The combination of optical clearing and LSFM has new applications in dermatology and dermatological research by allowing 3D visualization and analysis of whole human skin biopsies.
OBJECTIVE: The main function of skin is to protect the body from external aggressions. Over time, normal skin ageing is accelerated by external stresses such as smoking, pollution, chemical products and radiation. UV light, in particular UVA, causes DNA damage, apoptosis and morphological modifications, which are responsible for both premature ageing and cancer. The aim of this study was to establish a discriminatory and sufficiently reproducible cutaneous model for evaluating UVA damage, to enable testing for effectiveness of potentially protective compounds. METHODS: The cutaneous model is based on Human skin explants irradiated with UVA. Deleterious effects on epidermis were observed and quantified by haematoxylin-eosin staining and by immunofluorescence of ɣ-H2Ax, cytokeratin 5, involucrin and loricrin protein. Dermis deterioration was evaluated by transmission electronic microscopy and zymography in situ. RESULTS:We were able to observe and quantify deleterious effects associated with UVA irradiation: epidermal and dermal disruption, appearance of Sunburn cells, increased DNA damage and induced apoptosis. The use of this model in the evaluation of protective compounds was first confirmed using sunscreens, then further validated with a panel of active ingredients which showed beneficial effects on epidermis morphology and DNA integrity after UVA exposure. CONCLUSION: We have developed a model and a standardized protocol, based on the use of human skin explants,
In recent years, a number of active materials have been developed to provide anti-aging benefits for skin and, among them, peptides have been considered the most promising candidate due to their remarkable and long-lasting anti-wrinkle activity. Recent studies have begun to elucidate the relationship between the secretion of emotion-related hormones and skin aging. Kisspeptin, a neuropeptide encoded by the KISS1 gene, has gained attention in reproductive endocrinology since it stimulates the reproductive axis in the hypothalamus; however, the effects of Kisspeptin on skin have not been studied yet. In this study, we synthesized Kisspeptin-10 and Kisspeptin-E, which are biologically active fragments, to mimic the action of Kisspeptin. Next, we demonstrated the anti-aging effects of the Kisspeptin-mimicking fragments using UV-induced skin aging models, such as UV-induced human dermal fibroblasts (Hs68) and human skin explants. Kisspeptin-E suppressed UV-induced 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) stimulation leading to a regulation of skin aging related genes, including type I procollagen, matrix metalloproteinases-1 (MMP-1), interleukin-6 (IL-6), and IL-8, and rescued the skin integrity. Taken together, these results suggest that Kisspeptin-E could be useful to improve UV-induced skin aging by modulating expression of stress related genes, such as 11β-HSD1.
Dermatomyositis-related panniculitis (DP) manifests as red subcutaneous, firm and tender plaques, usually on the arms, buttocks, thighs and abdomen. DP is commonly described in textbooks yet there are few reports in the medical literature and there are no guidelines on its best management. Here we present a case of a patient with DP of the neck region. Case Description: A 66-year-old African American woman with a three-year history of dermatomyositis with high titer antinuclear antibody, characteristic pattern of rash, and muscle weakness presented with progressive neck swelling, neck pain, dysphagia, and dyspnea over a period of two months. Physical examination revealed extensive woody induration of the anterior neck region, mild tenderness on palpation on the right side, and decreased range of motion of the neck. CT scan demonstrated extensive soft tissue infiltration in the neck and mediastinum, pleural thickening, as well as a new 1.5 centimeter right lower lobe pulmonary nodule with irregular borders not previously seen on CT scan three months prior. PET scan demonstrated inflammation throughout the mediastinum and into the chest, but no area demonstrated significant avidity consistent with cancer. Flow cytometry was also negative. Histological examination of a neck biopsy demonstrated lobular panniculitis. Based on the histological appearance, a diagnosis of DP was made. Treatment with corticosteroids, dapsone, and colchicine resolved the DP and controlled the dermatomyositis symptoms. Repeat CT scan showed largely complete resolution of the pleural thickening, pulmonary nodule, and mediastinal mass. Conclusion: While cutaneous involvement of dermatomyositis is well described, subcutaneous involvement is a rarely reported clinical finding. This is the first report describing DP in the neck and mediastinal region. The parallel response to corticosteroids in the panniculitis and myositis suggest these processes share a related pathogenesis.
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