Targeting Lipid Peroxidation for Cancer Treatment

grant number RTI2018-093864-B-I00Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease.publishersversionpublishe

Introduction : geographic context, history and management for conservation

Este capítulo tiene la intención de brindar una introducción al libro. Aquí se reseñan algunas características de la reserva, como su ubicación geográfica, su historia, el proceso de adquisición por parte de la Fundación Vida Silvestre Argentina y su devenir en la actual reserva de vida silvestre que hoy es orgullo de quienes tenemos el privilegio de trabajar en ella. Se culmina con la presentación de la estructura y contenido de los diferentes capítulos que componen esta obra.This chapter is intended to provide an introduction to the book. Here we outline some features of the reserve, such as its geographical location, history, the acquisition process by the Fundación Vida Silvestre Argentina, and how it became the current wildlife reserve that makes those of us who have the privilege of working at it feel proud. It ends with the presentation of the structure and content of the different chapters that make up this book.Fil: Arias, Alejandro M.. Fundacion Vida Silvestre Argentina; ArgentinaFil: Pazos, Gustavo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Universidad Nacional de la Patagonia. Facultad de Ciencias Naturales. Sede Puerto Madryn; ArgentinaFil: Udrizar Sauthier, Daniel Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; Argentina. Universidad Nacional de la Patagonia. Facultad de Ciencias Naturales. Sede Puerto Madryn; Argentin

The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb5R

Authors would like to acknowledge the Biochemistry Department in the Faculty of Medicine at the Universidad Autónoma de Madrid for the equipment and support for some of the required reagent purchases. FCT/MCTES is also acknowledged for supporting the National Portuguese NMR Network (ROTEIRO/0031/2013-PINFRA/22161/2016, co-financed by FEDER through COMPETE 2020, POCI, PORL. We thank José Paulo da Silva for the HRMS-ESI analysis. Publisher Copyright: © 2022 by the authors.Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb5R has been observed. A search for specific inhibitors of Cb5R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb5R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb5R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb5R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future.publishersversionpublishe

Acute Effects of Work Rest Interval Duration of 3 HIIT Protocols on Cycling Power in Trained Young Adults

High-Intensity Interval Training (HIIT) is described as a succession of short duration and maximum or near-maximum intensity efforts, alternated by recovery periods during which exercise continues at a lower intensity (active recovery) or is interrupted (passive recovery). Our objective was to evaluate the acute responses of three HIIT protocols of different work/rest interval times over the total time of the session, with self-selectable load and up to exhaustion, “all out”.The sample was composed of 22 male participants (n = 22) between 19 and 24 years old. The HIIT protocol consisted of one of the three HIIT protocols, of 30, 60 and 90 s density ratio 1:1 and with passive rest, with a total exercise duration of 10 min. The test was performed in a cycloergometer set in workload mode independent of the pedaling frequency. The comparison of the three HIIT protocols shows that the duration of the work/rest intervals, starting from 30 s of work, in the cycloergometer, there are no significant differences in the levels of lactate concentration in the blood, nor in the heart rate, since a similar amount is obtained in the three protocols. The percentage of maximum power developed reached in each HIIT protocol is related to the duration of the working intervals

Diagnóstico y análisis de algunas causas que dificultan el aprendizaje del algebra lineal en estudiantes de ingeniería

En este artículo se presentan los resultados del diagnóstico y análisis de algunas causas que obstaculizan el aprendizaje del Álgebra Lineal en los estudiantes de ingeniería de la Universidad Tecnológica de Pereira. Igualmente pretende identificar la importancia que se le da a la asignatura dentro de los programas de ingeniería, mediante encuestas que se realizaron a los profesores que orientan diferentes asignaturas de matemáticas como a los directores de los diferentes programas. Además se presentan conclusiones y recomendaciones acerca del estudio

Diagnóstico y análisis de algunas causas que dificultan el aprendizaje del algebra lineal en estudiantes de ingeniería

En este artículo se presentan los resultados del diagnóstico y análisis de algunas causas que obstaculizan el aprendizaje del Álgebra Lineal en los estudiantes de ingeniería de la Universidad Tecnológica de Pereira. Igualmente pretende identificar la importancia que se le da a la asignatura dentro de los programas de ingeniería, mediante encuestas que se realizaron a los profesores que orientan diferentes asignaturas de matemáticas como a los directores de los diferentes programas. Además se presentan conclusiones y recomendaciones acerca del estudio

Algunos medios que contribuyen a mejorar el aprendizaje del álgebra lineal

Este documento contiene algunas de las estrategias metodológicas que se han venido implementando en la enseñanza de algunos cursos de álgebra lineal con los estudiantes de ingeniería de la Universidad Tecnológica de Pereira, las cuales corresponden a resultados parciales del proyecto de investigación “Estudios metodológicos para contribuir a mejorar el proceso de enseñanza_aprendizaje del Álgebra Lineal, incorporando las TIC

Ab initio and finite-temperature molecular dynamics studies of lattice resistance in tantalum

This manuscript explores the apparent discrepancy between experimental data and theoretical calculations of the lattice resistance of bcc tantalum. We present the first results for the temperature dependence of the Peierls stress in this system and the first ab initio calculation of the zero-temperature Peierls stress to employ periodic boundary conditions, which are those best suited to the study of metallic systems at the electron-structure level. Our ab initio value for the Peierls stress is over five times larger than current extrapolations of experimental lattice resistance to zero-temperature. Although we do find that the common techniques for such extrapolation indeed tend to underestimate the zero-temperature limit, the amount of the underestimation which we observe is only 10-20%, leaving open the possibility that mechanisms other than the simple Peierls stress are important in controlling the process of low temperature slip.Comment: 12 pages and 9 figure

Complexities underlying the breeding and deployment of Dutch elm disease resistant elms

Dutch elm disease (DED) is a vascular wilt disease caused by the pathogens Ophiostoma ulmi and Ophiostoma novo-ulmi with multiple ecological phases including pathogenic (xylem), saprotrophic (bark) and vector (beetle flight and beetle feeding wound) phases. Due to the two DED pandemics during the twentieth century the use of elms in landscape and forest restoration has declined significantly. However new initiatives for elm breeding and restoration are now underway in Europe and North America. Here we discuss complexities in the DED 'system' that can lead to unintended consequences during elm breeding and some of the wider options for obtaining durability or 'field resistance' in released material, including (1) the phenotypic plasticity of disease levels in resistant cultivars infected by O. novo-ulmi; (2) shortcomings in test methods when selecting for resistance; (3) the implications of rapid evolutionary changes in current O. novo-ulmi populations for the choice of pathogen inoculum when screening; (4) the possibility of using active resistance to the pathogen in the beetle feeding wound, and low attractiveness of elm cultivars to feeding beetles, in addition to resistance in the xylem; (5) the risk that genes from susceptible and exotic elms be introgressed into resistant cultivars; (6) risks posed by unintentional changes in the host microbiome; and (7) the biosecurity risks posed by resistant elm deployment. In addition, attention needs to be paid to the disease pressures within which resistant elms will be released. In the future, biotechnology may further enhance our understanding of the various resistance processes in elms and our potential to deploy trees with highly durable resistance in elm restoration. Hopefully the different elm resistance processes will prove to be largely under durable, additive, multigenic control. Elm breeding programmes cannot afford to get into the host-pathogen arms races that characterise some agricultural host-pathogen systems