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Psychological stress may lead to erectile dysfunction (ED), and inflammation has been evaluated as a major contributing factor. The goal of this study was to investigate the effects of etanercept (ETN), an anti-tumor necrosis factor α (TNF-α) protein, on cavernosal function in the unpredictable chronic mild stress (UCMS) rat model of depression. Animals were divided into 4 groups: animals not exposed to UCMS, animals not exposed to UCMS and treated with ETN, animals exposed to UCMS, and animals treated with ETN while exposed to UCMS. UCMS significantly impaired the neurogenic and endothelium-dependent relaxation responses; reduced cavernosal endothelial nitric oxide (NO) synthase (eNOS) and neuronal NO synthase (nNOS) expressions; decreased testosterone levels; enhanced systemic levels of corticosterone, TNF-α, interleukin 1β (IL-1β), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule 1 (ICAM-1); and also increased cavernosal levels of TNF-α, IL-1β, and IL-6 in rats. ETN administration restored NO-mediated neurogenic and endothelium-dependent relaxation responses of the corpus cavernosum, increased cavernosal eNOS and nNOS expressions, enhanced testosterone levels, and decreased corticosterone levels in UCMS-exposed rats. Also, systemic inflammatory markers and cavernosal proinflammatory cytokine levels were reduced by ETN. Our results demonstrate the role of TNF-α-mediated inflammation in the development of depression and ED in rats exposed to chronic stress.

We investigated the effect of resveratrol on endothelial and neuronal nitric oxide synthase (eNOS and nNOS) expression in the corpus cavernosum from chronic unpredictable mild stress (CUMS)-exposed rats in order to examine possible role of proinflammatory cytokines, which might play a role on erectile dysfunction (ED). Rats were randomly and equally divided into four groups such as control, control+resveratrol, CUMS and CUMS + resveratrol (20 mg/kg/day, i.p/8 weeks). Sucrose intake and forced swimming tests were used to evaluate depressive-like behaviors. nNOS, eNOS expressions, inflammatory markers, corticosterone and testosterone levels were analyzed either in blood samples and/or penile tissues. CUMS-exposed rats displayed depressive-like behaviors, reduced penile nNOS and eNOS expressions, and serum testosterone levels and enhanced serum and penile tissue levels of proinflammatory markers compared to controls. Resveratrol reversed depressive-like behaviors and suppressed serum and penile levels of proinflammatory markers, increased nNOS and eNOS expressions and testosterone levels in CUMS-exposed rats. Resveratrol exerted antidepressant-like effects and protected the development of CUMS-induced impairment of cavernosal eNOS and nNOS expressions associated with ED, which might be related to its anti-inflammatory action.

Cardiomyogenic differentiation from mesenchymal stem cells has emerged as a novel approach for repair of damaged myocardium. Cell transplantation through direct cell injection is not an optimal method due to the lack of cell-extracellular matrix interactions. In the present study, differentiation potential of human adipose-derived stem cells (ASCs) to cardiomyocytes has been investigated by growing them on hyaluronic acid/gelatin (HA/G) plasma gels and coverslips and supplementing the growth medium with chemical modifiers (activin-a, BMP-4, insulin, valproic acid, and 5-azacytidine) in various combinations. The HA/G plasma gels were produced from human blood plasma-derived fibrinogen, gelatin, and human umbilical cord-derived hyaluronic acid. A networkbased approach was employed to select marker genes for cardiomyogenic differentiation, and the expression levels of three markers (GATA4, TBX5, and cTnI) were followed by RT-qPCR to investigate the cardiomyogenic differentiation potential of ASCs. Results indicated that each combination of chemical modifiers led to different expression levels in the aforementioned cardiac markers, and this was material-dependent, too. The cardiac gene expression on HA/G plasma gels in the presence of activin-a + BMP-4 or insulin + valproic acid was more pronounced than in the presence of 5-azacytidine only, and scaffold and chemical modifier combinations were crucial for cardiomyogenic differentiation.

Introduction: Middle ear cholesteatoma is a benign disease with invasive and destructive clinical behaviors. It increases the rate of both chronic otitis media complications and revision surgeries. The most effective treatment of middle ear cholesteatoma is surgical excision, and there is no medical treatment for this disease. Exploring new medical treatment options may help to create treatment alternatives instead of surgery. Materials and Methods: Required cholesteatoma tissues for cell culture were excised from 4 different participants who underwent surgery in our clinic and agreed to give tissue for the study. Cholesteatoma-derived keratinocytes and fibroblasts were cocultured in temperature-sensitive culture dishes to make a three-dimensional (3D) cholesteatoma model. Then, the effects of 1% and 2% diclofenac sodium on viability and cell proliferation rates were examined using WST-1 and annexin-V tests. Results: Cell viability and proliferation rates were found to be lower and apoptosis rates were higher in the diclofenac sodium group versus the negative and positive control groups. Conclusion: In this present study, we described a new 3D cholesteatoma cell culture model developed using cell sheet technology and demonstrated the efficacy of diclofenac sodium on cholesteatoma for the first time in the literature. It may be used in patients with chronic otitis media with cholesteatoma, but further studies investigating ototoxic and neurotoxic effects of this molecule are needed.