Dr. Villagrán-Orellana, Marcelo

Background: little information is availaible on the effect of fructose on bile lipids. The first stage in the formation of gallstones corresponds to biliary cholesterol crystallization, derived from the vesicular transporters. The aim of this study was to investigate the influence of consuming diets with different fructose concentrations on serum lipids and their implications on gallstones formation. Methods: BALB/c mice divided into a control group as well as groups were treated with different fructose concentrations (10 %, 30 %, 50 % or 70 %) for different periods (1, 2 or 5 months). Blood, liver and bile samples were obtained. In bile samples, cholesterol and phospholipids levels were analyzed, and cholesterol transporters (vesicles and micelles) were separated by gel filtration chromatography. Results: treated animals showed: 1) increases in body weight similar to the control group; 2) a significant increase in plasma triglycerides only at very high fructose concentrations; 3) a significant increase in total serum cholesterol in the treatment for 1 month; 4) no variations in HDL-cholesterol; 5) a significant increase in serum glucose only at very high fructose concentrations in the second month of treatment; 6) no differences in the plasma alanine-aminotransferase activity; 7) a significant increase in liver triglyceride levels only at very high fructose concentrations; 8) no change in biliary lipid concentrations or in micellar and vesicular phospholipids. Conclusion: changes in plasma, liver and bile lipids were only observed at very high fructose concentrations diets. We conclude that fructose apparently does not alter the gallstone formation process in our experimental model.

Introducción: La diabesidad se define como la coexistencia de obesidad y diabetes mellitus tipo 2 (DMT2). En Chile su prevalencia aún no ha sido definida. El objetivo de este estudio fue determinar la prevalencia de prediabesidad y diabesidad en adultos chilenos. Material y Método: Estudio transversal que incluyó 4.985 adultos mayores de 18 años de la Encuesta Nacional de Salud 2016-2017. El estado nutricional fue determinado por índice de masa corporal y DMT2 por una glicemia en ayuno ≥126 mg/dL o auto-reporte médico. Utilizando la combinación de estas dos variables, se definieron 6 fenotipos: normal sin diabetes, normo-diabetes, sobrepeso sin diabetes, prediabesidad, obesidad sin diabetes y diabesidad. La prevalencia de estos fenotipos se estudió según características sociodemográficas y estilos de vida. Resultados: La prevalencia de diabesidad, prediabesidad y normo-diabetes fue de 5,7%, 3,6% y 2,5%, respectivamente. Adicionalmente, la prevalencia de diabesidad fue mayor en mujeres, en personas con menos de 8 años de escolaridad y en aquellos con una edad de diagnóstico entre 45 y 46 años. Conclusión: El 9,3% de la población presentó prediabesidad o diabesidad, con una mayor proporción de los casos de diabesidad en mujeres y personas con bajo nivel de escolaridad. Considerando las proyecciones de aumento de obesidad y DMT2 en Chile, resulta urgente generar acciones y estrategias en esta materia, ya que una gran proporción de los casos de estas patologías pueden ser prevenibles.

Alternariol is a toxic metabolite of Alternaria fungi and studies have shown multiple potential pharmacological effects. To outline the anticancer effects and mechanisms of alternariol and its derivatives based on database reports, an updated search of PubMed/MedLine, ScienceDirect, Web of Science, and Scopus databases was performed with relevant keywords for published articles. The studies found to suggest that this mycotoxin and/or its derivatives have potential anticancer effects in many pharmacological preclinical test systems. Scientific reports indicate that alternariol and/or its derivatives exhibit anticancer through several pathways, including cytotoxic, reactive oxygen species leading to oxidative stress and mitochondrial dysfunction-linked cytotoxic effect, anti- inflammatory, cell cycle arrest, apoptotic cell death, genotoxic and mutagenic, anti-proliferative, autophagy, and estrogenic and clastogenic mechanisms. In light of these results, alternariol may be one of the hopeful chemotherapeutic agents.

GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1’s transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in Xenopus laevis oocytes. All the mutants decreased the uptake of both substrates to less than 50%. The partial effect of the N317A mutant in transporting dehydroascorbic acid was associated with a 30% decrease in the Vmax compared to the wildtype GLUT1. The results show that both substrates share the eight residues studied in GLUT1, albeit with a differential contribution of N317. Our work, combining docking with functional studies, marks the first to identify structural determinants of oxidized vitamin C’s transport via GLUT1.

Objective: To investigate the association between a lifestyle score and all-cause mortality in the Chilean population. Design: Prospective study. Settings: The score was based on seven modifiable behaviours: salt intake, fruit and vegetable intake, alcohol consumption, sleep duration, smoking, physical activity and sedentary behaviours. 1-point was assigned for each healthy recommendation. Points were summed to create an unweighted score from 0 (less healthy) to 7 (healthiest). According to their score, participants were then classified into: less healthy (0–2 points), moderately healthy (3–4 points) and the healthiest (5–7 points). Associations between the categories of lifestyle score and all-cause mortality were investigated using Cox proportional hazard models adjusted for confounders. Nonlinear associations were also investigated. Participants: 2706 participants from the Chilean National Health Survey 2009–2010. Results: After a median follow-up of 10·9 years, 286 (10·6 %) participants died. In the maximally adjusted model, and compared with the healthiest participants, those less healthy had 2·55 (95 % CI 1·75, 3·71) times higher mortality risk due to any cause. Similar trends were identified for the moderately healthy group. Moreover, there was a significant trend towards increasing the mortality risk when increasing unhealthy behaviours (hazard ratio model 3: 1·61 (95 % CI 1·34, 1·94)). There was no evidence of nonlinearity between the lifestyle score and all-cause mortality. Conclusion: Individuals in the less healthy lifestyle category had higher mortality risk than the healthiest group. Therefore, public health strategies should be implemented to promote adherence to a healthy lifestyle across the Chilean population.

Introducción: La lactancia materna (LM) es un factor protector contra la obesidad infantil; sin embargo, los mecanismos a través de los cuales ejerce este efecto aún no están claros. El objetivo fue describir los mecanismos asociados al efecto protector que ejerce la lactancia materna contra la obesidad infantil. Métodos: Se utilizaron los buscadores PUBMED, SCOPUS, Cochrane Library y Scielo para desarrollar una revisión descriptiva de la evidencia científica. Las palabras clave fueron: lactancia materna, obesidad, mecanismo y dieta. Se revisaron artículos en español e inglés, desde 1977 hasta el 2020. Resultados: El efecto protector de la LM contra la obesidad infantil está dado por una combinación de varios mecanismos, se destaca su composición nutricional y el aporte de sustancias bioactivas, algunas de ellas reguladoras de la ingesta energética. Los lactantes que reciben LM por más tiempo seleccionan alimentos más saludables en etapa preescolar, independiente de factores sociodemográficos. También han sido descritos efectos en la adiposidad, el control del peso corporal y la ingesta energética mediante regulación de la programación epigenética y de la microbiota intestinal. Conclusión: La LM es un proceso único, que interacciona de forma compleja con factores del crecimiento y desarrollo de los lactantes y preescolares. Su rol protector contra la obesidad ha sido asociado a diversos mecanismos. Sin embargo, se requiere de nuevas investigaciones para comprender los alcances que puede presentar la LM en la etapa pediátrica y su rol en la prevención de la obesidad.

The study describes the current state of knowledge on nanotechnology and its utilization in medicine. The focus in this manuscript was on the properties, usage safety, and potentially valuable applications of chitosan-based nanomaterials. Chitosan nanoparticles have high importance in nanomedicine, biomedical engineering, discovery and development of new drugs. The manuscript reviewed the new studies regarding the use of chitosan-based nanoparticles for creating new release systems with improved bioavailability, increased specificity and sensitivity, and reduced pharmacological toxicity of drugs. Nowadays, effective cancer treatment is a global problem, and recent advances in nanomedicine are of great importance. Special attention was put on the application of chitosan nanoparticles in developing new system for anticancer drug delivery. Pre-clinical and clinical studies support the use of chitosan-based nanoparticles in nanomedicine. This manuscript overviews the last progresses regarding the utilization, stability, and bioavailability of drug nanoencapsulation with chitosan and their safety.

Type 2 diabetes Mellitus (T2DM) prevalence has significantly increased worldwide in recent years due to population age, obesity, and modern sedentary lifestyles. The projections estimate that 439 million people will be diabetic in 2030. T2DM is characterized by an impaired β-pancreatic cell function and insulin secretion, hyperglycemia and insulin resistance, and recently the epigenetic regulation of β-pancreatic cells differentiation has been underlined as being involved. It is currently known that several bioactive molecules, widely abundant in plants used as food or infusions, have a key role in histone modification and DNA methylation, and constituted potential epidrugs candidates against T2DM. In this sense, in this review the epigenetic mechanisms involved in T2DM and protein targets are reviewed, with special focus in studies addressing the potential use of phytochemicals as epidrugs that prevent and/or control T2DM in vivo and in vitro. As main findings, and although some controversial results have been found, bioactive molecules with epigenetic regulatory function, appear to be a potential replacement/complementary therapy of pharmacological hypoglycemic drugs, with minimal side effects. Indeed, natural epidrugs have shown to prevent or delay the T2DM development and the morbidity associated to dysfunction of blood vessels, eyes and kidneys due to sustained hyperglycemia in T2DM patients.