Histone deacetylase 1 in patients with alopecia areata and acne vulgaris: An epigenetic alteration.

BACKGROUND: Histone deacetylase 1 (HDAC1) belongs to class I histone deacetylases, which are zinc-dependent enzymes that remove the acetyl group from histones and other proteins providing epigenetic regulation of gene expression. It plays an important role in the hair follicle and epidermal homeostasis in addition to its immunomodulatory roles. Alopecia areata (AA) and acne vulgaris are common skin diseases in which epigenetic factors have been proposed. However, studies of epigenetic modifications in both diseases are quite limited. OBJECTIVE: This study aimed at elucidation of HDAC1 deregulation in AA and acne vulgaris. METHODS: A case-control study was conducted on 76 participants: 25 patients with patchy alopecia areata, 26 patients with acne vulgaris and 25 healthy controls. Blood samples were collected for the measurement of HDAC1 level by ELISA. RESULTS: A significant difference in the serum level of HDAC1 was found between the studied groups being highest in the AA group (P = 0.0001). It was significantly higher in the AA group than the acne vulgaris group (P = 0.0001). CONCLUSION: HDAC1 appears to be deregulated in patients with AA and acne vulgaris. This may suggest a potential therapeutic opportunity for HDAC inhibitors for the treatment of such diseases.

Treatment of dystrophic epidermolysis bullosa with bone marrow non-hematopoeitic stem cells: a randomized controlled trial.

Patients with dystrophic epidermolysis bullosa (DEB) have mutations in type VII collagen gene. Type VII collagen is synthesized by keratinocytes and fibroblasts. Based on the ability of bone marrow non-hematopoeitic stem cells (NHBMSC) to develop into fibroblasts, we decided to investigate the use of NHBMSC in the treatment of recessive DEB (RDEB). This study included fourteen patients with RDEB; the first seven of them were given cyclosporine after the infusion of NHBMSC. As cyclosporine has been used for the treatment of RDEB we decided not to use cyclosporine for the second group of seven patients. Skin biopsies from the lesions were studied by electron microscopy before and after treatment. The number of new blisters decreased significantly after treatment in both groups (p = 0.003 and 0.004 respectively) and the rate of healing of new blisters became significantly faster after treatment in both groups (p < 0.001) with no significant difference between the two groups. Electron microscopic examination revealed increased number of anchoring fibrils after treatment in both groups. No major side effects were reported during the 1-year follow-up period. Our findings highlight the efficacy as well as the safety of NHBMSC in the treatment of RDEB.

Upregulation of the miRNA-155, miRNA-210, and miRNA-20b in psoriasis patients and their relation to IL-17.

Psoriasis is an immune-mediated disease, with genetic background and triggering environmental factors; however, several gaps are still present in understanding the intertwined relationship between these elements. Epigenetic mechanisms, including microRNAs (miRNAs), play an important role in the pathogenesis of psoriasis. The relationship between interleukin (IL)-17, a key cytokine in psoriasis, and these epigenetic mechanisms still needs to be elucidated. This study aimed at assessing the expression of miRNA-155, miRNA-210, and miRNA-20b in skin and sera of psoriasis patients in relation to IL-17 levels. For 20 psoriasis patients and 20 matching controls, the expression of miRNA-155, miRNA-210, and miRNA-20b was assessed using real-time polymerase chain reaction (RT-PCR), whereas IL-17/IL-17A levels were measured using quantitative enzyme-linked immunosorbent assay (ELISA) technique. MiRNA-155 expression was significantly higher in lesional skin compared to controls (P = 0.001). MiRNA-210 expression was significantly higher in both, lesional skin (P = 0.010) and sera of patients (P = 0.001) in comparison with controls. A statistically significant positive correlation was found between serum miRNA-210 expression and serum levels of IL-17/IL-17A (P = 0.010, rs = 0.562). MiRNA-20b lesional and non-lesional expression was significantly higher than controls (P < 0.001; P = 0.018). In conclusion, the expression of miRNA-155, miRNA-210, and miRNA-20b is exaggerated in psoriasis and they may be involved in disease pathogenesis. A possible relationship between miRNA-210 and IL-17 may be suggested; however, further studies are still needed to verify this relation.

Assessment of Tissue Level of Histone Deactylase-2 (HDAC-2) in Patients With Mycosis Fungoides.

BACKGROUND: Histone deactylases (HDAC) have a role in the pathogenesis of mycosis fungoides (MF) through their actions on different apoptosis pathways. OBJECTIVE: To assess the possible role played by HDAC-2 in MF by estimating the tissue expression of HDAC2 mRNA in different stages of MF. METHODS: This study included 28 MF patients and 30 controls. The HDAC-2 levels were detected by real-time polymerase chain reaction (PCR). Correlations of HDAC-2 levels with clinical presentation and different stages of MF were analyzed. RESULTS: Mean HDAC-2 level was significantly higher in patients (P < .001) than in controls. HDAC-2 highest mean value was significantly detected in patients with stage IIb, and the lowest mean value was detected in patients with stage Ia (P < .001). CONCLUSION: Up-regulation of tissue HDAC-2 in MF patients might develop a new approach in the understanding of the pathogenesis of MF. Histone deactylases are important targets for molecular cancer therapeutics.

Mycophenolate mofetil: a novel immunosuppressant in the treatment of dystrophic epidermolysis bullosa, a randomized controlled trial.

BACKGROUND: No effective treatment has been found for epidermolysis bullosa dystrophica (EBD). OBJECTIVE: To evaluate the efficacy and safety mycophenolate mofetil (MMF) in treating EBD. METHODS: This randomized controlled double-blinded study included 35 patients with severe generalized EBD. Patients were randomly divided into two groups: group I (18 patients) received cyclosporine therapy (5 mg/kg/day) and group II (17 patients) received MMF therapy (500-1500 mg/day). Clinical assessment was made weekly for 3 months from the start of the treatment. Patients were assessed by measuring the extent of the disease, the % of improvement, assessing the number of new blister formation and the time of complete healing of new blisters. Side effects were recorded when detected. RESULTS: The % of improvement in the disease extent was statistically significantly higher (p = 0.009) in group I (mean ± SD: 59.21 ± 22.676) than in group II (mean ± SD: 44.03 ± 25.71). As regards the number of new blisters and the rate of healing of blisters, there was no statistically significant difference between both groups (p = 0.693 and 0.404, respectively). No serious side effects were reported. CONCLUSION: MMF seems to be a good therapeutic option for the long-term treatment of EBD, it can be a good alternative for patients who cannot tolerate cyclosporine.

Skin tags, leptin, metabolic syndrome and change of the life style.

BACKGROUND: Skin tags (STs), are papillomas commonly found in the neck and in the axillae of middle-aged and elderly people. Metabolic syndrome (MS) is a complex of interrelated risk factors for cardiovascular disease and diabetes. Epidemiologic studies of different ethnic populations have indicated that hyperleptinaemia and leptin resistance are strongly associated with MS. AIM: To study the possible relation of skin tags and leptin levels to MS guided by the International Diabetes Federation (IDF) diagnostic criteria. METHODS: This study included 80 participants, 40 ST patients and 40 apparently healthy controls. Age, sex, waist circumference (WC), body mass index (BMI), smoking status, fasting glucose level, insulin level and insulin resistance were estimated as well as cholesterol, triglycerides, HDL, criteria of MS, and leptin levels. RESULTS: The univariate analysis showed that WC, BMI, fasting glucose, insulin levels, insulin resistance, cholesterol, triglycerides, HDL, and leptin levels were significantly higher in ST patients compared to controls (P<0.001). The multivariate analysis between MS components and ST showed that only high triglyceride levels (OR 1.205/95% CI 1.044-1.391/P=0.011) and low HDL levels (OR 0.554/95% CI 0.384-0.800/P=0.002) were significantly associated with ST. Multivariate linear regression analysis of the predictors of high plasma leptin levels, showed that high triglyceride levels (OR 0.287/95% CI 0.410-3.56/P=0.014), and low HDL levels (OR -0.404/95% CI -8.7 to -2.08/P=0.002) were significant predictors. CONCLUSION: The results of this study suggested that the presence of both ST and hyperleptinaemia in patients with STs may be associated with high levels of triglycerides and low levels of HDL and this could suggest that changing the life style of patients with ST may have a beneficial role.