesenchymal Stem Cells Expressing Stromal Cell-derived Factor-1 Improve Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

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.

Efficient Promotion of Autophagy and Angiogenesis Using Mesenchymal Stem Cell Therapy Enhanced by the Low-Energy Shock Waves in the Treatment of Erectile Dysfunction.

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.

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway.

The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-ß) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

Effects of Next-Generation Low-Energy Extracorporeal Shockwave Therapy on Erectile Dysfunction in an Animal Model of Diabetes

PURPOSE: Gene therapy, stem cell therapy, and low-energy extracorporeal shockwave therapy (ESWT) have been investigated as treatments for refractory erectile dysfunction (ED), but inconclusive evidence has been obtained. We investigated the effect of a next-generation electromagnetic cylinder ESWT device on an animal model of ED. MATERIALS AND METHODS: Diabetes mellitus (DM)-induced rats were divided into 3 groups: group 1, control; group 2, DM; and group 3, DM+ESWT. Rats were treated with ESWT 3 times a week for 2 weeks. After the treatment course, intracavernous pressure was measured and the corpus cavernosum and cavernous nerve were evaluated. RESULTS: In the DM group, all parameters predicted to be significantly lower in the ED model had statistically significantly decreased (p < 0.01). As a measurement of erectile function, intracavernous pressure was evaluated. The DM+ESWT group exhibited significantly restored erectile function compared to the DM group (p < 0.05). Moreover, ESWT treatment restored smooth muscle content, as assessed by Masson's trichrome staining (p < 0.05). Finally, corporal tissue and the dorsal nerve were evaluated by immunohistochemistry, Western blotting, and ELISA. After ESWT treatment, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), platelet endothelial cell adhesion molecule-1, cyclic guanosine monophosphate, and neuronal nitric oxide synthase (nNOS) expression levels were restored to levels in the DM group (p < 0.05). CONCLUSIONS: Electromagnetic cylinder ESWT device resulted in increased VEGF, nNOS, and eNOS expression; reduced smooth muscle atrophy; and increased endothelial cell regeneration in a DM-associated ED model. Our data suggest that safe and effective application could be possible in future clinical studies.

A bladder cancer microenvironment simulation system based on a microfluidic co-culture model.

A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cells co-cultured simultaneously. This simulation system comprises perfusion equipment, matrigel channel units, a medium channel and four indirect contact culture chambers, allowing four types of cells to simultaneously interact through soluble biological factors and metabolites. With this system, bladder cancer cells (T24) with a tendency to form a 'reticular' structure under 3 dimensional culture conditions were observed in real time. The microenvironment characteristics of paracrine interactions and cell motility were successfully simulated in this system. The phenotype change process in stromal cells was successfully reproduced in this system by testing the macrophage effector molecule Arg-1. Arg-1 was highly expressed in the simulated tumor microenvironment group. To develop "precision medicine" in bladder cancer therapy, bladder cancer cells were treated with different clinical 'neo-adjuvant' chemotherapy schemes in this system, and their sensitivity differences were fully reflected. This work provides a preliminary foundation for neo-adjuvant chemotherapy in bladder cancer, a theoretical foundation for tumor microenvironment simulation and promotes individual therapy in bladder cancer patients.