NRF2, cancer and calorie restriction

16 páginas, 1 figura, 3 tablas.-- PMCID: PMC4684645The transcription factor NF-E2-related factor (NRF2) is a key regulator of several enzymatic pathways, including cytoprotective enzymes in highly metabolic organs. In this review, we summarize the ongoing research related to NRF2 activity in cancer development, focusing on in vivo studies using NRF2 knockout (KO) mice, which have helped in defining the crucial role of NRF2 in chemoprevention. The lower cancer protection observed in NRF2 KO mice under calorie restriction (CR) suggests that most of the beneficial effects of CR on the carcinogenesis process are likely mediated by NRF2. We propose that future interventions in cancer treatment would be carried out through the activation of NRF2 in somatic cells, which will lead to a delay or prevention of the onset of some forms of human cancers, and subsequently an extension of health- and lifespan.AM-M and RdC are supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. The work was partially supported by Junta de Andalucía International Projects, CVI 4887 and CVI-276, NIH Grant 1R01AG028125-01A1 and FIS Grant PI080500 of the Ministry of Health, Spain.Peer reviewe

The influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction

PMCID: PMC4138957.-- et al.Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95 % (control) or 60 % (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H2O2 production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CRinduced decreases in ROS production. © 2014 Institute of Physiology v.v.i.This work was supported by the National Institutes of Health grants R01 AG028125 and P01 AG025532.Peer Reviewe

Segmentación automática de estudios PET cardíacos con ¹³NH_3 basada en correlación iterativa

Actas de: XXVIII Congreso Anual de la Sociedad Española de Ingeniería Biomédica (CASEIB 2010). Madrid, 24-26 de noviembre de 2010.La obtención de la función de entrada en estudios dinámicos de corazón a partir de la imagen PET se realiza habitualmente mediante la selección previa de una región de interés (ROI) o utilizando procedimientos de análisis factorial para encontrar aquellas curvas actividad/tiempo que mejor se adaptan a la función de entrada. En este trabajo se presenta un método novedoso de segmentación automática y obtención de la función de entrada que utiliza mapas de correlación calculados sobre estudios dinámicos que emplean ¹³NH_3 como trazador. Partiendo de un modelo analítico inicial, se buscan las curvas temporales más parecidas en el estudio real empleando la correlación. Tomando como datos estas curvas se calculan nuevos modelos con los que realizar sucesivas iteraciones. El resultado final es tanto una segmentación automática como la curva de actividad/tiempo de cada región segmentada.Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, la RETIC-RECAVA del Ministerio de Sanidad y Consumo, y el programa ARTEMIS S2009/DPI-1802 de la Comunidad de Madrid.Publicad

El conocimiento científico producido en la UNC sobre COVID-19, recopilado en un repositorio digital de acceso abierto

Con más de 150 artículos publicados, la Colección COVID-19 del Repositorio Digital de la Universidad Nacional de Córdoba recoge los abordajes científicos y tecnológicos más recientes en torno a la crisis sanitaria provocada por el coronavirus. Este espacio reúne las producciones de grupos de investigación de distintos campos disciplinares, no solo de los relativos a la salud, y ofrece la posibilidad de consultar libre y gratuitamente información de calidad y utilidad para comprender mejor los alcances e implicancias de la pandemia. Para enviar documentos a la Oficina de Conocimiento para ser publicados en el RDU: [email protected]: Villalba, María José. Universidad Nacional de Córdoba. Prosecretaría de Comunicación Institucional. UNCiencia; Argentina.Fil: Nardi, Alejandra M. Universidad Nacional de Córdoba. Área de Gestión Institucional. Oficina de Conocimiento Abierto, Argentina

Olive Oil and the Hallmarks of Aging

Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the “hallmarks of aging”, which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all these hallmarks are targeted by dietary olive oil, particularly by virgin olive oil, since many of its beneficial effects can be accounted not only for the monounsaturated nature of its predominant fatty acid (oleic acid), but also for the bioactivity of its minor compounds, which can act on cells though both direct and indirect mechanisms due to their ability to modulate gene expression. Among the minor constituents of virgin olive oil, secoiridoids stand out for their capacity to modulate many pathways that are relevant for the aging process. Attenuation of aging-related alterations by olive oil or its minor compounds has been observed in cellular, animal and human models. How olive oil targets the hallmarks of aging could explain the improvement of health, reduced risk of aging-associated diseases, and increased longevity which have been associated with consumption of a typical Mediterranean diet containing this edible oil as the predominant fat source

jClustering, an open framework for the development of 4D clustering algorithms

We present jClustering, an open framework for the design of clustering algorithms in dynamic medical imaging. We developed this tool because of the difficulty involved in manually segmenting dynamic PET images and the lack of availability of source code for published segmentation algorithms. Providing an easily extensible open tool encourages publication of source code to facilitate the process of comparing algorithms and provide interested third parties with the opportunity to review code. The internal structure of the framework allows an external developer to implement new algorithms easily and quickly, focusing only on the particulars of the method being implemented and not on image data handling and preprocessing. This tool has been coded in Java and is presented as an ImageJ plugin in order to take advantage of all the functionalities offered by this imaging analysis platform. Both binary packages and source code have been published, the latter under a free software license (GNU General Public License) to allow modification if necessary.Funded by TEC2011-28972-C02-01, Ministerio de Ciencia e Innovación, CEN-20101014; Programa CENIT-CDTI, Ministerio de Ciencia e Innovación; S2009/DPI-1802 (ARTEMIS), Comunidad de Madrid. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Publicad

Iterative Automatic Segmentation in cardiac PET based on TAC correlation: preliminary results

Proceeding of: 2010 IEEE Nuclear Science Symposium, Medical Imaging Conference and 17th Room Temperature Semiconductor Detector Workshop (IEEE), Knoxville, Tennessee, USA, October 30 - November 6, 2010Conventional kinetic parameter estimation based on compartmental models requires an accurate estimation of arterial blood input function. To avoid invasive blood sampling, an image-derived input function can be obtained by manually defining a Region of Interest. Here we propose a new and simple, iterative method for automatic segmentation and input function calculation of PET cardiac studies using correlation as a distance metric between a priori information regarding the approximate shape of the final time-activity curve (TAC) and the actual TAC extracted from the image temporal series.This work was supported in part by the CENIT-AMIT Ingenio 2010, Ministerio de Ciencia e Innovación, TEC2007-64731, TEC 2008-06715-C02-1, RETIC-RECAVA, Ministerio de Sanidad y Consumo, and the ARTEMIS de la Comunidad de Madrid (S2009/DPI-1802) programsPublicad

Automatic TAC extraction from dynamic cardiac PET imaging using iterative correlation from a population template

This work describes a new iterative method for extracting time-activity curves (TAC) from dynamic imaging studies using a priori information from generic models obtained from TAC templates. Analytical expressions of the TAC templates were derived from TACs obtained by manual segmentation of three 13NH3 pig studies (gold standard). An iterative method for extracting both ventricular and myocardial TACs using models of the curves obtained as an initial template was then implemented and tested. These TACs were extracted from masked and unmasked images; masking was applied to remove the lungs and surrounding non-relevant structures. The resulting TACs were then compared with TACs obtained manually; the results of kinetic analysis were also compared. Extraction of TACs for each region was sensitive to the presence of other organs (e.g., lungs) in the image. Masking the volume of interest noticeably reduces error. The proposed method yields good results in terms of TAC definition and kinetic parameter estimation, even when the initial TAC templates do not accurately match specific tracer kinetics.This work is supported by the following grants: RD07/0014/2009, Subprograma RETICS, Ministerio de Ciencia e Innovación. S2009/DPI-1802 (ARTEMIS), Comunidad de Madrid. CEN-20101014, Programa CENIT, CDTI, Ministerio de Ciencia e Innovación. European Commission, EFPIA, INNOVATIVE MEDICINE INITIATIVE (PredDICT-TB project, 115337-1)Publicad

Direct PCR-free electrochemical biosensing of plant-food derived nucleic acids in genomic DNA extracts. Application to the determination of the key allergen Sola l 7 in tomato seeds

A novel and disposable electrochemical biosensor for PCR-free and selective detection of Sola l 7, a non-specific lipid transfer protein (nsLTP) found in tomato seeds associated to severe symptoms of tomato-allergic patients, is reported in this work. The methodology involves the formation of DNA/RNA heterohybrids by sandwich hybridization of a specific fragment of the Sola l 7 allergen coding sequence with appropriate RNA probes designed and described for the first time in this work. Labeling was carried out with commercial antibodies specific to the heteroduplexes and secondary antibodies conjugated with HRP onto the surface of magnetic beads. Amperometric transduction was performed upon magnetic capture of the resulting magnetic bioconjugates on screen-printed electrodes using the system H2O2/HQ. A comparison of the sandwich hybridization format with a direct approach as well as between different labeling strategies was performed. The LOD value achieved was 0.2 pM (5 amol in 25 μL). The biosensor was successfully applied to the selective analysis of the targeted Sola l 7 specific region directly in just 100 ng of non-fragmented denatured genomic DNA extracted from tomato seeds.The financial support of the Spanish Ministerio de Economía y Competitividad Research Projects, CTQ2015-64402-C2-1-R, SAF2017-86483-R and the TRANSNANOAVANSENS Program from the Comunidad de Madrid (Grant P2018/NMT-4349) are gratefully acknowledged. M.F.B. is grateful to FCT grant SFRH/BPD/78845/2011,financed by POPH–QREN–Tipologia4.1–Formação Avançada, subsidized by Fundo Social Europeu and Ministério da Ciência, Tecnologiae Ensino Superior. The author M.A.P.B. is grateful to the authors J.M.R., M.F.B., S.C., J.M.P. for the scientific assistance and suggestions shared throughout the supervision of her Master’s project and Master’s thesis at University of Minho. The author M.A.P.B. also acknowledges the Department of Biology (DB) and the Centre of Molecular and Environmental Biology (CBMA) from University of Minho (UM), Braga,Portugal, by providing all the conditions leading to the Master's thesis in“Biophysics and Bionanosystems”. Financial support of M.A.P.B. forthis work was provided by a fellowship within the programme Erasmus+ scholarship/Portugal, which allowed performing the laboratorial work at the University Complutense of Madrid, Madrid, Spain. The author J.M.R. acknowledges CBMA-UM and DB-UM, Portugal, by the conditions provided. J.M.R. is also grateful to the Green Chemistry Laboratory (LAQV)–Research center Chemistry and Technology Network (REQUIMTE), and the Department of Chemistry and Biochemistry (DCB) from Faculty of Sciences, University of Porto(FCUP), Porto, Portugal, where currently he is researcher. J.M.R. acknowledges the financial support of the strategic programmes UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569) and PTDC/SAUNUT/30448/2017 (POCI-01-0145-FEDER-030448) and M.F.B. the financial support of the projects PTDC/QUI-QAN/30735/2017 and UID/QUI/50006/2019, funded by national funds through Fundação para a Ciência e Tecnologia [Foundation for Science and Technology](FCT-I.P.)/Ministério da Ciência, Tecnologia e Ensino Superior [Ministry of Science, Technology and Higher Education] (MCTES), and Fundo Europeu de Desenvolvimento Regional [European RegionalDevelopment Fund] (FEDER), under the scope of the COMPETE2020–Programa Operacional Competitividade e Internacionalização[COMPETE2020–Competitiveness and InternationalizationOperational Program, POCI]. S.B. acknowledges the financial support from MINECO through the“Juan de la Cierva” program.info:eu-repo/semantics/publishedVersio

Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats

PMCID: PMC4104696In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18. months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.Supported by NIH grant 1R01AG028125-01A1 (to JJR, PN and JMV), Ministerio de Economía y Competitividad and European FEDERBFU2011-23578 (to JMV), Junta de Andalucía Proyectos de Excelencia grant P09-CVI-4887 (to JMV), Junta de Andalucía Proyectos Internacionales (to JMV), and BIO-276 (Junta de Andalucía and the University of Córdoba, to JMV and EGC). JALD and LFdR were funded by predoctoral fellowships of the Spanish Ministerio de Educación and by BIO-276. HK was funded by a predoctoral fellowship of the Agencia Española de Cooperación Internacional al Desarrollo and by BIO-276.Peer Reviewe