Proyectos

Objetivo de la investigación: Evaluar el efecto de un extracto hidroalcohólico de Lampaya sobre la alteración en la vía de señalización de la insulina inducida por ácido palmítico adipocitos 3T3-L1.

Adverse intrauterine conditions, such as fetal growth restriction (FGR), increase the risk to develop cardiometabolic diseases in the adulthood. This concept has been called ‘Developmental Origins of Health and Disease’ (DOHaD) and relies on the activation of mechanisms sensing and signaling a diversity of stimuli during early development that later leads to higher risk of disease. The mechanisms that have been broadly suggested to be involved in these processes are epigenetic modifications in key gene promoters that could ‘record’ normal and abnormal perinatal stimuli. Intrauterine oxidative stress and chronic hypoxia are common features in FGR. Several cellular processes require the participation of pro-oxidant molecules which are normally neutralized by antioxidant defenses. However, under determined conditions, such as chronic hypoxia, the pro-oxidants overcome these defenses inducing oxidative stress. The latter is an important stimulus that regulates vascular function and cardiovascular physiology, playing a key role in the development of cardiovascular diseases, regulating negatively the bioavailability of the main vasodilator nitric oxide (NO). In addition, the vascular system presents a high phenotypic plasticity during life, which is modulated and restricted by epigenetic mechanisms (including DNA methylation, histone post-translational modifications, and micro RNAs). The higher cardiovascular risk in adults born with FGR can be traced back to a reduced arterial compliance in pre-pubertal subjects and a decreased peripheral endothelial-dependent vascular relaxation at birth. This endothelial dysfunction (ED) is also observed in FGR placental vessels, suggesting an early onset of ED that could be evidenced in systemic and placental arteries. Our studies in human placentae have demonstrated that ED in FGR can be modulated by oxidative stress and is associated with changes in proteome profile as well as an epigenetic-mediated regulation of eNOS expression. Similarly, in guinea pigs, we have found that ED in FGR is also occurring in the fetal arteries and is prevented by maternal treatment with antioxidants. Analysis of eNOS expression and Nos3 promoter DNA methylation profile in endothelial cells from the aorta and umbilical arteries of FGR guinea pigs shows common molecular markers of ED in FGR systemic and umbilical vessels which are reverted by a maternal antioxidant treatment. Altogether, these data support the role of oxidative stress in the epigenetic programming of ED in FGR and the potential predictive value of studying human umbilical arteries endothelial cells (HUAEC). However, there are no studies addressing the time course and origins of the ED in FGR and the participation of additional epigenetic mechanisms, such as miRNAs, in this process. Here, we put forward two inter-related hypotheses. First, that arterial endothelium from babies with FGR show a genomic DNA methylation signature along with an altered expression of miRNAs miR-21, miR-126 & miR-155, which contributes to changes in the expression of enzymes related to NO synthesis, endothelial dysfunction, and vascular remodeling. Second, that FGR has, during gestation, dynamic changes in the expression of miRNAs miR-21, miR-126 & miR-155 as an early response to hypoxia and oxidative stress in the fetus leading, in the long term, to endothelial dysfunction and vascular remodeling. These hypothesis will be tested in primary cultures of HUAEC from FGR neonates and validated using guinea pig and chick embryo models of FGR according to the following general aims (GA): GA-1 To demonstrate, in human umbilical artery endothelial cells, whether FGR is associated with an altered epigenetic regulation (i.e. increased levels of miR-21, miR-126 & miR-155 and a differential genomic DNA methylation) of NO-related enzymes (i.e. eNOS, DDAH1, Nrf2, Arg2, and HO-1), which modifies the response to hypoxia and impairs angiogenic capacity.GA-2 To demonstrate, in FGR guinea pigs, whether circulating levels of miR-21, miR-126 & miR-155 are dynamically regulated during the development of fetal vascular dysfunction and if the prevention of oxidative stress by an antioxidant administration to mothers, contributes to this regulation. GA-3 To demonstrate, in FGR chicken embryos, whether the silencing of miR-21, miR-126 and miR-155 expression modifies the endothelial and vascular dysfunction induced by chronic hypoxia and oxidative stress. Our expected outcome is to demonstrate that miRNAs miR-21, miR-126 & miR-155 participates in the early defense to hypoxia and oxidative stress in the FGR, but leading at long-term to ED. Further, we propose that regulation of these miRNAs during gestation could prevent these effects. This project is not only relevant to uncover the developmental mechanisms that determine short- and long-term vascular dysfunction, but also to open potential approaches for treatments in complicated pregnancies in humans. Combined, our program of work offers insights into mechanisms underlying the association between intrauterine hypoxia, oxidative stress and the increased risk of developing cardiovascular disease in later life, and possible interventions considering administration of therapeutic agents at critical stages of intrauterine development.

La construcción de un modelo predictivo, que podría dar origen a una herramienta de screening para ayudar al profesor a identificar un problema de salud mental en el aula y solicitar ayuda a los equipos de apoyo psico-pedagógico dentro del establecimiento. De igual forma, este proyecto podría dar origen a una cohorte de estudiantes que permita profundizar en el estudio de la relación salud mental – resultados académicos, con productos científicos (conocimiento) y tecnológicos de innovación, que apoyen el trabajo de los docentes y sus establecimientos.

La construcción de un modelo predictivo, que podría dar origen a una herramienta de screening para ayudar al profesor a identificar un problema de salud mental en el aula y solicitar ayuda a los equipos de apoyo psico-pedagógico dentro del establecimiento. De igual forma, este proyecto podría dar origen a una cohorte de estudiantes que permita profundizar en el estudio de la relación salud mental – resultados académicos, con productos científicos (conocimiento) y tecnológicos de innovación, que apoyen el trabajo de los docentes y sus establecimientos.

La construcción de un modelo predictivo, que podría dar origen a una herramienta de screening para ayudar al profesor a identificar un problema de salud mental en el aula y solicitar ayuda a los equipos de apoyo psico-pedagógico dentro del establecimiento. De igual forma, este proyecto podría dar origen a una cohorte de estudiantes que permita profundizar en el estudio de la relación salud mental – resultados académicos, con productos científicos (conocimiento) y tecnológicos de innovación, que apoyen el trabajo de los docentes y sus establecimientos.

La Organización Mundial de la Salud en conjunto con Autism Speaks ha desarrollado el Programa de Formación a Cuidadores (CST) para niños y niñas con TD (OMS, 2018). Dicho proyecto se enmarca en las recomendaciones de la “Guía de Intervención mhGAP para los trastornos mentales, neurológicos y por uso de sustancias de OMS, la cual se implementa desde el año 2016 en la red de Atención Primaria de Salud de Chile, con un módulo específico de trastornos del desarrollo (OMS, 2010; MINSAL 2018). Objetivo general Evaluar aceptabilidad y factibilidad del pre-piloto CST implementado en la Comuna de Santiago Centro. Objetivos específicos 1. Analizar las medidas de evaluación aplicadas a través de la realización del programa. 2. Realizar entrevista a facilitadores y grupo focal a padres, una vez finalizado el programa. Estudio cuali-cuantitativo.

El objetivo principal del proyecto fue estudiar el efecto del Andrografolido sobre la inflamación en el contexto de la Enfermedad de Alzheimer

Estudio que involucra el estudio de la via Wnt en la regulación de vias metabolicas en el contexto de la Enfermedad de Alzheimer