Genetically modified ZIKA virus as a microRNA-sensitive oncolytic virus against central nervous system tumors.

Here we introduce a first-in-class microRNA-sensitive oncolytic Zika virus (ZIKV) for virotherapy application against central nervous system (CNS) tumors. The described methodology produced two synthetic modified ZIKV strains that are safe in normal cells, including neural stem cells, while preserving brain tropism and oncolytic effects in tumor cells. The microRNA-sensitive ZIKV introduces genetic modifications in two different virus sites: first, in the established 3'UTR region, and secondly, in the ZIKV protein coding sequence, demonstrating for the first time that the miRNA inhibition systems can be functional outside the UTR RNA sites. The total tumor remission in mice bearing human CNS tumors, including metastatic tumor growth, after intraventricular and systemic modified ZIKV administration, confirms the promise of this virotherapy as a novel agent against brain tumors-highly deadly diseases in urgent need of effective advanced therapies.

Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology.

Selenium (Se) role in obesity is not clear. In addition, information on Se's role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.

The Human Pathogen Paracoccidioides brasiliensis Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface.

Paracoccidioides brasiliensis is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense. Among them, the peroxiredoxins are highlighted, since some estimates suggest that they are capable of decomposing most of the hydroperoxides generated in the host's mitochondria and cytosol. We presently characterized a unique P. brasiliensis 1-Cys peroxiredoxin (PbPrx1). Our results reveal that it can decompose hydrogen peroxide and organic hydroperoxides very efficiently. We showed that dithiolic, but not monothiolic compounds or heterologous thioredoxin reductant systems, were able to retain the enzyme activity. Structural analysis revealed that PbPrx1 has an α/ß structure that is similar to the 1-Cys secondary structures described to date and that the quaternary conformation is represented by a dimer, independently of the redox state. We investigated the PbPrx1 localization using confocal microscopy, fluorescence-activated cell sorter, and immunoblot, and the results suggested that it localizes both in the cytoplasm and at the cell wall of the yeast and mycelial forms of P. brasiliensis, as well as in the yeast mitochondria. Our present results point to a possible role of this unique P. brasiliensis 1-Cys Prx1 in the fungal antioxidant defense mechanisms.

Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.

Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.

Hypercaloric Diet-Induced Obesity and Obesity-Related Metabolic Disorders in Experimental Models.

Overnutrition and obesity have developed into a major public health problem across different parts of the world. Epidemiological studies have shown that excessive intake of dietary components, such as fatty acids and/or sugars, can promote obesity. In this context, the use of dietary intervention in animal models that respond to a diet similar to humans is useful to understand this preventable, multifactorial disease. The aim of this chapter is to aid researchers in choosing specific nutritional interventions and animal strains to induce obesity and obesity-related morbidities in experimental models.