33 research outputs found

    The transcriptional and mutational landscapes of lipid metabolism-related genes in colon cancer

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    Metabolic alterations encountered in tumors are well recognized and considered as a hallmark of cancer. In addition to Warburg Effect, epidemiological and experimental studies support the crucial role of lipid metabolism in colorectal cancer (CRC). The overexpression of four lipid metabolism-related genes (ABCA1, ACSL1, AGPAT1 and SCD genes) has been proposed as prognostic marker of stage II CRC (ColoLipidGene signature). In order to explore in depth the transcriptomic and genomic scenarios of ABCA1, ACSL1, AGPAT1 and SCD genes, we performed a transcriptomic meta-analysis in more than one thousand CRC individuals. Additionally we analyzed their genomic coding sequence in 95 patients, to find variants that could orchestrate CRC prognosis. We found that genetic variant rs3071, located on SCD gene, defines a 9.77% of stage II CRC patients with high risk of death. Moreover, individuals with upregulation of ABCA1 and AGPAT1 expression have an increased risk of CRC recurrence, independently of tumor stage. ABCA1 emerges as one of the main contributors to signature's prognostic effect. Indeed, both high ABCA1 expression and presence of tumoral genetic variants located in ABCA1 coding region, seem to be associated with CRC risk of death. In addition the non-synonymous polymorphism rs2230808, located on ABCA1, is associated with gene expression. Patients carrying at least one copy of minor allele showed higher levels of ABCA1 expression than patients carrying homozygous major allele. This study broaden the prognostic value of ABCA1, ACSL1, AGPAT1 and SCD genes, independently of CRC tumor stage, leading to future precision medicine approaches and "omics"-guided therapiesMinisterio de Economía y Competitividad del Gobierno de España (MINECO, Plan Nacional I+D+i AGL2016-76736-C3), Gobierno regional de la Comunidad de Madrid (P2013/ABI-2728, ALIBIRD-CM) and EU Structural Fund

    ColoLipidGene: Signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

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    Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolismrelated genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk groupThis work was supported by Ministerio de Ciencia e Innovación del Gobierno de España (Plan Nacional I + D + i AGL2013–48943-C2–2-R and IPT-2011–1248-060000), Comunidad de Madrid (P2013/ABI-2728. ALIBIRDCM) and European Union Structural Funds. CIBEREHD is funded by the Instituto de Salud Carlos III. This is a collaborative study between the Molecular Oncology Unit of The Institute of Advanced Studies of Madrid IMDEA Food and the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD

    A Novel Circulating MicroRNA for the Detection of Acute Myocarditis.

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    The diagnosis of acute myocarditis typically requires either endomyocardial biopsy (which is invasive) or cardiovascular magnetic resonance imaging (which is not universally available). Additional approaches to diagnosis are desirable. We sought to identify a novel microRNA for the diagnosis of acute myocarditis. To identify a microRNA specific for myocarditis, we performed microRNA microarray analyses and quantitative polymerase-chain-reaction (qPCR) assays in sorted CD4+ T cells and type 17 helper T (Th17) cells after inducing experimental autoimmune myocarditis or myocardial infarction in mice. We also performed qPCR in samples from coxsackievirus-induced myocarditis in mice. We then identified the human homologue for this microRNA and compared its expression in plasma obtained from patients with acute myocarditis with the expression in various controls. We confirmed that Th17 cells, which are characterized by the production of interleukin-17, are a characteristic feature of myocardial injury in the acute phase of myocarditis. The microRNA mmu-miR-721 was synthesized by Th17 cells and was present in the plasma of mice with acute autoimmune or viral myocarditis but not in those with acute myocardial infarction. The human homologue, designated hsa-miR-Chr8:96, was identified in four independent cohorts of patients with myocarditis. The area under the receiver-operating-characteristic curve for this novel microRNA for distinguishing patients with acute myocarditis from those with myocardial infarction was 0.927 (95% confidence interval, 0.879 to 0.975). The microRNA retained its diagnostic value in models after adjustment for age, sex, ejection fraction, and serum troponin level. After identifying a novel microRNA in mice and humans with myocarditis, we found that the human homologue (hsa-miR-Chr8:96) could be used to distinguish patients with myocarditis from those with myocardial infarction. (Funded by the Spanish Ministry of Science and Innovation and others.).Supported by a grant (PI19/00545, to Dr. Martín) from the Ministry of Science and Innovation through the Carlos III Institute of Health–Fondo de Investigación Sanitaria; by a grant from the Biomedical Research Networking Center on Cardiovascular Diseases (to Drs. Martín, Sánchez-Madrid, and Ibáñez); by grants (S2017/BMD-3671-INFLAMUNE-CM, to Drs. Martín and Sánchez-Madrid; and S2017/BMD-3867-RENIM-CM, to Dr. Ibáñez) from Comunidad de Madrid; by a grant (20152330 31, to Drs. Martín, Sánchez-Madrid, and Alfonso) from Fundació La Marató de TV3; by grants (ERC-2011-AdG 294340-GENTRIS, to Dr. Sánchez-Madrid; and ERC-2018-CoG 819775-MATRIX, to Dr. Ibáñez) from the European Research Council; by grants (SAF2017-82886R, to Dr. Sánchez-Madrid; RETOS2019-107332RB-I00, to Dr. Ibáñez; and SAF2017-90604-REDT-NurCaMeIn and RTI2018-095928-BI00, to Dr. Ricote) from the Ministry of Science and Innovation; by Fondo Europeo de Desarrollo Regional (FEDER); and by a 2016 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation to Dr. Martín. The National Center for Cardiovascular Research (CNIC) is supported by the Carlos III Institute of Health, the Ministry of Science and Innovation, the Pro CNIC Foundation, and by a Severo Ochoa Center of Excellence grant (SEV-2015-0505). Mr. Blanco-Domínguez is supported by a grant (FPU16/02780) from the Formación de Profesorado Universitario program of the Spanish Ministry of Education, Culture, and Sports. Ms. Linillos-Pradillo is supported by a fellowship (PEJD-2016/BMD-2789) from Fondo de Garantía de Empleo Juvenil de Comunidad de Madrid. Dr. Relaño is supported by a grant (BES-2015-072625) from Contratos Predoctorales Severo Ochoa para la Formación de Doctores of the Ministry of Economy and Competitiveness. Dr. Alonso-Herranz is supported by a fellowship from La Caixa–CNIC. Dr. Caforio is supported by Budget Integrato per la Ricerca dei Dipartimenti BIRD-2019 from Università di Padova. Dr. Das is supported by grants (UG3 TR002878 and R35 HL150807) from the National Institutes of Health and the American Heart Association through its Strategically Focused Research Networks.S

    European journalism observatory: An international consolidated platform for training and professional networks in the Faculty of Information Sciences

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    El objetivo principal de este proyecto Innova-Docenia era ampliar y consolidar una plataforma de formación internacional y consolidada, para alumnos y alumnas de la Facultad de Ciencias de la Información, como parte del European Journalism Observatory (EJO), fundado por el Instituto Reuters de la Universidad de Oxford. Se trataba de afianzar EJO Spain como plataforma de formación y escaparate de las acciones implementadas en España, donde la Universidad Complutense de Madrid se convertía en el socio español principal. El Observatorio Europeo de Periodismo (EJO), una red de instituciones independientes y sin ánimo de lucro del campo de la comunicación de 14 países, tiene como objetivo tender puentes entre la investigación y la práctica del periodismo en Europa y fomentar el profesionalismo y la libertad de prensa. Promueve el diálogo entre investigadores y profesionales de los medios. Acerca los resultados de la investigación a las personas que trabajan en los medios. Su objetivo es mejorar la calidad del periodismo, contribuir a una mejor comprensión de los medios y fomentar la libertad de prensa y la responsabilidad de los medios. Nació en 2004, como una red de varios socios europeos, coordinados por la Universidad de Lugano y la Universidad de Oxford. Fue diseñado para observar las tendencias en el periodismo y en los medios de comunicación, desde una perspectiva ética y deontológica muy amplia. Desde entonces, sus artículos, investigaciones y editoriales son publicados en las distintas páginas web de cada socio: https://es.ejo-online.eu/red-ej

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Prevención y recuperación de la tendinopatía rotuliana en jugadores de baloncesto

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    El baloncesto es una modalidad deportiva de gran exigencia física, por lo que supone un estrés muy elevado para el cuerpo del deportista, y a menudo conduce a lesiones relacionadas con el sobreuso o el contacto con el suelo u otro jugador. De promedio casi la mitad de los jugadores de un equipo de baloncesto tiene alguna lesión durante el transcurso de una temporada y en algunos casos múltiples. En cualquier temporada, la incidencia de lesiones puede ser el mayor condicionante en el número de victorias y derrotas. La tendinopatía rotuliana es una lesión por sobre uso muy común en el baloncesto, el tendón rotuliano es vulnerable a las caídas repetitivas y actividades que conllevan cambios de dirección constantes. El aumento exponencial del número de participantes y el nivel de intensidad en el baloncesto ha supuesto paralelamente un aumento del número de lesiones en todos los niveles, así como una mayor investigación en la prevención y recuperaciones de lesiones. La tendinopatía rotuliana es la segunda lesión más habitual en el baloncesto, únicamente por detrás de los esguinces de tobillo. Existen numerosos estudios científicos que hablan sobre distintos tratamientos y protocolos de recuperación, sin embargo no hay un consenso sobre cuál es el protocolo ideal para su recuperación. Con este trabajo trataré de determinar cuál o cuáles son los protocolos más adecuados para prevenir y tratar esta patología teniendo en cuento la tipología de esfuerzos característicos del baloncesto

    Desarrollo de las aplicaciones didácticas de un generador eólico de 600 W en un laboratorio de energías renovables para titulaciones de Ingeniería

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    El proyecto se ha desarrollado en la Escuela Politécnica Superior de la Universidad de Burgos, en esta escuela trabajan los ocho componentes del equipo, miembros del departamento de Física. El objetivo esencial de este proyecto es mostrar a los estudiantes la bondad del uso de las energías renovables y en particular el de la energía eólica. El desarrollo de esta fuente de energía precisa de una cuidadosa experimentación que no sólo refuerce los conceptos, sino que además demuestre la viabilidad de la misma y su forma de utilizarla. Para alcanzar este objetivo se ha adquirido un aerogenerador del tipo 'inclin' de seiscientos watios, junto con un sistema de regulación y almacenamiento y una estación meteorológica. Tanto el aerogenerador como la estación se han instalado en la terraza de la escuela politécnica. Mediante una conducción eléctrica las terminales de los sitemas se conectan al sistema de regulación y control y a un ordenador instalado en el laboratorio de alumnos del departamento, constituyendo junto con el sistema de almacenamiento por baterías, una de las prácticas de energía eólica del laboratorio de energías renovables. La evaluación de los trabajos de laboratorio que confeccionan los alumnos permitirá, una vez acabado el primer trimestre del curso, establecer el nivel de interés y comprensión de la energía eólica en operación real por parte de los mismos. Finalmente se está confeccionando un libro de prácticas de energías renovables para su publicación en la Universidad de Burgos.Junta de Castilla y León. Consejería de Educación y CulturaCastilla y LeónES

    3'UTR Polymorphism in ACSL1 Gene Correlates with Expression Levels and Poor Clinical Outcome in Colon Cancer Patients.

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    Strong evidence suggests that lipid metabolism (LM) has an essential role in tumor growth to support special energetic and structural requirements of tumor cells. Recently, overexpression of LM-related genes, apolipoproteins related to metabolic syndrome, and ACSL/SCD network involved in fatty acid activation have been proposed as prognostic markers of colon cancer (CC). Furthermore, activation of this latter lipid network has been recently demonstrated to confer invasive and stem cell properties to tumor cells promoting tumor aggressiveness and patient relapse. With the aim of elucidating whether any genetic variation within these genes could influence basal expression levels and consequent susceptibility to relapse, we genotype, in 284 CC patients, 57 polymorphisms located in the 7 genes of these lipid networks previously associated with worse clinical outcome of CC patients (ABCA1, ACSL1, AGPAT1, APOA2, APOC1, APOC2 and SCD), some of them related to CC aggressiveness. After adjusting with clinical confounding factors and multiple comparisons, an association between genotype and disease-free survival (DFS) was shown for rs8086 in 3'-UTR of ACSL1 gene (HR 3.08; 95% CI 1.69-5.63; adjusted p = 0.046). Furthermore, the risk T/T genotype had significantly higher ACSL1 gene expression levels than patients carrying C/T or C/C genotype (means = 5.34; 3.73; 2.37 respectively; p-value (ANOVA) = 0.019), suggesting a functional role of this variant. Thus, we have identified a "risk genotype" of ACSL1 gene that confers constitutive high levels of the enzyme, which is involved in the activation of fatty acids through conversion to acyl-CoA and has been recently related to increased invasiveness of tumor cells. These results suggest that rs8086 of ACSL1 could be a promising prognostic marker in CC patients, reinforcing the relevance of LM in the progression of CC
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