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Bladder cancer is a urothelial malignancy. Bladder cancer starts in the urothelial cells lining the inside of the bladder. The 5-year recurrence rate for bladder cancer ranges from 31% to 78%, and the progression rate is approximately 45%. To treat bladder cancer, intravesical drug therapy is often used. Leonurus artemisia extract (LaE) was obtained from medicinal samples of Chinese motherwort Scientific Chinese Medicine; L. artemisia has various biological effects. This study investigated the impact of LaE on human bladder cancer cells (the BFTC-905 cell line) and the molecular mechanism underlying apoptosis resulting from the activation of cell signal transduction pathways in bladder cancer cells. A cell counting kit-8 (CCK-8) assay was used to determine the effect of LaE on cell growth. The effect of LaE on migration ability was observed using a wound healing assay. The effects of LaE on the cell cycle, reactive oxygen species production, and apoptosis were investigated. Western blot analysis detected apoptosis-related and mitogen-activated protein kinase signaling pathway-related protein concentrations. At non-toxic concentrations, LaE inhibited the proliferation of BFTC-905 cells in a concentration-dependent manner, and the half-maximal inhibitory concentration (IC50) was 24.08172 µg/µL. LaE impaired the migration ability of BFTC-905 cells. LaE arrested the cell cycle in the G1 and G0 phases, increased reactive oxygen species production, and induced apoptosis. LaE increased Bax and p-ERK concentrations and decreased Bcl-2, cleaved caspase-3, and p-p38 concentrations. No differences in PARP, C-PARP, vimentin, e-cadherin, p-JNK, or TNF-alpha concentrations were observed. These results suggest that LaE inhibits the proliferation of human bladder cancer cells. Moreover, the mitogen-activated protein kinase signaling pathway is involved in the inhibition of the proliferation of BFTC-905 cells.

In Taiwan, the incidence of upper-tract urothelial carcinomas (UTUCs) is higher than in western countries (20%–31% vs. 5%–10%), as is bilateral disease. The standard management for high-grade UTUC is radical nephroureterectomy with bladder cuff excision and regional lymphadenectomy. The challenges in managing bilateral UTUCs are how to retain renal function and avoid permanent hemodialysis. We present two cases of developed bilateral high-grade renal pelvis urothelial carcinoma, cT3N0M0 stage III, that revealed excellent results in tumor regression after three cycles of half-dose pembrolizumab. One case received unilateral retroperitoneal laparoscopic nephroureterectomy with bladder cuff excision; thereafter, renal function has been good until now, and the remaining right kidney has been free of tumor recurrence in the 3 years of follow-up. The other patient, however, expired from an immune-related adverse event (irAE) 22 days after the third cycle of pembrolizumab, although tumor remission was evident also. Neoadjuvant pembrolizumab alone could be a potential strategy in positive of selected biomarkers for high-grade bilateral UTUC with remaining neglectable nephrotoxicity and may avoid permanent hemodialysis.

Interstitial cystitis/bladder pain syndrome (IC/BPS), which is characterized by bladder pain and irritative voiding symptoms, is a frustrating disease without effective treatment. The cause is still largely not understood, although urothelium ischemia/hypoxia, apoptosis, denudation, and infiltration of inflammatory cells are common histopathological findings. The current uncertainty regarding the etiology and pathology of IC/BPS has a negative impact on its timely and successful treatment; therefore, the development of new treatment modalities is urgently needed. Herein, we present advances in our knowledge on this topic and review the potential application of regenerative medicine for the treatment of IC/BPS. This article provides information on the basic characteristics and clinical evidence of stem cells, platelet-rich plasma (PRP), and low-energy shock waves (LESWs) based on a literature review with a search strategy for articles related to IC/BPS, stem cells, PRP, and LESW published in MEDLINE and PubMed. Stem cells, PRP, and LESW, which modulate inflammatory processes and promote tissue repair, have been proven to improve bladder regeneration, relieve bladder pain, inhibit bladder inflammation, and increase bladder capacity in some preclinical studies. However, clinical studies are still in their infancy. Based on the mechanisms of action of stem cells, PRP, and LESW documented in many preclinical studies, the potential applications of regenerative medicine for the treatment of IC/BPS is an emerging frontier of interest. However, solid evidence from clinical studies remains to be obtained.

Abstract Background Current advancements in neoadjuvant therapy and total mesorectal excision have engendered increased local control. However, the survival benefit of preoperative radiotherapy (RT; 5 × 5 Gy) in rectal cancer patients remains inadequate, primarily because of systemic recurrence. In this retrospective single-center study, the effects of monthly tegafur–uracil maintenance (≥6 cycles) after 12 fluorouracil-based adjuvant chemotherapy cycles on 3-year relapse-free survival (RFS) was estimated in ypStage III rectal cancer patients. Methods Of ypStage III rectal cancer patients who received preoperative RT (5 × 5 Gy) in January 2006–December 2015, those who had ypStage III cancer after preoperative radiation, radical resection, and postoperative chemotherapy were enrolled; excluded patients had ypStage I and II rectal cancer, had double cancer, had synchronous distant metastasis, had local excision, received preoperative chemoradiation, and were lost to follow-up within 1 year after cancer treatment. Included patients received either maintenance therapy or observation after postoperative chemotherapy. The primary endpoint was the effect of maintenance therapy on 3-year RFS. We set the median follow-up duration to be 69.7 (range, 15.4–148.3) months. Results Of 259 ypStage III rectal cancer patients, 102 (59 men and 43 women) were enrolled based on the inclusion criteria. The maintenance and observation groups comprised 55 and 57 patients, respectively (mean age = 62.2 and 65.7 years, respectively; p = 0.185). The 3-year RFS observed in the maintenance group (85.1%) was longer than that observed in the observation group (67.5%; p = 0.039). Multivariate analysis proved the following to be independent prognostic factors for RFS: higher metastatic lymph node ratio (LNR ≥0.3), tegafur–uracil maintenance (≥6 cycles), and lower rectal cancer (

Radiotherapy (RT) is the main treatment modality for prostate cancer (PCa). This study investigated the role of IL-6 in biological sequelae following irradiation and highlighted the effects of 1α,25-dihydroxyvitamin D3 (calcitriol) on the radiation response of PCa and its relationship with IL-6 signaling. Human and murine PCa cell lines were used to examine the response to irradiation in vitro and in vivo. The relationship of IL-6 expression with clinicopathologic characteristics in 104 PCa patients treated with definite RT was also examined. We also investigated the changes in radiation response after calcitriol supplementation and the relationship between calcitriol and IL-6 signaling by conducting cellular and animal experiments. Based on clinical samples, the positivity of IL-6 staining is a significant predictor of biochemical failure-free survival for PCa patients treated with definite RT. Data from preclinical models showed that inhibition of IL-6 increased the response of PCa to radiation, which was associated with increased oxidative DNA damage, attenuated EMT and MDSC recruitment, and decreased tumor regrowth. Moreover, increased vitamin D3 levels by calcitriol supplementation or induction by UVB-radiation was associated with inhibited IL-6 signaling and increased the response to irradiation observed in animal models. These data demonstrate that IL-6 play a critical role in the radiation response of PCa, which involved tumor cell killing and altering the tumor microenvironment. Directly targeting IL-6 signaling or vitamin D3 supplement with oral or light treatment could be a promising strategy to increase the response of PCa to radiation.

Introduction: Hyperlipidemia is associated with an increased risk of erectile dysfunction (ED) mediated by endothelial damage. Platelet-rich plasma (PRP) contains numerous angiogenic growth factors. Currently, evidence supporting the use of PRP for ED treatment is limited. Aim: We investigated PRP in a rat model of hyperlipidemia-associated ED. Methods: Thirty 2-month-old male Sprague–Dawley rats were randomly divided into 3 groups. 20 rats were fed a high-fat diet for 5 months and were randomly divided into 2 groups: (i) rats in the H group received supernatant injection into the corpus cavernosum weekly for 4 weeks; (ii) rats in the H + PRP group received PRP injection into the corpus cavernosum weekly for 4 weeks. 10 rats were fed a standard diet for 5 months and received supernatant injection into the corpus cavernosum weekly for 4 weeks (N group). 7 days after the 4th injection, all rats underwent erectile function testing and then euthanasia. Main outcome measures: Erectile function was evaluated by measuring intracavernous pressure (ICP) and mean arterial pressure (MAP). Serum and penile tissue were collected for metabolic variable assessment and histochemical examination, respectively. Results: Intracavernous pressure/MAP and area under the curve/MAP ratios were significantly higher in the N and H + PRP groups than in the H group. Insulin-like growth factor-1, brain-derived neurotrophic factor, and vascular endothelial growth factor levels were significantly higher in the H + PRP group than in the N and H groups. Corporal neuronal nitric oxide synthase, endothelial nitric oxide synthase, and endothelial cells were weakly expressed in the H group compared with the N and H + PRP groups. Intracorporal oxidative stress and apoptotic index were significantly higher in the H group than in the N and H + PRP groups. Conclusions: This preclinical evidence suggests that clinical trials of PRP in men with ED should be considered. PRP may play a role in ED management.Huang YC, Wu CT, Chen MF, et al. Intracavernous Injection of Autologous Platelet-Rich Plasma Ameliorates Hyperlipidemia-Associated Erectile Dysfunction in a Rat Model. Sex Med 2021;9:100317.

Currently, the coronavirus disease 2019 (COVID-19) pandemic is still an ongoing and constant medical issue, and with upcoming new variants, vaccinations and boosters remain important. The safety of vaccines in patients after kidney transplantation is an essential problem, with thrombosis being one of the severe side effects and vaccine-induced immune thrombotic thrombocytopenia (VITT) revealed as the most commonly reported syndrome for thromboembolic events following COVID-19 vaccination. Here, we present two cases of kidney transplantation developing pulmonary embolism post-Moderna vaccination within 30 days without thrombocytopenia. The first case was a 52-year-old man with history of type II diabetes, hypertension and hyperlipidemia who had had cadaveric kidney transplantation in September 2008, where right leg swelling with claudication occurred 23 days after the second Moderna vaccination. The second case was a 57-year-old man with history of type II diabetes and glaucoma who had had living-related kidney transplantation in April 2013 and then complained of exertional dyspnea 26 days after administration of the third Moderna vaccine. The advantages of vaccination even in immunocompromised patients far outweigh the disadvantages, although clinicians must understand the risks of deep-vein thrombosis or even pulmonary embolism for such patients, which might not occur after just the first vaccination.

Background: The aim of this study was to evaluate practicable predictors of 5-year disease-free survival (DFS) and impact of 5-fluorouracil (5-FU)-based adjuvant chemotherapy in stage IIa and IIb colon cancer. Materials and Methods: A total of 1474 patients with stage II colon cancer were enrolled in study. The independent predictors of 5-year DFS and the benefits of adjuvant chemotherapy were analyzed for patients with stage IIa (n = 771) and IIb (n = 703). Results: The incidences of pretreatment anemia, hypoalbuminemia, emergent surgery, and lymphovascular invasion (LVI) corresponded significantly to an advanced T-stage in patients with stage II colon cancer. Although the incidence of surgical morbidity was not different between stage IIa and IIb, stage II patients with hypoalbuminemia had a higher incidence of surgical morbidity than did those with normal serum albumin (17.2% vs. 9.6%, P < 0.001). The co-independent survival predictors in patients with stage IIa and IIb colon cancer were carcinoembryonic antigen (CEA < 5 ng/mL, P = 0.007 and 0.043), serum albumin (≥3.5 g/dL, P < 0.001 and P = 0.025), and nonsurgical morbidity (P < 0.001, both). Suboptimal lymph node harvest (

To investigate postoperative complications and oncologic outcomes of prophylactic nephroureterectomy and/or cystectomy in dialysis patients with urothelial carcinoma (UC), we retrospectively reviewed the records of dialysis patients with UC and a final status of complete urinary tract extirpation (CUTE, i.e., the removal of both kidneys, ureters, and bladder) between January 2004 and December 2015. Patients undergoing dialysis after initial radical nephroureterectomy and/or cystectomy were excluded. Eighty-four and 27 dialysis patients, undergoing one-stage and multi-stage CUTE, were enrolled in this study, respectively. Demographic, medical, perioperative, and pathologic features were collected to determine variables associated with oncologic outcomes. Although there was no significant difference in mortality between the 2 groups (p = 0.333), all 5 (4.5%) patients with Clavien–Dindo grade 5 complications were from the one-stage CUTE group. On multivariate logistic regression analysis, advanced age (p = 0.042) and high Charlson comorbidity index (CCI) (p = 0.000) were related to postoperative major complications. Compared with multi-stage CUTE, one-stage CUTE had no overall, cancer-specific, and recurrence-free survival benefits (all p > 0.05). According to multivariate analysis with Cox regression, age > 70 years (HR 2.70, 95% CI 1.2–6.12; p = 0.017), CCI ≥ 5 (HR 2.16, 95% CI 1.01–4.63; p = 0.048), and bladder cancer stage ≥ 3 (HR 12.4, 95% CI 1.82–84.7; p = 0.010) were independent, unfavorable prognostic factors for the overall survival. One-stage CUTE is not associated with superior oncologic outcomes, and all perioperative mortalities in our series occurred in the one-stage CUTE group. Our data do not support prophylactic nephroureterectomy and/or cystectomy for uremic patients with UC.

Objective: To examine the 10-year risk of stroke among patients with acute urinary retention (AUR) in Taiwan, using a population-based dataset. Methods: This retrospective cohort study included 38,433 patients aged > 50 years with AUR, with or without catheterization, and 38,433 matched patients without AUR (controls) sourced from the Longitudinal Health Insurance Database from 2001 to 2010. Cox proportional hazards regression was used to evaluate the association between AUR and the risk of stroke during the subsequent 10-year follow-up period, after adjusting for sociodemographic characteristics, hypertension, diabetes, hyperlipidemia, coronary heart disease, and urinary tract infection. Results: Of the 38,433 patients with AUR, 2805 (7.3%) had strokes during the follow-up period compared with 1077 (2.8%) controls (crude hazard ratio, 2.69; 95% confidence interval, 2.5–2.88). After adjusting for potential confounders, risk of stroke was increased in patients with AUR (hazard ratio, 2.36; 95% confidence interval, 2.19–2.53). There was a significant difference in the 10-year stroke-free survival rate between the patients with and without AUR (p

Tobacco use is associated with erectile dysfunction (ED) via a number of mechanisms including vascular injury and oxidative stress in corporal tissue. Adipose derived stem cells (ADSC) have been shown to ameliorate vascular/corporal injury and oxidative stress by releasing cytokines, growth factors and antioxidants. We assessed the therapeutic effects of intracavernous injection of ADSC in a rat model of tobacco-associated ED. Thirty male rats were used in this study. Ten rats exposed to room air only served as negative controls. The remaining 20 rats were passively exposed to cigarette smoke (CS) for 12 weeks. At the 12-week time point, ADSC were isolated from paragonadal fat in all rats. Amongst the 20 CS exposed rats, 10 each were assigned to one of the two following conditions: (i) injection of phosphate buffered saline (PBS) into the corpora cavernosa (CS+PBS); or (ii) injection of autologous ADSC in PBS into the corpora cavernosa (CS+ADSC). Negative control animals received PBS injection into the corpora cavernosa (normal rats [NR] + PBS). After injections all rats were returned to their previous air versus CS exposure state. Twenty-eight days after injection, all rats were placed in a metabolic cage for 24-hour urine collection to be testing for markers of oxidative stress. After 24-hour urine collection all 30 rats also underwent erectile function testing via intracavernous pressure (ICP) testing and were then sacrificed. Corporal tissues were obtained for histological assessment and Western blotting. Mean body weight was significantly lower in CS-exposed rats than in control animals. Mean ICP, ICP /mean arterial pressure ratio, serum nitric oxide level were significantly lower in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Urine markers for oxidative stress were significantly higher in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Mean expression of corporal nNOS and histological markers for endothelial and smooth muscle cells was significantly lower, and tissue apoptotic index significantly higher, in the CS+PBS group compared to the NR+PBS and CS+ADSC groups. Our findings confirm that chronic tobacco exposure causes ultrastructural damage to the corporal tissue and increases systemic oxidative stress states. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential therapy for tobacco-related ED.

Cigarette use is an independent risk factor for the development of erectile dysfunction (ED). While the association between chronic smoking and ED is well established, the fundamental mechanism(s) of cigarette-related ED are incompletely understood, partly due to no reliable animal model of smoking-induced ED. The present study was designed to validate an in vivo rat model of chronic cigarette-induced ED. Forty 12-week old male Sprague-Dawley rats were divided into 4 groups. Ten rats served as control group and were exposed only to room air. The remaining 30 rats were passively exposed to cigarette smoke (CS) for 4 weeks (n = 10), 12 weeks (n = 10), and 24 weeks (n = 10). At the 24-week time point all rats were assessed with intracavernous pressure (ICP) during cavernous nerve electrostimulation. Blood and urine were collected to measure serum testosterone and oxidative stress, respectively. Corporal tissue was assessed by Western blot for neuronal nitric oxide synthase (nNOS). Penile tissues were subjected to immunohistochemistry for endothelial, smooth muscle, and apoptotic content. Mean arterial pressure (MAP) was significantly higher in 24-week cigarette exposed animals compared to the control animals. Mean ICP/MAP ratio and cavernosal smooth muscle/endothelial contents were significantly lower in the 12- and 24-week rats compared to control animals. Oxidative stress was significantly higher in the 24-week cigarette exposed group compared to control animals. Mean nNOS expression was significantly lower, and apoptotic index significantly higher, in CS-exposed animals compared to control animals. These findings indicate that the rat model exposure to CS increases apoptosis and oxidative stress and decreases nNOS, endothelial and smooth muscle contents, and ICP in a dose dependent fashion. The rat model is a useful tool for further study of the molecular and cellular mechanisms of CS-related ED.

Diabetes is usually asymptomatic in its early stage. Early diagnosis may improve outcomes by enabling initiation of treatment before end organ damage has progressed. The aim of this study was to determine whether the clinical sign of phimosis with preputial fissures is predictive of type 2 diabetes in patients not previously diagnosed with diabetes. Twenty-eight patients with acquired phimosis and preputial fissures were collected prospectively. Twenty-eight controls with acquired phimosis without preputial fissures were selected. Statistically significant differences were found in body mass index, random plasma glucose, glucosuria and glycosylated haemoglobin levels, but not in age, family history of diabetes, hypertension and classical hyperglycaemic symptoms. Diabetes was confirmed in all 28 patients in the preputial fissures group, but only 2 (7.1%) patients in the non-preputial fissures group (p < 0.0001). In conclusion, phimosis with preputial fissures may be a specific sign of undiagnosed diabetes mellitus. [ABSTRACT FROM AUTHOR]

Introduction. Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. Aim. To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. Methods. Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2′-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology. Main Outcome Measures. Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. Results. Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. Conclusions. Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED. Huang Y-C, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, and Lin C-S. The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med 2010;7:1391–1400. [ABSTRACT FROM AUTHOR]

Background aims The thymidine analog bromodeoxyuridine (5-bromo-2-deoxyuridine; BrdU) has been used widely to label cells in culture and in tissue. The labeled cells can also be tracked when transplanted into a suitable host. In the present study we tested a new thymidine analog, 5-ethynyl-2-deoxyuridine (EdU), for labeling and tracking of mesenchymal stromal cells (MSC), specifically adipose tissue-derived stem cells (ADSC). Methods Labeling of ADSC was examined for the dosage effect of EdU and stability of label by Alexa-594 staining followed by fluorescence microscopy. Labeling of various organs/tissues was done by intraperitoneal injection of EdU and examined by histology and fluorescence microscopy. Tracking of ADSC was done by intratissue or intravenous transplantation of EdU-labeled ADSC into various tissues and examined by histology and fluorescence microscopy. Results EdU was incorporated specifically into the nucleus in approximately 50% of ADSC and the percentage of cells that remained fully labeled declined with time. Peritoneal injection of EdU resulted in the appearance of EdU-positive cells in most organs and tissues. In the intestine, EdU-positive cells were found in both the epithelium and connective tissues 7 h after injection. Long-term (2-6 week) follow-ups found EdU-positive cells only in the connective tissue. Tracking of ADSC was successful in tissues 10 weeks after intratissue or intravenous transplantation. Conclusions Cell labeling with EdU in culture or living animals can be performed easily. The detection of EdU label requires no harsh treatment or immunologic reaction, as detection of BrdU label does. EdU can be used for long-term tracking of ADSC. [ABSTRACT FROM AUTHOR]

OBJECTIVE To evaluate the effect of desmopressin on nocturia, based on patients’ subjective scoring of nocturia, as desmopressin is widely used to treat nocturnal enuresis and nocturnal polyuria. PATIENTS AND METHODS We investigated a specific subgroup of 28 men with benign prostate obstruction and nocturia who were treated with desmopressin. Patients with nocturnal polyuria were excluded. All the patients were refractory to treatment with antimuscarinics or anticholinergics, e.g. oxybutynin, tolterodine, and propantheline bromide. We assessed the effect of desmopressin using a quantitative nocturia score and analysed its synergistic effect with α-blockers. RESULTS The mean frequency of nocturia was 6.1 before desmopressin and most (86%) patients had an improvement in nocturia within 1–12 weeks of treatment with desmopressin. There was a 43% reduction in nocturia after using desmopressin ( P < 0.001). The correlation coefficient between the number of nocturnal voids and the reduction in nocturia after treatment with desmopressin was 0.756, indicating that the more severe the nocturia, the more effective was desmopressin. CONCLUSIONS Desmopressin is effective for refractory nocturia in elderly men with no nocturnal polyuria, and has limited side-effects. [ABSTRACT FROM AUTHOR]

Introduction. Transforming growth factor-β1 (TGF-β1) has been implicated in the pathogenesis of Peyronie's disease (PD) and also plays a role in collagen and elastin metabolism. Pentoxifylline (PTX) antagonizes the effects of TGF-β1 and has been utilized in our clinic for the management of PD. Aim. We studied the effects of TGF-β1 and PTX on collagen metabolism and elastogenesis in tunica albuginea-derived fibroblasts (TADFs). Methods. TADFs from men with and without PD were cultured and treated with TGF-β1 and PTX as monotherapy at differing concentrations and time points. Combination treatment (TGF-β1 followed by PTX and vice versa) was also investigated. Main Outcome Measures. Cell proliferation assay, enzyme-linked immunosorbent assay, and immunohistochemistry were utilized to assess the impact of TGF-β1 and PTX on TADF with respect to elastin and collagen I metabolism. Results. PTX inhibited fibroblast proliferation at doses of 100 µM. TGF-β1 stimulated elastogenesis and collagen I fiber deposition in TADF in a dose- and time-dependent fashion. Pretreatment with PTX dramatically attenuated TGF-β1-mediated elastogenesis and collagen fiber deposition in TADF from men with and without PD. Interestingly, production of collagen I was higher in untreated Peyronie's tunica (PT) cells relative to normal tunica (NT) cells; furthermore, PTX attenuated collagen production to levels similar to untreated control TADF in PT cells but not in NT cells, suggesting important intrinsic differences between PT and NT cells. Conclusion. Both elastin and collagen are upregulated by TGF-β1 in TADF. This likely contributes to the PD phenotype. Pretreatment with PTX attenuates both collagen fiber deposition and elastogenesis in TADF exposed to TGF-β1; these effects suggest a useful role for PTX in the management of PD. Shindel AW, Lin G, Ning H, Banie L, Huang Y-C, Liu G, Lin C-S, and Lue TF. Pentoxifylline attenuates TGF-β1 stimulated collagen deposition and elastogenesis in human tunica albuginea-derived fibroblasts Part 1: Impact on extracellular matrix. J Sex Med 2010;7:2077–2085. [ABSTRACT FROM AUTHOR]

Introduction. Epimedium species (aka horny goat weed) have been utilized for the treatment of erectile dysfunction in Traditional Chinese Medicine for many years. Icariin (ICA) is the active moiety of Epimedium species. Aim. To evaluate the penile hemodynamic and tissue effects of ICA in cavernous nerve injured rats. We also studied the in vitro effects of ICA on cultured pelvic ganglia. Methods. Rats were subjected to cavernous nerve injury and subsequently treated for 4 weeks with daily gavage feedings of a placebo solution of normal saline and Dimethyl sulfoxide (DMSO) vs. ICA dissolved in DMSO at doses of 1, 5, and 10 mg/kg. A separate group underwent a single dose of ICA 10 mg/kg 2 hours prior to functional testing. Functional testing with cavernous nerve stimulation and real-time assessment of intracavernous pressure (ICP) was performed at 4 weeks. After functional testing, penile tissue was procured for immunohistochemistry and molecular studies. In separate experiments, pelvic ganglia were excised from healthy rats and cultured in the presence of ICA, sildenafil, or placebo culture media. Main Outcome Measure. Ratio of ICP and area under the curve (AUC) to mean arterial pressure (MAP) during cavernous nerve stimulation of subject rodents. We also assayed tissue expression of neuronal nitric oxide synthase (nNOS), eNOS: endothelial nitric oxide synthase (eNOS), calponin, and apoptosis via immunohistochemistry and Western blot. Serum testosterone and luteinizing hormone (LH) were assayed using enzyme-linked immunosorbant assay (ELISA). Differential length of neurite outgrowth was assessed in cultured pelvic ganglia. Results. Rats treated with low-dose ICA demonstrated significantly higher ICP/MAP and AUC/MAP ratios compared with control and single-dose ICA animals. Immunohistochemistry and Western blot were revealing of significantly greater positivity for nNOS and calponin in penile tissues of all rats treated with ICA. ICA led to significantly greater neurite length in cultured specimens of pelvic ganglia. Conclusion. ICA may have neurotrophic effects in addition to known phosphodiesterase type 5 inhibiting effects. Shindel AW, Xin Z-C, Lin G, Fandel TM, Huang YC, Banie L, Breyer BN, Garcia MM, Lin C-S, and Lue TF. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed ( Epimedium spp.) in vitro and in vivo. J Sex Med 2010;7:1518–1528. [ABSTRACT FROM AUTHOR]