Proyectos

URO 2295. El Ministerio de Educación a través del Departamento de Fortalecimiento Institucional de la Subsecretaria de Educación Superior financia proyectos que permitan contribuir al desarrollo social y territorial, a nivel local y/o regional, a través de la generación compartida de conocimientos, oportunidades de desarrollo y/o beneficios entre las instituciones de educación superior y los actores sociales, tanto públicos como privados. En este contexto, este proyecto busca generar estrategias eficaces – con la comunidad y distintos actores sociales de la región – y basadas en la evidencia que aborden el aumento de la prevalencia de enfermedades crónicas no transmisibles a través de la mejora de los patrones de actividad física y alimentarios de la población regional. Objetivo general: Fortalecer las estrategias comunitarias de promoción de la salud, prevención y tratamiento temprano y oportuno de enfermedades crónicas no transmisibles en la Región de O’Higgins con foco en actividad física y nutrición saludable

Proyecto financiación PICTO-2022- GENERO00045. El equipo de investigación integra las disciplinas en aspectos jurídicos y de derechos humanos, salud mental, medicina, sociología, estadísticas y especialistas en desarrollo local; ciencias políticas, justicia de género y planificación estratégica con enfoque de género. Es un equipo interdisciplinar y contribuye al campo de los cuidados, en la incorporación del enfoque de género; desarrollo territorial y derechos.

URO 2295. El Ministerio de Educación a través del Departamento de Fortalecimiento Institucional de la Subsecretaria de Educación Superior financia proyectos que permitan contribuir al desarrollo social y territorial, a nivel local y/o regional, a través de la generación compartida de conocimientos, oportunidades de desarrollo y/o beneficios entre las instituciones de educación superior y los actores sociales, tanto públicos como privados. En este contexto, este proyecto busca generar estrategias eficaces – con la comunidad y distintos actores sociales de la región – y basadas en la evidencia que aborden el aumento de la prevalencia de enfermedades crónicas no transmisibles a través de la mejora de los patrones de actividad física y alimentarios de la población regional. Objetivo general: Fortalecer las estrategias comunitarias de promoción de la salud, prevención y tratamiento temprano y oportuno de enfermedades crónicas no transmisibles en la Región de O’Higgins con foco en actividad física y nutrición saludable

URO 2295. El Ministerio de Educación a través del Departamento de Fortalecimiento Institucional de la Subsecretaria de Educación Superior financia proyectos que permitan contribuir al desarrollo social y territorial, a nivel local y/o regional, a través de la generación compartida de conocimientos, oportunidades de desarrollo y/o beneficios entre las instituciones de educación superior y los actores sociales, tanto públicos como privados. En este contexto, este proyecto busca generar estrategias eficaces – con la comunidad y distintos actores sociales de la región – y basadas en la evidencia que aborden el aumento de la prevalencia de enfermedades crónicas no transmisibles a través de la mejora de los patrones de actividad física y alimentarios de la población regional. Objetivo general: Fortalecer las estrategias comunitarias de promoción de la salud, prevención y tratamiento temprano y oportuno de enfermedades crónicas no transmisibles en la Región de O’Higgins con foco en actividad física y nutrición saludable

URO 2295. El Ministerio de Educación a través del Departamento de Fortalecimiento Institucional de la Subsecretaria de Educación Superior financia proyectos que permitan contribuir al desarrollo social y territorial, a nivel local y/o regional, a través de la generación compartida de conocimientos, oportunidades de desarrollo y/o beneficios entre las instituciones de educación superior y los actores sociales, tanto públicos como privados. En este contexto, este proyecto busca generar estrategias eficaces – con la comunidad y distintos actores sociales de la región – y basadas en la evidencia que aborden el aumento de la prevalencia de enfermedades crónicas no transmisibles a través de la mejora de los patrones de actividad física y alimentarios de la población regional. Objetivo general: Fortalecer las estrategias comunitarias de promoción de la salud, prevención y tratamiento temprano y oportuno de enfermedades crónicas no transmisibles en la Región de O’Higgins con foco en actividad física y nutrición saludable

URO 2295. El Ministerio de Educación a través del Departamento de Fortalecimiento Institucional de la Subsecretaria de Educación Superior financia proyectos que permitan contribuir al desarrollo social y territorial, a nivel local y/o regional, a través de la generación compartida de conocimientos, oportunidades de desarrollo y/o beneficios entre las instituciones de educación superior y los actores sociales, tanto públicos como privados. En este contexto, este proyecto busca generar estrategias eficaces – con la comunidad y distintos actores sociales de la región – y basadas en la evidencia que aborden el aumento de la prevalencia de enfermedades crónicas no transmisibles a través de la mejora de los patrones de actividad física y alimentarios de la población regional. Objetivo general: Fortalecer las estrategias comunitarias de promoción de la salud, prevención y tratamiento temprano y oportuno de enfermedades crónicas no transmisibles en la Región de O’Higgins con foco en actividad física y nutrición saludable

During the last decades, compelling evidence shows how the context in which early life takes place impinges risk or protection for later development of non-communicable chronic diseases. In this regard, impaired fetal growth, as occur in the fetal growth restriction (FGR), leads to a higher risk for later cardiovascular diseases, an effect that would be mediated by accelerated aging at molecular, structural, and functional levels. FGR remains a leading cause of perinatal morbidity and mortality, affecting ~10% of pregnancies, but ranging from 5 to 25% depending on the population surveyed, with a higher prevalence among pregnant women of low socioeconomic status. In the clinic, FGR is normally defined by a fetal weight below the 10th percentile, however, new evidence shows that impaired intrauterine growth may affect several neonates born over the 10th percentile, especially late in pregnancy, which may be missed from the perinatal survey for preventing adverse outcomes. This points out the need for further studies to improve the understanding and identification of altered fetal growth trajectories and their consequences on vascular function. Studies in the placenta show that FGR vascular dysfunction is also found at birth in chorionic and umbilical arteries. We have demonstrated the presence of functional and molecular markers (e.g. vasodilator mediators and epigenetic changes) of endothelial dysfunction in human FGR umbilical and chorionic vessels, findings that have been further confirmed by comparing systemic and umbilical arteries in guinea pigs and chicken FGR models. These traits suggest that umbilical artery endothelial cells (HUAEC), in complement with approaches in animal models, can be used as a surrogate to explore the vascular programming within the fetus, however, their translation to clinical preventive applications for promoting healthy aging deserves further studies. It worth noting that fetal reduced oxygen supply (fetal hypoxia) and altered blood flow patterns (e.g. shear stress) are key clinical markers in the FGR, independently of the constraints leading to impaired growth, and both factors exert a tight control of vascular development and function across life. However, how these key stimuli interact and impose an epigenetic program on the endothelial function remains elusive. This proposal will focus on the crosstalk between hypoxia and shear stress that results in the endothelial programming related to impaired fetal growth, and the molecular mechanisms that mediate the vascular responses to these stimuli. Furthermore, we will address if these molecular markers may allow detecting early vascular aging in FGR subjects beyond the 10th centile cutoff. We hypothesize that “Impaired fetal growth conditions are associated with epigenetic programming of aging- and mechanosensing-related miRNAs and transcripts in the endothelium, which can be triggered by the confluence of altered flow patterns and hypoxia resulting in molecular and structural pro-hypertensive biomechanical vascular properties”. This hypothesis will be addressed by three General Objectives (GO) involving ex vivo, in vitro, and in vivo observational and mechanistic approaches: GO1 To demonstrate, in HUAEC, whether late FGR results in epigenetic changes related to the regulation of vascular aging and the expression of mechanosensing mechanisms involved in the endothelial-dependent relaxation, and their relationship with general prenatal parameters of vascular health. GO1 will be performed by recruiting HUAEC samples from late FGR and control pregnancies, to assess transcriptomic and DNA methylation analyses that will be crossed with prenatal clinical data. GO2 To study, in vivo, whether hypoxia and shear stress differentially regulate mechanosensing pathways involved in the endothelial-dependent relaxation and their relationship with the in vivo and ex vivo vascular properties (e.g. functional and biomechanical). GO2 will be performed in chicken embryos exposed to hypoxia and treated with agents targeting mechanosensing pathways, in which wall shear stress will be determined by Ultrasound Localization Microscopy, with complementary functional, structural, and molecular analyses. GO 3. To study, in cultured HUAEC, whether stimuli related to impaired fetal growth converge in the regulation of mechanosensing- and aging-related transcripts and miRNA, contributing to the cellular programming of endothelial dysfunction. GO3 will be performed in HUAEC exposed, in vitro, to sustained hypoxia and diverse flow patterns (shear stress), in which target DNA methylation, miRNA, transcripts, and proteins will be assessed. Our expected outcome is to improve the knowledge about the endothelial epigenetic programming after FGR in humans and enhance the characterization of the shear stress patterns and mechanisms associated with chronic fetal hypoxia. These effects will be isolated by studying, in vivo, hypoxic chicken embryos and, in vitro, cultured HUAEC exposed to FGR-like flow patterns. 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 preventing, diagnosing, and treating FGR-pregnancies.

During the last decades, compelling evidence shows how the context in which early life takes place impinges risk or protection for later development of non-communicable chronic diseases. In this regard, impaired fetal growth, as occur in the fetal growth restriction (FGR), leads to a higher risk for later cardiovascular diseases, an effect that would be mediated by accelerated aging at molecular, structural, and functional levels. FGR remains a leading cause of perinatal morbidity and mortality, affecting ~10% of pregnancies, but ranging from 5 to 25% depending on the population surveyed, with a higher prevalence among pregnant women of low socioeconomic status. In the clinic, FGR is normally defined by a fetal weight below the 10th percentile, however, new evidence shows that impaired intrauterine growth may affect several neonates born over the 10th percentile, especially late in pregnancy, which may be missed from the perinatal survey for preventing adverse outcomes. This points out the need for further studies to improve the understanding and identification of altered fetal growth trajectories and their consequences on vascular function. Studies in the placenta show that FGR vascular dysfunction is also found at birth in chorionic and umbilical arteries. We have demonstrated the presence of functional and molecular markers (e.g. vasodilator mediators and epigenetic changes) of endothelial dysfunction in human FGR umbilical and chorionic vessels, findings that have been further confirmed by comparing systemic and umbilical arteries in guinea pigs and chicken FGR models. These traits suggest that umbilical artery endothelial cells (HUAEC), in complement with approaches in animal models, can be used as a surrogate to explore the vascular programming within the fetus, however, their translation to clinical preventive applications for promoting healthy aging deserves further studies. It worth noting that fetal reduced oxygen supply (fetal hypoxia) and altered blood flow patterns (e.g. shear stress) are key clinical markers in the FGR, independently of the constraints leading to impaired growth, and both factors exert a tight control of vascular development and function across life. However, how these key stimuli interact and impose an epigenetic program on the endothelial function remains elusive. This proposal will focus on the crosstalk between hypoxia and shear stress that results in the endothelial programming related to impaired fetal growth, and the molecular mechanisms that mediate the vascular responses to these stimuli. Furthermore, we will address if these molecular markers may allow detecting early vascular aging in FGR subjects beyond the 10th centile cutoff. We hypothesize that “Impaired fetal growth conditions are associated with epigenetic programming of aging- and mechanosensing-related miRNAs and transcripts in the endothelium, which can be triggered by the confluence of altered flow patterns and hypoxia resulting in molecular and structural pro-hypertensive biomechanical vascular properties”. This hypothesis will be addressed by three General Objectives (GO) involving ex vivo, in vitro, and in vivo observational and mechanistic approaches: GO1 To demonstrate, in HUAEC, whether late FGR results in epigenetic changes related to the regulation of vascular aging and the expression of mechanosensing mechanisms involved in the endothelial-dependent relaxation, and their relationship with general prenatal parameters of vascular health. GO1 will be performed by recruiting HUAEC samples from late FGR and control pregnancies, to assess transcriptomic and DNA methylation analyses that will be crossed with prenatal clinical data. GO2 To study, in vivo, whether hypoxia and shear stress differentially regulate mechanosensing pathways involved in the endothelial-dependent relaxation and their relationship with the in vivo and ex vivo vascular properties (e.g. functional and biomechanical). GO2 will be performed in chicken embryos exposed to hypoxia and treated with agents targeting mechanosensing pathways, in which wall shear stress will be determined by Ultrasound Localization Microscopy, with complementary functional, structural, and molecular analyses. GO 3. To study, in cultured HUAEC, whether stimuli related to impaired fetal growth converge in the regulation of mechanosensing- and aging-related transcripts and miRNA, contributing to the cellular programming of endothelial dysfunction. GO3 will be performed in HUAEC exposed, in vitro, to sustained hypoxia and diverse flow patterns (shear stress), in which target DNA methylation, miRNA, transcripts, and proteins will be assessed. Our expected outcome is to improve the knowledge about the endothelial epigenetic programming after FGR in humans and enhance the characterization of the shear stress patterns and mechanisms associated with chronic fetal hypoxia. These effects will be isolated by studying, in vivo, hypoxic chicken embryos and, in vitro, cultured HUAEC exposed to FGR-like flow patterns. 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 preventing, diagnosing, and treating FGR-pregnancies.

Proyecto que busca determinar mecanismos moleculares de como los ácidos grasos omega-3 y el ejercicio físico pueden mejorar la calidad de vida, funcionalidad y parámetros de inflamación de pacientes con artritis reumatoide.

EFECTO DE LA OBESIDAD INDUCIDA POR EL CONSUMO DE UNA DIETA ALTA EN GRASAS SOBRE LA ACTIVACIÓN DEL INFLAMASOMA NLRP3 EN LA CÓCLEA Y LA FUNCIÓN DEL SISTEMA AUDITIVO