ABSTRACT
BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-ß1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1ß and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. CONCLUSIONS: Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients' chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.
Subject(s)
Humans , Epidermolysis Bullosa Dystrophica/genetics , Bandages , Cell Differentiation , Collagen Type VII/genetics , FibroblastsABSTRACT
El ayuno intermitente se ha popularizado como una estrategia alternativa para el control de peso y disminución de algunos parámetros bioquímicos. El propósito de esta revisión sistemática fue evaluar la efectividad del ayuno intermitente en dos protocolos: ayuno en días intermitentes (ADA) y ayuno restringido en el tiempo (ART), sobre el perfil lipídico, composición corporal y presión arterial en adultos. Método: Revisión sistemática basada en ensayos controlados aleatorios consultados en las bases de datos: Web of Science, Scopus, Cochrane Library, Clinical Trials, Proquest y PubMed. Se estudió a adultos mayores de 18 años con cualquier estado nutricional. La intervención correspondió a ayuno intermitente de al menos 16 horas. Se evaluaron riesgos de sesgos según la colaboración de Cochrane. Resultados: Se analizaron seis ensayos clínicos, encontrándose que el protocolo ADA, presente en cuatro de ellos, generó cambios en las variables: triglicéridos, c-HDL, c-LDL, colesterol total, peso, masa magra, masa grasa y presión arterial sistólica, mientras que el protocolo ART, presente en los dos restantes, provocó cambios en las variables: peso, masa grasa, masa magra, triglicéridos, colesterol total, c-LDL, c-HDL y glicemia. Conclusión: La evidencia disponible con ensayos clínicos nos permite sugerir que los protocolos ADA y ART pueden ser una dieta alternativa para adultos. Sin embargo, el ajuste calórico y una adecuada educación sobre estilos de vida saludable muestran resultados similares. Sin perjuicio a esto, el AI puede ser una alternativa para aquellos a quienes les es difícil seguir un patrón dietético con restricción calórica diaria.
Intermittent fasting has become popular as an alternative strategy for weight control and the reduction of some biochemical parameters. The purpose of this systematic review (SR) was to evaluate the effectiveness of intermittent fasting in two protocols: intermittent days fasting (ADA) and time-restricted fasting (ART), on lipid profile, body composition and blood pressure among adults. Methods: SR based on randomized controlled trials consulted in the following databases: Web of Science, Scopus, Library Cochrane, Clinical Trials, Proquest and PubMed. Adults over 18 years of age with any nutritional status were studied. The intervention corresponded to intermittent fasting of at least 16 hours. Risk of bias were assessed according to the Cochrane collaboration. Results: Six clinical trials were analyzed, finding that the ADA protocol, present in four of them, generated changes in the variables: triglycerides, c-HDL, c-LDL, total cholesterol, weight, lean mass, fat mass and systolic blood pressure, while the ART protocol, present in the remaining two, caused changes in the variables: weight, fat mass, lean mass, triglycerides, total cholesterol, c-LDL, c-HDL and glycemia. Conclusion: The available evidence with clinical trials allows us to suggest that the ADA and ART protocols can be an alternative diet for adults. However, caloric adjustment and adequate education on healthy lifestyles show similar results. Notwithstanding this, intermittent fasting may be an alternative for those who find it difficult to follow a dietary pattern with daily caloric restriction.