Assessment of serum vitamin D level and seminal vitamin D receptor gene methylation in a sample of Egyptian men with idiopathic infertility.

Vitamin D deficiency has been linked with different health problems including male infertility. Its function is mediated by the vitamin D receptor, which acts as a transcription factor. Epigenetic mechanisms such as DNA methylation may affect the vitamin D receptor gene and result in gene silencing. The present study aimed to assess serum vitamin D level and seminal methylation of vitamin D receptor gene in idiopathic male infertility. Blood and semen samples were collected from 60 men with idiopathic infertility and 40 healthy fertile men. Vitamin D levels were detected using enzyme-linked fluorescent assay technique and methylation status was assessed by methylation-specific PCR. Results revealed that serum levels of 25OHD were significantly lower in patients compared to controls. Positive correlation was found between serum level of 25OHD and sperm concentration in patients group and progressive motility in total studied group. Methylation of vitamin D receptor gene was significantly higher in patients compared to control group. Negative correlation was found between methylation of vitamin D receptor gene and both sperm concentration and progressive motility in total studied group. Results of the present study suggest that vitamin D deficiency and vitamin D receptor gene methylation may be involved in aetiopathogenesis of idiopathic male infertility.

IFN-α and TNF-α serum levels and their association with disease severity in Egyptian children and adults with alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune skin disease characterized by abnormal levels of several cytokines, such as interferon alpha (IFN-α) and tumor necrosis factor-alpha (TNF-α), which are T-helper type 1 cytokines that have important roles in the pathogenesis of AA. The aim of our study was to correlate circulating IFN-α and TNF-α levels with disease severity, activity, and clinical type in patients with AA and to evaluate the relationship between the two cytokines. METHODS: We investigated serum IFN-α and TNF-α levels in 72 patients with AA (35 children and 35 adults) and 75 healthy control individuals (34 children and 41 adults) using the enzyme-linked immunosorbent assay (ELISA) technique. We evaluated AA severity using the Severity of Alopecia Tool (SALT) and determined the activity based on dermoscopic criteria of disease activity. RESULTS: Serum IFN-α and TNF-α concentrations were significantly higher in the patients than in the controls. There was a significant positive correlation between serum IFN-α and TNF-α levels in all patients with alopecia areata, as well as between serum TNF-α levels and disease severity in all patients and in children. CONCLUSIONS: Our results support the association between IFN-α and TNF-α levels and AA and suggest that TNF-α might be related to disease severity.

Altered Functional Expression of ß-Adrenergic Receptors in Rhesus Monkey Embryonic Stem Cell-Derived Cardiomyocytes.

Pluripotent stem cells have demonstrated the potential to generate large numbers of functional cardiomyocytes (CMs) from different cell sources. Besides Wnt signaling, additional pathways are involved in early cardiac development and function. To date however, no study exists showing the effects of perturbing the canonical Wnt pathway using nonhuman primate embryonic stem (ES) cells. In this study, we investigated the effect of canonical Wnt inhibition during differentiation of nonhuman primate ES cell-derived CMs under defined, growth factor conditions. Rhesus monkey ES (rES) cells were differentiated into spontaneously beating CMs in the absence (control) or presence (treated) of Wnt inhibitor Dickkopf1 (DKK1), vascular endothelial growth factor, and basic fibroblast growth factor combined or added in a sequential manner during differentiation. Quantification and functional characterization of CMs were assessed by molecular and electrophysiological techniques. Analysis revealed no difference in average ratio of spontaneously beating clusters in both control and treated groups. However, the percentage of CMs was significantly reduced and the expressions of specific cardiac markers tested were also decreased in the treated group. Interestingly, we found that in CMs obtained from treated group, ß-adrenergic receptors (ß-ARs) were less expressed, their function was altered and electrophysiological studies revealed differences in action potential responsiveness to ß-AR stimulation. We demonstrated that the Wnt/ß-catenin pathway inhibitor, DKK1 associated with other growth factors repressed functional expression of ß-ARs in rES cell-derived CMs. Thus, control of this pathway in each cell line and source is important for proper basic research and further cell therapy applications.