Integrating the roles of liver x receptors in inflammation and infection: mechanisms and outcomes

Liver X receptors (LXRs) are transcription factors from the nuclear receptor family that can be pharmacologically activated by high-affinity agonists. LXR activation exerts a combination of metabolic and anti-inflammatory actions that result in the modulation of immune responses and in the amelioration of inflammatory disorders. In addition, LXR agonists modulate the metabolism of infected cells and limit the infectivity and/or growth of several pathogens. This review gives an overview of the recent advances in understanding the complexity of the mechanisms through which the LXR pathway controls inflammation and host-cell pathogen interaction

Mechanisms of LXR-mediated control of obesity-induced metaflammation and insulin-resistance

[eng] Obesity is nowadays considered a pandemic disease, and its incidence correlates with the concomitant increase of a set of associated comorbidities, including T2D, cardiovascular diseases, fatty liver disease, among others, which are all grouped within the metabolic syndrome. Insulin resistance is frequently developed in obesity and seems to be a common link to these associated diseases. Many efforts have focused in deciphering the mechanisms underlying insulin resistance, being metaflammation, that is the chronic low grade inflammatory response in the adipose tissue associated to obesity, the most well-documented. In this scenario, it is urgent to explore the relevance of anti-inflammatory actors as insulin-sensitizing agents. The nuclear receptors LXRs represent interesting therapeutic targets that can be pharmacologically activated by synthetic high affinity agonists. Accumulated evidence, including work from our group, indicates the importance of the LXR pathway in the negative control of inflammatory conditions. In this work we have focused in better understanding several aspects of LXR biology. On one side, using primary murine macrophages, our results suggest that negative crosstalk between LXRs and the pro- inflammatory transcription factor IRF1 occurs in a gene-specific manner during the macrophage response to IFN-!. Notably, IRF1 plays a fine-tuning role in the control of the expression of the LXR target CD38. On the other side, we have evaluated the consequences of LXR activation in a murine model of obesity-associated insulin resistance. Pharmacological administration of an LXR agonist resulted in decreased body weight and basal glycemia and in improved systemic insulin sensitivity in diet-induced obese mice. However, these effects did not correlate with broad inhibitory actions on metaflammation. Our results suggest that the insulin-sensitizing actions mediated by LXRs require functional systemic expression of the multi-functional protein CD38, but these effects do not depend on CD38 expression specifically in bone marrow-derived cells. In addition, our studies indicate that CD38-deficient mice are partially protected from both the increase in adiposity and the development of insulin resistance in response to a high fat diet, and this phenotype is not mediated by the lack of expression of CD38 in bone marrow-derived cells. In summary, this work unravels the importance of the multi-enzymatic protein CD38 in the insulin- sensitizing actions of the LXR pathway and opens the door to more precisely characterize the function of the LXR-CD38 axis specifically in metabolic cell compartments

El uso del etiquetado nutricional y su asociación con la adhesión a la dieta mediterránea y el estado nutricional determinado mediante la percepción de la imagen corporal en estudiantes universitarios de Valparaíso, Chile: un estudio transversal: Uso del etiquetado nutricional en universitarios

Introduction: The Mediterranean diet (DM) is recognized as a sustainable and healthy dietary pattern, however, the adherence of university students to its recommendations is low. Nutrition labelling is a strategy to promote healthy alimentary choices. The main purpose of this study was to analyze the association between the use of nutritional labelling, adherence to the MD the nutritional status determined through the perception of body image in Chilean university students. Methodology: A cross-sectional study was carried out in which 286 students between 18 and 29 years old participated, enrolled in a public university in Valparaíso, Chile. The adherence to the MD was determined by the KIDMED Test. The frequency of use of nutrition labelling was consulted through three questions: Do you check the number of "High in" labels on packaged foods before you buy them? Do you buy packaged foods with fewer "High In" labels to ensure a healthy choice? Do you read the nutrition labelling of packaged foods with “High In” labels before you buy them? In addition, the nutritional status was determined by the perception of body image. The application of the questionnaires was online. Logistic regression models were realized to evaluate the association between the variables. Results: About 55% reported a frequent use of nutrition labelling and 26,2% a high adherence to the MD and 51,4% had excess body weight (EBW). The students who frequently buy packaged foods with less “High In” labels and read the nutrition labelling before buy packaged foods had more likely of report a high adherence to the MD (OR:2,39; 95% IC: 1,17-4,85 y OR:2,38; 95% IC: 1,20-4,73 respectively) than those infrequent users of nutrition labelling (p<0,01). Conclusions: University students who frequently used nutrition labelling had a greater adherence to the MD compared to those infrequent users.Introducción: La dieta mediterránea (DM) es reconocida como un patrón dietético sostenible y saludable; sin embargo, la adhesión de los estudiantes universitarios a sus recomendaciones es baja. El etiquetado nutricional es una estrategia para promover elecciones alimentarias saludables. El objetivo de este estudio fue analizar la asociación entre el uso del etiquetado nutricional, la adhesión a la DM y el estado nutricional determinado mediante la percepción de la imagen corporal en estudiantes universitarios chilenos. Metodología: Se realizó un estudio transversal, en el que participaron 286 estudiantes entre 18 y 29 años, matriculados en una universidad pública de Valparaíso, Chile. La adhesión a la DM se determinó mediante el Test KIDMED, la frecuencia de uso del etiquetado nutricional se consultó utilizando tres preguntas: ¿revisas la cantidad de sellos “Alto en” de los alimentos envasados antes de comprarlos?; ¿compras alimentos envasados con menos sellos “Alto en” para asegurar una elección saludable?; ¿lees el etiquetado nutricional de los alimentos envasados con sellos “Alto en” antes de comprarlos?. El estado nutricional se determinó mediante la percepción de la imagen corporal. La aplicación de los cuestionarios fue en línea. Se realizaron Modelos de Regresión Logística para evaluar la asociación entre las variables. Resultados: Cerca del 55% reportó un uso frecuente del etiquetado nutricional, el 26,2% una alta adhesión a la DM y el 51,4% se percibe con exceso de peso corporal. Los estudiantes que frecuentemente compran alimentos envasados con menos sellos “Alto en” y leen el etiquetado nutricional antes de comprar alimentos envasados tuvieron más probabilidad de reportar una alta adhesión a la DM (OR:2,39;  IC 95%: 1,17-4,85 y OR:2,38; IC 95%: 1,20-4,73 respectivamente) que aquellos usuarios no frecuentes (p<0,01). Conclusiones: Los estudiantes universitarios que usaron frecuentemente el etiquetado nutricional tuvieron una mayor adhesión a la DM comparado con aquellos usuarios no frecuentes

El Uso del etiquetado nutricional y su asociación con la adhesión a la dieta mediterránea y el estado nutricional determinado mediante la percepción de la imagen corporal en estudiantes universitarios de Valparaíso, Chile: un estudio transversal: Uso del etiquetado nutricional en universitarios

Introduction: The Mediterranean diet (DM) is recognized as a sustainable and healthy dietary pattern, however, the adherence of university students to its recommendations is low. Nutrition labelling is a strategy to promote healthy alimentary choices. The main purpose of this study was to analyze the association between the use of nutritional labelling, adherence to the MD the nutritional status determined through the perception of body image in Chilean university students. Methodology: A cross-sectional study was carried out in which 286 students between 18 and 29 years old participated, enrolled in a public university in Valparaíso, Chile. The adherence to the MD was determined by the KIDMED Test. The frequency of use of nutrition labelling was consulted through three questions: Do you check the number of "High in" labels on packaged foods before you buy them? Do you buy packaged foods with fewer "High In" labels to ensure a healthy choice? Do you read the nutrition labelling of packaged foods with “High In” labels before you buy them? In addition, the nutritional status was determined by the perception of body image. The application of the questionnaires was online. Logistic regression models were realized to evaluate the association between the variables. Results: About 55% reported a frequent use of nutrition labelling and 26,2% a high adherence to the MD and 51,4% had excess body weight (EBW). The students who frequently buy packaged foods with less “High In” labels and read the nutrition labelling before buy packaged foods had more likely of report a high adherence to the MD (OR:2,39; 95% IC: 1,17-4,85 y OR:2,38; 95% IC: 1,20-4,73 respectively) than those infrequent users of nutrition labelling (p&lt;0,01). Conclusions: University students who frequently used nutrition labelling had a greater adherence to the MD compared to those infrequent users.Introducción: La dieta mediterránea (DM) es reconocida como un patrón dietético sostenible y saludable; sin embargo, la adhesión de los estudiantes universitarios a sus recomendaciones es baja. El etiquetado nutricional es una estrategia para promover elecciones alimentarias saludables. El objetivo de este estudio fue analizar la asociación entre el uso del etiquetado nutricional, la adhesión a la DM y el estado nutricional determinado mediante la percepción de la imagen corporal en estudiantes universitarios chilenos. Metodología: Se realizó un estudio transversal, en el que participaron 286 estudiantes entre 18 y 29 años, matriculados en una universidad pública de Valparaíso, Chile. La adhesión a la DM se determinó mediante el Test KIDMED, la frecuencia de uso del etiquetado nutricional se consultó utilizando tres preguntas: ¿revisas la cantidad de sellos “Alto en” de los alimentos envasados antes de comprarlos?; ¿compras alimentos envasados con menos sellos “Alto en” para asegurar una elección saludable?; ¿lees el etiquetado nutricional de los alimentos envasados con sellos “Alto en” antes de comprarlos?. El estado nutricional se determinó mediante la percepción de la imagen corporal. La aplicación de los cuestionarios fue en línea. Se realizaron Modelos de Regresión Logística para evaluar la asociación entre las variables. Resultados: Cerca del 55% reportó un uso frecuente del etiquetado nutricional, el 26,2% una alta adhesión a la DM y el 51,4% se percibe con exceso de peso corporal. Los estudiantes que frecuentemente compran alimentos envasados con menos sellos “Alto en” y leen el etiquetado nutricional antes de comprar alimentos envasados tuvieron más probabilidad de reportar una alta adhesión a la DM (OR:2,39;  IC 95%: 1,17-4,85 y OR:2,38; IC 95%: 1,20-4,73 respectivamente) que aquellos usuarios no frecuentes (p&lt;0,01). Conclusiones: Los estudiantes universitarios que usaron frecuentemente el etiquetado nutricional tuvieron una mayor adhesión a la DM comparado con aquellos usuarios no frecuentes

ROLE OF BIOCHEMICAL MARKERS IN THE MONITORING OF COVID-19 PATIENTS

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has given rise to a global sanitary emergency. The clinical characteristics of COVID-19 are varied and can range from an asymptomatic infection to a mild to severe pneumonia. Recent studies have shown that different laboratory parameters become altered in these patients, and as such are useful as biomarkers to assess the progression of the disease and categorize patients that may present a severe and/or fatal clinical condition. This review analyzes biochemical and immunological markers that become altered in COVID-19 patients and their impact on different organs at a hepatic, cardiac, renal and pancreatic level, as well as markers of inflammation, analyzing their implications in the evolution of the disease

La evaluación formativa en la enseñanza de historia, geografía y ciencias sociales

En nuestro sistema educativo la evaluación de los aprendizajes es una práctica centrada en resultados, y, por tanto, en su función social. Actualmente, el decreto 67/2018 plantea el desafío con una evaluación formativa que debe iniciar su implementación el año 2020. La investigación cualitativa basada en un estudio de casos múltiples, analiza cómo se implementa la evaluación formativa en la enseñanza primaria de Historia, Geografía y Ciencias Sociales, en colegios de la provincia de Talca. Los resultados confirman la presencia de una función pedagógica de la evaluación, condicionada por la estandarización del sistema educacional.In our educational system, the evaluation of learning is a practice focused on results, therefore, on its social function. Currently, the Decree 67/2018 poses the challenge with a formative evaluation that must begin its implementation in 2020. This qualitative research based on a multiple case study seeks to analyze how the formative evaluation is implemented at the teaching of History, Geography and Social Sciences, at schools in the province of Talca. The results indicate a pedagogical practice with the presence of the pedagogical function of evaluation, conditioned by the standardization of the educational system.Dans notre système éducatif, l'évaluation de l'apprentissage est une pratique centrée sur les résultats, et donc sur sa fonction sociale. Actuellement, le décret 67/2018 prévoit de relever le défi avec une évaluation formative qui doit commencer sa mise en oeuvre d'ici 2020. La présente recherche qualitative basée sur une étude de cas multiples cherche à analyser comment mettre en oeuvre l'évaluation formative dans l'histoire de l'histoire. , Géographie et sciences sociales, dans les collèges de la province de Talca. Les résultats indiquent une pratique pédagogique avec la présence d'une fonction d'évaluation pédagogique, conditionnée par la standardisation du système éducatif.Fil: Sánchez Sánchez, Gerardo. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Espinoza Cáceres, Thalía. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Gutiérrez Núñez, Nicole. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Letelier Contreras, Oliver. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Mora Vergara, Karenn. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Moraga Orellana, Romina. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; ChileFil: Muñoz Vega, Paulina. Universidad Católica del Maule. Facultad de Ciencias de la Educación. Maule; Chil

Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice

Altres ajuts: Fundació La Marató de TV3 2016 (303/C/2016) (201602.31) (to J.J.) and (97/C/2016) (201605-31) (to A.F.V.).The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: −44%; NAM HD: −57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation

Inhibition of the Hantavirus Fusion Process by Predicted Domain III and Stem Peptides from Glycoprotein Gc

Hantaviruses can cause hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome in humans. To enter cells, hantaviruses fuse their envelope membrane with host cell membranes. Previously, we have shown that the Gc envelope glycoprotein is the viral fusion protein sharing characteristics with class II fusion proteins. The ectodomain of class II fusion proteins is composed of three domains connected by a stem region to a transmembrane anchor in the viral envelope. These fusion proteins can be inhibited through exogenous fusion protein fragments spanning domain III (DIII) and the stem region. Such fragments are thought to interact with the core of the fusion protein trimer during the transition from its pre-fusion to its post-fusion conformation. Based on our previous homology model structure for Gc from Andes hantavirus (ANDV), here we predicted and generated recombinant DIII and stem peptides to test whether these fragments inhibit hantavirus membrane fusion and cell entry. Recombinant ANDV DIII was soluble, presented disulfide bridges and beta-sheet secondary structure, supporting the in silico model. Using DIII and the C-terminal part of the stem region, the infection of cells by ANDV was blocked up to 60% when fusion of ANDV occurred within the endosomal route, and up to 95% when fusion occurred with the plasma membrane. Furthermore, the fragments impaired ANDV glycoprotein-mediated cell-cell fusion, and cross-inhibited the fusion mediated by the glycoproteins from Puumala virus (PUUV). The Gc fragments interfered in ANDV cell entry by preventing membrane hemifusion and pore formation, retaining Gc in a non-resistant homotrimer stage, as described for DIII and stem peptide inhibitors of class II fusion proteins. Collectively, our results demonstrate that hantavirus Gc shares not only structural, but also mechanistic similarity with class II viral fusion proteins, and will hopefully help in developing novel therapeutic strategies against hantaviruses.CONICYT (Chile) through FONDECYT grant, Basal fundin

Localization of predicted DIII and stem fragments in ANDV Gc.

<p>(A) Molecular model for ANDV Gc in its pre-fusion conformation [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004799#pntd.0004799.ref023" target="_blank">23</a>] based on the TBEV E protein (PDB: 1SVB) [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004799#pntd.0004799.ref031" target="_blank">31</a>]. The predicted DIII is indicated in blue and the predicted domains I-II are shown in grey. (B) Scheme of the ANDV Gc primary structure indicating predicted residues for DIII (blue) and the predicted stem region (green). S indicates the stem region; TM indicates the transmembrane region; Ct indicates the cytoplasmic tail. (C) Sequence logo representation of a multiple sequence alignment including DIII and stem regions of the genus <i>Hantavirus</i> built with WebLogo [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004799#pntd.0004799.ref065" target="_blank">65</a>]. The sequence conservation at each position is represented by the overall height of the stack at that position, while the conservation of a specific residue at that position is given by the height of the symbols. Acid residues are indicated in red, basic residues in blue, apolar residues in black and polar residues in green. For the multiple sequence alignment, glycoprotein sequences were retrieved from GenBank representing the four hantavirus phylogroups [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004799#pntd.0004799.ref066" target="_blank">66</a>] from different reservoirs, including rodent-borne hantaviruses from the subfamiliies <i>Avicolinae</i> (PUUV; accession no. NP_941983.1), <i>Murinae</i> (HTNV; accession no. NP_941978.1), <i>Sigmodontinae</i> (ANDV; accession no. AAO86638.1), and also hantaviruses harbored in shrews, moles and bats from the families <i>Soricidae</i> (Thottapalayam virus; accession no. ABU82619.1), <i>Talpidae</i> (Asama virus; accession no. ACI28508.1), and <i>Rhinolophidae</i> (Longquan virus; accession no. AGI62348.1). The regions spanned by recombinant domains and peptides are indicated schematically below the logo representation by DIII, R1, R2, R2.1 and R2.2. (D) Sequence logo representation of a sequence alignment from the partial stem region of ANDV and PUUV Gc.</p