REPISALUD (Instituto de Salud Carlos III)
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A Survey for Human Tissue-Level Determinants of CAV1 Regulation and Function.
No full textM.Á.d.P. is a recipient of grants from the Spanish Ministry of Science and Innovation (MCIN) (refs. SAF2017–83130-R cofunded by “ERDF A way of making Europe”, PID2020-118658RB-I00, PDC2021–121572-100 cofunded by “European Union NextGeneration EU/PRTR”), Asociación Española Contra el Cáncer foundation (AECC; PROYE20089DELP); La Marató TV3 foundation (201936–30-31), Fundación Obra social La Caixa (AtheroConvergence, HR20–00075; of which he is the coordinator) and Comunidad Autónoma de Madrid/FEDER (Tec4Bio consortium, ref. S2018/NMT¬4443). M.S.-Á. is a recipient of a Ramón y Cajal research contract from MCIN (RYC2020–029690-I) and research grants PID2021-128106NA-I00 and CNS2023-144831, all from Spanish MCIN. M.Á.d.P. received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement 641639 in the context of the BIOPOL ITN consortia, of which V.J.-J. was an ESR. V.J.-J. was also supported by the La Caixa and Deutscher Akademischer Austauschdienst scholarship. M.A.S. is Robert W. Berliner Professor of Medicine and co-recipient of the AtheroConvergence grant from Fundación Obra social La Caixa (HR20–00075). The CNIC is
supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS.CAV1 is a protein-coding gene linked to several disorders, including cancer, lipodystrophy, and cardiovascular diseases. While its ability to respond to various mechanical and metabolic stimuli has been documented, a comprehensive understanding of its physiological regulation in humans is lacking. We leveraged the comprehensiveness of human post-mortem tissue data from the Genotype-Tissue Expression (GTEx) consortium, systematically exploring the sources of variability in CAV1 transcriptional levels using extensive bulk and single-nuclei RNA-seq datasets. This human-centric approach, avoiding inter-species comparisons, constitutes a unique resource to explore CAV1 regulation within the complexity of human tissues. Notably, cell type proportion was identified as a major determinant of CAV1 transcription levels across tissues. Donor physiological conditions, including disease states and end-of-life circumstances, also exhibited a tissue-specific influence. Among primary upstream regulators associated with CAV1, chromatin modifiers stood out, especially SMARCA2, which showed a positive correlation across tissues, and PRC2 complexes, which exhibited tissue-specific correlation. Upstream regulatory networks determining CAV1 levels are also enriched for annotations such as mechanobiology (e.g., TEAD4), immunity (e.g., RELA and STAT3), and metabolism (e.g., MYC and NRF1). A remarkable observation was a strong correlation between CAV1 and the relative infiltration of immune cells across tissues, supporting a potential role for CAV1 as a marker and driver of tissue immune infiltration.S
MoMo. Monitorización de la mortalidad diaria por todas las causas y atribuible a temperaturas. Situación a 10 de septiembre de 2025.
No full textDesde el 01 de enero de 2023 MoMo ha identificado a nivel nacional -8.961 exceso de defunciones por todas las causas y 16.783 defunciones atribuibles a temperatura.N
Elucidating the functional role of the novel BdP50 protein and extracellular vesicles in the human erythrocyte infection by Babesia divergens
No full textBabesia divergens is a blood-borne parasite that invades, replicates within and destroys red blood cells (RBCs) during its asexual life cycle, causing babesiosis in humans and cattle. This study focuses on BdP50, a putative B. divergens glycosylphosphatidylinositol-anchored protein involved in the parasite life cycle. BdP50 is found on the surface of B. divergens invasive parasites (merozoites) as well as on extracellular vesicles (Bd-derived EVs). These EVs are secreted by parasites cultured in fresh human RBCs and, in addition to BdP50, are enriched in human and parasite proteins, including proteins related to the parasite invasion process. BdP50 binds to RBCs and could mediate interactions of free merozoites and Bd-derived EVs with the host cell. Anti-BdP50 antibodies support this by blocking the BdP50 protein and inhibiting up to 88% of merozoite entry into naïve RBCs. This reinforces the role of BdP50 in parasite-host cell interactions and invasion. However, the inhibitory effect of BdP50 antibodies begins to gradually decrease slightly several hours after invasion, leading to a progressive increase in B. divergens infected RBCs over time. Consistent with these findings, our in vitro de novo infection assays showed that Bd-derived EVs, in addition to promoting parasite propagation, display proteins such as BdP50 that mimic the merozoite surface to likely attenuate the blocking effect of antibodies, thereby ensuring the parasite survival during subsequent rounds of invasion and growth. Given the role of BdP50 and Bd-derived EVs in the B. divergens life cycle, this study could have future implications for developing new approaches to interfere with parasite invasion proteins and Bd-derived EVs functions.This work was supported by the Instituto de Salud Carlos III, Madrid, Spain (PI20CIII-00037 to EM and LMG) and the Consejería de Educación, Ciencia y Universidades, Comunidad de Madrid, Madrid, Spain; (TEC-2024/BIO-66 to EM and LMG). The funders had no role in study desgin, data collection and analysis, deccision to publish, or preparation manuscript.S
Shaping current European mitochondrial haplogroup frequency in response to infection: the case of SARS-CoV-2 severity.
No full textThe frequency of mitochondrial DNA haplogroups (mtDNA-HG) in humans is known to be shaped by migration and repopulation. Mounting evidence indicates that mtDNA-HG are not phenotypically neutral, and selection may contribute to its distribution. Haplogroup H, the most abundant in Europe, improved survival in sepsis. Here we developed a random forest trained model for mitochondrial haplogroup calling using data procured from GWAS arrays. Our results reveal that in the context of the SARS-CoV-2 pandemic, HV branch were found to represent protective factors against the development of critical SARS-CoV-2 in an analysis of 14,349 patients. These results highlight the role of mtDNA in the response to infectious diseases and support the proposal that its expansion and population proportion has been influenced by selection through successive pandemics.The authors thank M. M. Muñoz-Hernandez, R. Martínez de Mena and E.R. Martínez Jiménez, for technical assistance. Scheme figures were made with BioRender. We particularly acknowledge all the patients, Banco Nacional de ADN, Biobanco del Sistema de Salud de Aragón, Biobanc Fundació Institut d'Investigació Sanitària Illes Balears, Biobanco del Complexo Hospitalario Universitario de Santiago, Biobanco Vasco, for their collaboration and providing materials. JAE laboratory is supported by: RTI2018-099357-B-I00 and PID2021-1279880B-and TED2021-131611B-I00 funded by MCIN/AEI/10.13039/501100011033 and the, and CIBERFES (CB16/10/00282), Human Frontier Science Program (grant RGP0016/2018), and Leducq Transatlantic Networks (17CVD04). MR-M is supported by a FPI/PRE2021-097721 fellowship. JAE and FSC are supported by TED2021-131611B-I00 funded by MCIN/AEI/10.13039/501100011033 and the European Union “NextGenerationEU”/Plan de Recuperación Transformación y Resiliencia -PRTR. FSC received funding [grant no. PID2022-141527OB-I00] by the MCIN/AEI/10.13039/501100011033/ and by FEDER Una manera de hacer Europa. This work was supported by Fundación Amancio Ortega Gaona, Banco de Santander S.A. and Instituto de Salud Carlos III (COV20/00622) and the European Regional Development Fund. Genotyping service was carried out at CEGEN-PRB3-ISCIII, supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDF. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation) and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033).S
Proteome evaluation of the biological activity of grape seed extract (GSE) on the intestine of rats.
No full textGrape seed extract (GSE) is rich in polyphenols and has garnered attention for its potential health benefits, particularly in the gastrointestinal system. This study explores the principal effects of consuming a low dose of GSE on the intestinal proteome. Using a rat model, we examined the ileum proteomes of rats supplemented with GSE compared with a control group without supplementation. Particularly, this study was conducted using the label-free sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) quantitative proteomics to describe ileum proteome changes derived from GSE flavanols consumption, characterizing its possible mechanisms of action. Our results highlight the substantial impact of GSE on the ileum proteome, suggesting potential mechanisms through which GSE exerts its effects. The observed protein regulation patterns indicate significant alterations in metabolic and immune regulatory pathways, highlighting the importance of considering individual variability and physiological context when evaluating the potential effects of GSE on gastrointestinal function.This research project was supported by the University of Castilla-La Mancha and the European Regional Development Fund (FEDER) under regional project grants: 2019-GRIN-26992, 2019-GRIN-27164, 2020-GRIN-28803, 2020-GRIN-28744, 2021-GRIN-31106 and 2021-GRIN-30987; and national project grant RTI2018-098643-B-I00 funded by Ministerio de Ciencia, Innovación y Universidades. Eduardo Guisantes-Batan is grateful to the European Social Fund and the University of Castilla-La Mancha for co-funding his predoctoral contract 2018/12504]. Sara Artigas-Jerónimo is supported under the FJC2021-047764-I grant, funded by MCIN/AEI/10.13039/501100011033 and the Europe Union “NextGenerationEU”/PRTR. The authors acknowledge their gratitude to “Les Dérives Résiniques et Terpéniques” for providing the grape seed extract using in this research work and Sergio Moreno for the excellent technical assistance.S
Low-intensity focused ultrasound for essential tremor and psychiatric pathology
No full textEl Ultrasonido focalizado de baja intensidad (LIFU, del inglés low-intensity focused ultrasound) es uno de los desarrollos técnicos recientes más prometedores en medicina, y aparece como una tecnología no invasiva con potencial para el tratamiento de distintas patologías. Consiste en aplicar ondas de sonido originadas a partir de vibraciones generadas en un transductor. Esta energía es focalizada en un punto fijo y se va depositando por los tejidos que atraviesa. El uso de ultrasonidos focalizados para tratamiento puede dividirse en dos categorías de acuerdo a la intensidad aplicada: LIFU (baja intensidad) e HIFU (alta intensidad). En general, la técnica del ultrasonido focalizado varía según la aplicación clínica. No obstante, para evitar efectos secundarios indeseados, es importante la retroalimentación de imágenes en tiempo real para monitorizar variables relevantes. Por ello, se utiliza la resonancia magnética (RM) junto con el ultrasonido focalizado, especialmente cuando la patología es neurológica. El LIFU está dirigido a pacientes con diversas patologías. En esta Ficha de Evaluación se recoge la evidencia científica de la utilización de LIFU para el tratamiento de temblor esencial y patología neuropsiquiátrica
Mitochondrial response to fever boosts T1-driven inflammatory responses.
No full textIncreased body temperature, both locally and systemically, is a key feature of the inflammatory response. Heat is associated with increased blood flow to affected areas and increased immune infiltrate, yet increased temperature has also been described to have direct effects on immune cell function. In a recent study, Heintzman, et al investigated the effect of febrile temperature (39 °C) on T cell function. They describe increased T1 function and fitness accompanied by a decrease in regulatory T cell suppressive function. These findings add another important consequence to our understanding of fever responses.Work in the DS laboratory is funded by the CNIC; by the European Union’s Horizon 2020 research and innovation program under grant agreement ERC-2016-Consolidator Grant 725091; by Ministerio de Ciencia, Innovación y Universidades (MICIU) PID2022-137712OB-I00, CPP2021-008310, and CPP2022-009762 MCIN/AEI/10.13039/501100011033 Agencia Estatal de Investigación, Unión Europea NextGenerationEU/ PRTR; by Comunidad de Madrid (P2022/BMD-7333 INMUNOVAR-CM); by Scientific Foundation of the Spanish Association Against Cancer (AECC- PRYGN246642SANC); by Worldwide Cancer Research WWCR-25-0080; by European Union ERC-2023-PoC; by a research agreement with Inmunotek S.L.; and by “la Caixa” Foundation (LCF/PR/HR23/52430012 and LCF/PR/HR22/52420019).S
Trajectories of adherence to an obesogenic dietary pattern and changes in diet quality, food intake, and adiposity during adolescence.
No full textContemporary longitudinal data on dietary patterns (DP) during adolescence are scarce. This study aimed to identify trajectories of adherence to an obesogenic DP and changes in diet quality (DQ), related food consumption, and adiposity markers during adolescence. A cohort of 600 adolescents (293 girls, 48.8%) attending 24 secondary schools enrolled on the SI! Program for Secondary Schools trial in Spain was assessed when participants were approximately 12, 14, and 16 years old. An energy-dense, high-fat, and low-fiber (obesogenic) DP was derived at each time point by reduced rank regression (RRR) using the percentage energy intake from fat, fiber density, and dietary energy density as intermediate variables. Based on each participant's resulting scores, trajectories of adherence to the obesogenic DP were identified by latent class trajectory modeling. Adjusted associations between trajectories, DQ and food consumption changes, and adiposity markers during adolescence were analyzed with generalized linear models. Based on adherence to the obesogenic DP during adolescence, four stable trajectory groups (from lowest to highest adherence) were identified: trajectory 1 (44 participants [7.3%]), trajectory 2 (180 participants [30.0%]), trajectory 3 (292 participants [48.7%]), and trajectory 4 (84 participants [14.0%]). Overall DQ was moderate, but showed a gradient across trajectories, with trajectory 1 having the best quality. Although the identified trajectories were stable, individuals in the group with the lowest adherence to the obesogenic DP (trajectory 1) significantly improved their overall DQ over time, whereas those with the highest adherence (trajectory 4) showed the opposite trend. The group of adolescents in trajectory 4 had the least healthy central adiposity profile when ∼16 years old. Four stable trajectories of adherence to an obesogenic DP were identified in a large cohort of adolescents, with DQ decreasing as adherence to the DP increased. Although adherence to the DP was stable, differences in food intake between trajectories widened over time, resulting in increased central adiposity in participants with the highest adherence to the pattern at the end of the study. Further research is needed to explore the determinants of adherence to obesogenic DPs in adolescence and to evaluate their effects on adiposity and overall health later in life.The SI! Program for Secondary School trial was funded by the Fundació la Marató de TV3 (grant number 369/C/2016); ‘la Caixa’ Foundation (grant number LCF/PR/CE16/10700001); the Ministerio de Ciencia e Innovación (grant number AGL2016–75329-R); the Generalitat de Catalunya (2021-SGR-00334); and the SHE Foundation. J.M-G is a recipient of grant FPU21/04891 ( Ayudas para la formación de profesorado universitario, FPU-2021) from the Ministerio de Educación, Cultura y Deporte. AT-R is a Serra Húnter fellow. RF-J is recipient
of grant PI22/01560 funded by the Instituto de Salud Carlos III (ISCIII)-Fondo de Investigación Sanitaria and co-funded by the European Union. The CNIC is supported by the ISCIII, the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). INSA-UB is a María de Maeztu Center of Excellence (grant CEX2021-001234-M funded by MICIN/AEI/FEDER, UE).S
El ISCIII publica una monografía sobre contaminación atmosférica y salud
No full textMonografía disponible en: https://hdl.handle.net/20.500.12105/26722El Instituto de Salud Carlos III (ISCIII) ha publicado una monografía sobre el ‘Impacto a corto plazo en España de la contaminación atmosférica sobre los ingresos hospitalarios urgentes por diferentes causas específicas y su estimación económica’, que incluye información general sobre cómo la contaminación atmosférica afecta a la salud, junto con los resultados de 11 investigaciones publicadas y lideradas en los dos últimos años por la Unidad de Referencia en Cambio Climático, Salud y Medio Ambiente Urbano de la Escuela Nacional de Sanidad (ENS-ISCIII)
MoMo. Monitorización de la mortalidad diaria por todas las causas y atribuible a temperaturas. Situación a 23 de julio de 2025.
No full textDesde el 01 de enero de 2023 MoMo ha identificado a nivel nacional -11.184 exceso de defunciones por todas las causas y 14.494 defunciones atribuibles a temperatura.N