Development of properly-polarized trophoblast stem cell-derived organoids to model early human pregnancy.

The development of human trophoblast stem cells (hTSC) and stem cell-derived trophoblast organoids has enabled investigation of placental physiology and disease and early maternal-fetal interactions during a stage of human pregnancy that previously had been severely restricted. A key shortcoming in existing trophoblast organoid methodologies is the non-physiologic position of the syncytiotrophoblast (STB) within the inner portion of the organoid, which neither recapitulates placental villous morphology in vivo nor allows for facile modeling of STB exposure to the endometrium or the contents of the intervillous space. Here we have successfully established properly-polarized human trophoblast stem cell (hTSC)-sourced organoids with STB forming on the surface of the organoid. These organoids can also be induced to give rise to the extravillous trophoblast (EVT) lineage with HLA-G + migratory cells that invade into an extracellular matrix-based hydrogel. Compared to previous hTSC organoid methods, organoids created by this method more closely mimic the architecture of the developing human placenta and provide a novel platform to study normal and abnormal human placental development and to model exposures to pharmaceuticals, pathogens and environmental insults. Motivation: Human placental organoids have been generated to mimic physiological cell-cell interactions. However, those published models derived from human trophoblast stem cells (hTSCs) or placental villi display a non-physiologic "inside-out" morphology. In vivo , the placental villi have an outer layer of syncytialized cells that are in direct contact with maternal blood, acting as a conduit for gas and nutrient exchange, and an inner layer of progenitor, single cytotrophoblast cells that fuse to create the syncytiotrophoblast layer. Existing "inside-out" models put the cytotrophoblast cells in contact with culture media and substrate, making physiologic interactions between syncytiotrophoblast and other cells/tissues and normal and pathogenic exposures coming from maternal blood difficult to model. The goal of this study was to develop an hTSC-derived 3-D human trophoblast organoid model that positions the syncytiotrophoblast layer on the outside of the multicellular organoid.

Tumorigenic effect mediated by ROS/eicosanoids and their regulation on TP53 expression in a murine mammary gland adenocarcinoma.

The aim of this study was to investigate the in vivo and in vitro effects of dietary ω-6 and ω-3 polyunsaturated fatty acids (PUFAs) and their derivatives on the expression of TP53 and their relationship with cellular proliferation and death in a murine mammary adenocarcinoma model. BALB/c mice were divided in three diet groups: chia oil (ChO) rich in ω-3, corn oil (CO) rich in ω-6/ω-3 and safflower oil (SO) rich in ω-6 and subcutaneously inoculated with LMM3 mammary tumor cell line. Results demonstrated that diets with higher concentration of omega-6 PUFAs induced an increment of linoleic and arachidonic acid on tumor cell membranes increasing ROS liberation, 12(S)-HHT generation, TP53, Ki67 expression and cell proliferation. However, diets enriched with high content in omega-3 PUFAs induced higher tumor cell apoptosis and tumor infiltration of CD3+ lymphocytes, lowest cell viability and proliferation. Dietary omega-3 PUFAs nutritional intervention can be used as a potential preventative strategy to inhibit the molecular signaling pathways involved in the mammary tumor growth process as the TP53.

A case-control study: Evaluating the role of leukotriene receptor antagonists in preventing the cardiovascular and cerebrovascular disease.

INTRODUCTION: Leukotriene receptor antagonists (LTRAs) are used as a therapeutic alternative in asthmatic patients. Different animal studies indicate that LTRAs can decrease intimal hyperplasia after vascular injury, and have a protective role in cerebral ischemia. OBJECTIVE: The aim of this study was to assess the role of leukotriene receptor antagonists in preventing the cardiovascular and ischemic stroke in humans. MATERIAL AND METHOD: A matched case-control study with a follow up period of three years has been conducted, investigating the effect of the LTRAs in the myocardial infarct (MI) risk, and in the ischemic stroke (IS) risk in asthmatic patients from San Cecilio University Hospital of Granada, and from two Primary Health Care Centers of Granada. RESULTS: 59 cases with MI and 108 cases with IS were included in the study, each of them with an equal number of controls matched by age and sex in each of the two Health Care Centers. Unlike for MI risk, the treatment with LTRAs was associated with a slight trend in reducing the risk of stroke, in both of the primary care controls (Odds ratios: 0.74 (0.37-1.47); 0.82 (0.4-1.67), for the first, and the second Health Centers Controls, respectively), but without reaching a statistical significance. CONCLUSIONS: The results did not confirm a protective effect of LTRAs on cardiovascular risk as suggested by different animal studies.

Nutritional chemoprevention of urinary tract tumors (UTT) induced by lithogenic agents: risk for UTT in children exposed to melamine-contaminated milk formulas.

Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.

Educación alimentaria-nutricional (EAN) en la enseñanza primaria municipal de Córdoba: una experiencia en investigación-acción participativa (IAP): año 2008 / Nutrition education in municipal primary schools in Córdoba: an experience in participatory action research (par) in 2008

La EAN ha sido reconocida como la mejor estrategia para el control y prevención de problemas relacionados con la alimentación. Sin embargo aún no ha sido incorporada sistemáticamente en las escuelas argentinas. El objetivo de este trabajo fue analizar los hábitos alimentarios de los alumnos, la tarea pedagógica de docentes y la EAN en la enseñanza primaria en el marco de un estudio de investigación acción participativa (IAP) para luego implementar conjuntamente con la población involucrada la intervención educativa correspondiente. Se usaron para la recolección de datos y su triangulación: entrevista semiestructurada, grupos focales, observación directa y análisis de contenido. Para la intervención educativa se recurrió al Modelo Comunitario sustentado en metodologías Constructivistas. En este marco, se llevaron a cabo cinco talleres educativos y dos tutorías con los docentes, sobre contenidos de Alimentación Saludable y su inclusión en la propuesta didáctica como contenidos transversales. El impacto de la intervención pudo ser valorado positivamente ya que los docentes diseñaron un proyecto sobre Alimentación y Nutrición que forma parte del Proyecto Educativo Institucional de la escuela y que involucra también al quiosco escolar y a la población de padres de los escolares y el material didáctico diseñado y validado para dicha población, lo cual contribuye a mejorar la calidad de la intervención para promover hábitos alimentarios saludables y duradeos.