Proyectos

Adipose tissue expansion associated with obesity drives to a chronic low-grade inflammation state that alters metabolically relevant tissues, predisposing to developing metabolic diseases. This sustained inflammation causes alteration in SkM glucose uptake, impairs protein metabolism and causes mitochondrial dysfunction. Skeletal muscle (SkM) is a relevant organ responsible for whole-body metabolism and homeostasis. It has been recently proposed that obesity causes a phenomenon known as "anabolic resistance," where Skm cannot respond to anabolic stimuli induced by a nutritional challenge and muscle contraction and where inflammation could be a relevant mediator. The inflammatory response is regulated by the priming and activation of the NLRP3 inflammasome. However, the response to the NLRP3 inflammasome in human skeletal muscle (Hskm) has not been described, nor their possible relation with protein metabolism. Nowadays, the ketone body β-hydroxybutyrate (βHB) produced on liver mitochondria under ketogenic diets, caloric restriction or ingested exogenously as a supplement, has emerged as a possible muscle-sparing molecule. Still, the mechanism by which βHB could benefit protein metabolism or mitochondrial function is not understood. Interestingly, it has been shown that βHB by itself is a selective inhibitor of the NLRP3 inflammasome on human monocytes, suggesting an important role in controlling the inflammation response. Nevertheless, the anti-inflammatory role of βHB has not been tested on Hskm, neither the modulation of NLRP3 inflammasome nor their possible role in restoring anabolic resistance. To evaluate the effects of β- hydroxybutyrate supplementation on the anabolic response, NRLP3 inflammasome activation and mitochondrial dysfunction in skeletal muscle from obese individuals. Aim 1.- To determine the acute response of βHB supplementation on skeletal muscle inflammation, protein synthesis, and mitochondrial function in obese individuals. 15 lean and 15 obese men and women will be submitted to an acute protein intake (Whey protein 25g) with or without the previous ingestion of a Ketone Monoester (470 mg/kg)(Kme, ΔG®) in a cross-over protocol. Basal and postprandial (MPS) will be assessed in Vastus Lateralis (VL) muscle biopsy obtained at basal (0), 2, and after 4 hours of each condition respectively and determined afterward by LC-MS/MS. Plasma inflammation markers will be determined by ELISA while protein levels of mTOR signaling (pmTOR, 4EB-BP1, p70S6K and NLRP3 components) by immunoblot. Also, we will determine Hskm mitochondrial oxygen consumption and hydrogen peroxide (H2O2) as markers of mitochondrial function. Expected result: We expect that βHB supplementation causes a sensitizing effect on protein synthesis on obese Skm samples, a decrease in plasma and Skm inflammation markers, decrease or inactivation of the NLRP3 inflammasome along with restoration of mitochondrial function. Aim 2.- To analyze the chronic effects of βHB intake on the anabolic resistance response and its association with NRLP3 inactivation and skeletal muscle function in obese individuals. To determine the chronic effects of βHB supplementation anabolic resistance, individuals will be submitted to a three times per day βHB intake (357mg/kg)(Kme, ΔG®) or placebo for 2-weeks. Continuous Glucose Monitors will be placed on each participant's arm to determine day-to-day glucose control and three times a day determination of capillary βHB. At the end of the second week, obese individuals will be submitted to an acute protein intake and VL muscle biopsy at basal (0), 2, and after 4 hours of each condition to evaluate MPS. Physical fitness will be determined by total strength, power and maximal oxygen consumption. Skm and plasma inflammation will be determined by immunoblot (mTOR, pmTOR, 4EB-BP1, p70S6K, NLRP3, Casp-1, IL-1β, IL-18) and ELISA, respectively. In contrast, Skm mitochondrial oxygen consumption and H2O2 will be assessed to determine mitochondrial function. Expected result: we expected that obese individuals that are supplemented chronically with βHB will have an increased response to a whey protein leucine-enriched challenge reflected on the increase of MPS related to NLRP3 attenuation mitochondrial function restoration. Aim 3.- To determine the connection between the NLRP3 inactivation, mitochondrial function, and the attenuation of skeletal muscle anabolic resistance induced by βHB treatment in vitro. Primary human skeletal muscle (Hskm) from obese and lean donors obtained in biopsies from aim 1 will be stimulated with ATP (5mM), LPS (1μg/ml), ATP+LPS within the presence or absence of different concentration of βHB (0,5-5mM) and submitted to a leucine challenge (1.5mM), oxygen consumption and H2O2 determination. To test cause-effect Hskm will be transfected with a control or an NLRP3-pooled specific siRNA and submitted to leucine challenge. Here, p70S6K, p70S6K p-4EBP1, 4EBP1, mTOR, p-mTOR, NLRP3, Casp-1, IL-1β, IL-18 and Puromycin incorporation will be measured by immunoblot to test anabolic resistance. Expected result: We expected that βHB decreases NLRP3 inflammasome while increasing protein synthesis on Hskm of obese individuals, associated with Hskm myotube diameter. Thus, we propose a novel exogenous βHB intake approach to improve muscle function in obese populations by reducing systemic and Hskm inflammation, restoring skeletal muscle protein metabolism mediated by NLRP3 attenuation and improving mitochondrial function

El proyecto tiene como propósito abordar, a través de un análisis situado y contextual de cuatro regiones del país, diversas instancias involucradas en el ejercicio de los derechos sexuales y reproductivos de las mujeres con discapacidad que habitan en contextos rurales, desde un enfoque inclusivo y de género junto a las implicancias psicosociales derivadas de ello.

Antimicrobial resistance is a global phenomenon aggravated in recent decades by the inappropriate use of antimicrobials in human and veterinary medicine, the lack of prevention and control measures for infections associated with health care, and the limited development of new antimicrobials. It causes an increase in mortality, morbidity, and health spending. In this sense, the irrational use of antimicrobials in food-producing animals can reduce the effectiveness of those antibiotics in treating animal and human diseases. It also represents an additional risk for antimicrobial resistance by transferring antibiotics to food for human consumption and generating a new source of exposure. The residual antibiotics in food have been related to some adverse effects on human health, including allergic reactions, disruption of digestive system function, and chronic toxic effects from prolonged low-level exposure. It also represents a risk for the animals by jeopardizing the effectiveness of the necessary treatments. Considering that, the project seeks to generate evidence regarding progress at the local level in regulatory issues and regarding the presence of antibiotics in food to raise awareness about the proper use of antibiotics in animals and humans and promote good practices

Water is an irreplaceable resource for developing socioeconomic activities and maintaining life on the planet. According to projections, water scarcity will increase, especially in those countries vulnerable to the effects of climate change and accelerated population growth. The negative impacts of the water deficit are already visible in some regions of the planet. Through the ECOH-WATER project, we will develop capacities for the access and use of rainwater in educational centers in Guatemala and Bolivia for sustainable consumption, adapting to the impacts generated by climate change through strategies based on local needs. To do this, we will first diagnose the areas at risk of drought using Geographic Information Systems (GIS) to prioritize interventions. In the selected areas, we will develop an Action Research study with a strong participatory component to involve communities in implementing a rainwater harvesting system. Additionally, we will implement educational strategies for developing skills in seeking rational and sustainable water use. The project will establish alliances with local actors for the project's sustainability. The search for strategies to access quality water for human, animal, and environmental consumption is a worldwide priority. It must involve the communities, raise awareness about natural resources and risk behaviors, and work collaboratively with decision-makers. On the other hand, the transdisciplinary work proposed in this project will allow the search for solutions with an integral vision. On the other hand, this project highlights the south-south collaboration to generate learning, enhance local resources, and move toward our region's sustainable development.

Centro que se enfocará en el desarrollo de estudios farmacológicos orientados a combatir diversas enfermedades neurodegenerativas

Experiencias del Movimiento Social de la Discapacidad en América Latina: Itinerarios de lucha por los derechos del Colectivo Nacional por la Discapacidad de Chile y la Asociación de Discapacidad del Guayas de Ecuador.

Fortalecer la red comunitaria de apoyo para las personas en situación de discapacidad en la región de O'Higgins a través de la generación de conocimiento, el perfeccionamiento profesional y aplicación de metodología A+S en CCR y otros organismos pertinentes de la región.

Desarrollar y validar mediante ensayos in vivo un gel energético para deportistas de alto rendimiento, formulado en base a miel y extractos naturales, para ser utilizado como potenciador del rendimiento deportivo y la recuperación muscular post ejercicio. Los principales objetivos son: 1) Formular el gel energético en base a los requerimientos nutricionales especí􀃕cos de deportistas de alto rendimiento, caracterizándolo en términos nutricionales, capacidad antioxidante y ausencia de sustancias no deseadas. 2)Evaluar la tolerabilidad in vivo del producto en términos de palatabilidad y efectos gastrointestinales. 3)Diseñar e implementar el proceso mezclamiento y envasado para escalar la producción. 4)Cuanti􀃕car los efectos del producto desarrollado respecto del aporte sobre el rendimiento deportivo, la recuperación muscular post ejercicio y síntomas de malestar gastrointestinal. y 5) Fortalecer el modelo de negocios.

Desarrollar y validar mediante ensayos in vivo un gel energético para deportistas de alto rendimiento, formulado en base a miel y extractos naturales, para ser utilizado como potenciador del rendimiento deportivo y la recuperación muscular post ejercicio. Los principales objetivos son: 1) Formular el gel energético en base a los requerimientos nutricionales especí􀃕cos de deportistas de alto rendimiento, caracterizándolo en términos nutricionales, capacidad antioxidante y ausencia de sustancias no deseadas. 2)Evaluar la tolerabilidad in vivo del producto en términos de palatabilidad y efectos gastrointestinales. 3)Diseñar e implementar el proceso mezclamiento y envasado para escalar la producción. 4)Cuanti􀃕car los efectos del producto desarrollado respecto del aporte sobre el rendimiento deportivo, la recuperación muscular post ejercicio y síntomas de malestar gastrointestinal. y 5) Fortalecer el modelo de negocios.

Desarrollar y validar mediante ensayos in vivo un gel energético para deportistas de alto rendimiento, formulado en base a miel y extractos naturales, para ser utilizado como potenciador del rendimiento deportivo y la recuperación muscular post ejercicio. Los principales objetivos son: 1) Formular el gel energético en base a los requerimientos nutricionales especí􀃕cos de deportistas de alto rendimiento, caracterizándolo en términos nutricionales, capacidad antioxidante y ausencia de sustancias no deseadas. 2)Evaluar la tolerabilidad in vivo del producto en términos de palatabilidad y efectos gastrointestinales. 3)Diseñar e implementar el proceso mezclamiento y envasado para escalar la producción. 4)Cuanti􀃕car los efectos del producto desarrollado respecto del aporte sobre el rendimiento deportivo, la recuperación muscular post ejercicio y síntomas de malestar gastrointestinal. y 5) Fortalecer el modelo de negocios.