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Skin Fragility: Perspectives on Evidence-based Therapies
Abstract: The term skin fragility disorders describes a group of conditions in which the structural integrity of the skin is compromised and its resistance to external shear forces diminished. Skin fragility can have different causes, ranging from genetic variations to inflammatory or physical phenomena. The genetic skin fragility disorders, collectively called epidermolysis bullosa, serve as a paradigm for the study of causes and mechanisms of skin fragility. Recent biomedical research has revealed substantial genetic heterogeneity of the epidermolysis bullosa group, delivered ample new knowledge on its pathophysiology, and facilitated the design of evidence-based therapeutic strategies. The therapy development process extends from in vitro testing to preclinical validation in animal models, and clinical trials. This article reviews different approaches to curative and symptom-relief therapies, and appraises their status and perspectives for clinical implementation
Donor-dependent Variation and Bias of Transforming Growth Factor-u03b2 Activating Mechanisms in Recessive Dystrophic Epidermolysis Bullosa
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe hereditary skin blistering disease. Clinically, individuals with RDEB are characterized by fragile skin and blister formations followed by devastating fibrosis. The fibrosis in RDEB has been reported to be driven by transforming growth factor-beta (TGF-uf062) signaling and we previously demonstrated that reduced TGF-uf062uf020activity lead to significantly slower progression of fibrosis in RDEB model mice. Nevertheless, unbiased targeting of TGF-uf062 activity in skin could have dire consequences as TGF-uf062uf020signaling supports dermal-epidermal communication to main skin homeostasis. Therefore, there is a need to better charac...
