Nutraceutical Properties of Polyphenols against Liver Diseases

Current food tendencies, suboptimal dietary habits and a sedentary lifestyle are spreading metabolic disorders worldwide. Consequently, the prevalence of liver pathologies is increasing, as it is the main metabolic organ in the body. Chronic liver diseases, with non-alcoholic fatty liver disease (NAFLD) as the main cause, have an alarming prevalence of around 25% worldwide. Otherwise, the consumption of certain drugs leads to an acute liver failure (ALF), with drug-induced liver injury (DILI) as its main cause, or alcoholic liver disease (ALD). Although programs carried out by authorities are focused on improving dietary habits and lifestyle, the long-term compliance of the patient makes them difficult to follow. Thus, the supplementation with certain substances may represent a more easy-to-follow approach for patients. In this context, the consumption of polyphenol-rich food represents an attractive alternative as these compounds have been characterized to be effective in ameliorating liver pathologies. Despite of their structural diversity, certain similar characteristics allow to classify polyphenols in 5 groups: stilbenes, flavonoids, phenolic acids, lignans and curcuminoids. Herein, we have identified the most relevant compounds in each group and characterized their main sources. By this, authorities should encourage the consumption of polyphenol-rich products, as most of them are available in quotidian life, which might reduce the socioeconomical burden of liver diseases.We thank University of Basque Country (UPV/EHU), Basque Government and Asociacion Espanola Contra el Cancer (AECC) for the Pre-doctoral grants to M.C.-A., N.G.-U. and M.S.-M., respectively. Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)

Wnt-3a Induces Epigenetic Remodeling in Human Dental Pulp Stem Cells

Dental pulp stem cells (DPSCs) from adult teeth show the expression of a very complete repertoire of stem pluripotency core factors and a high plasticity for cell reprogramming. Canonical Wnt and Notch signaling pathways regulate stemness and the expression of pluripotency core factors in DPSCs, and even very short-term (48 h) activations of the Wnt pathway induce a profound remodeling of DPSCs at the physiologic and metabolic levels. In this work, DPSC cultures were exposed to treatments modulating Notch and Wnt signaling, and also induced to differentiate to osteo/adipocytes. DNA methylation, histone acetylation, histone methylation, and core factor expression levels where assessed by mass spectroscopy, Western blot, and qPCR. A short-term activation of Wnt signaling by WNT-3A induced a genomic DNA demethylation, and increased histone acetylation and histone methylation in DPSCs. The efficiency of cell reprogramming methods relies on the ability to surpass the epigenetic barrier, which determines cell lineage specificity. This study brings important information about the regulation of the epigenetic barrier by Wnt signaling in DPSCs, which could contribute to the development of safer and less aggressive reprogramming methodologies with a view to cell therapy.This work was funded by the UPV/EHU (GIU16/66, UFI 11/44; to F.U.), the Basque Government (GV/EJ; Ikerketa Taldeak IT831-13; to G.I. and ELKARTEK KK-2019-00093; to F.U.) and ISCIII (DTS18/00142; to N.S.)

Variables psicológicas implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción

El proyecto titulado: Variables implicadas en la actitud e iniciativa emprendedora (II): personalidad, cognición y emoción, es la continuidad de otro presentado en la convocatoria anterior (2016-2017) cuyo objetivo era evaluar variables psicológicas en la actitud emprendedora de los estudiantes universitarios de la Universidad Complutense de Madrid (UCM). Este segundo proyecto ha tenido por objetivo principal ampliar la evaluación a otras facultades y áreas de conocimiento de nuestra universidad a fin de obtener el mapa y perfil de la iniciativa emprendedora del universitario UCM

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.info:eu-repo/semantics/publishedVersio

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Role of VEGFC C-terminal fragment in colorectal cancer with metastatic capacity.

Los capítulos 3, 4,5,6 y 7 están sujetos a confidencialidad por la autora. 104 p.En el siglo XXI, el cáncer se ha convertido en la segunda causa de muerte en todo el mundo. Esta enfermedad es el resultado de un conjunto de mutaciones, provocando que las células crezcan, se dividan y se propaguen sin control, dando lugar a que se desarrolle metástasis.El cáncer colorrectal, (CCR) el cual se puede originar tanto en el colon como en el recto, se encuentra entre los cánceres con mayor mortalidad a nivel mundial. Varias investigaciones han demostrado que en el CCR existen bucles autocrinos, que juegan un papel importante en la iniciación y progresión del cáncer. Los factores de crecimiento están involucrados en esta estimulación autocrina, entre ellos cabe destacar los miembros de la familia del factor de crecimiento endotelial vascular (VEGF), aunque al principio se creía que su función solo se limitaba a la permeabilidad vascular y la angiogénesis de manera paracrina.El presente trabajo se ha centrado en el estudio de VEGF-C, ya que se ha demostrado su importante implicación en el microambiente tumoral del CCR. Además, nuestro laboratorio estudia las proteínas convertasas, las cuales son necesarias para para la maduración y activación del VEGFC. Las convertasas concretamente cortan entre el C-terminal silk homology domain (SHD) y el VEGF homology domain(VHD), desprendiendo el fragmento C-terminal.Hasta la fecha, se creía que el fragmento C-terminal liberado durante la escisión pro-VEGF-C no tenía ninguna función, pero hemos dedicado nuestro esfuerzo a dilucidar su papel en el CCR; siendo este el objetivo de la presente tesis. Para ello hemos realizado una serie de experimentos tanto in vitro como in vivo que han demostrado que el fragmento C terminal del VEGFC muestra características protumorales que le presentan como una diana para el CRC

Fomentando la educación para la sostenibilidad en la formación de maestros a través de espacios verdes -Huerto Didáctico y Real Jardín Botánico- como recursos educativos

El presente documento es la memoria del proyecto de innovación docente "Fomentando la educación para la sostenibilidad en la formación de maestros a través de espacios verdes -Huerto Didáctico y Real Jardín Botánico- como recursos educativos". En dicha memoria se especifican los objetivos propuestos, esto es que los/as alumnos/as adquieran conocimientos vinculados con la biología y la ecología, así como competencias transversales como el pensamiento reflexivo y valores democráticos y de sostenibilidad trabajando en espacios verdes. Se reportan las actividades realizadas en el Huerto Didáctico de la Facultad de Educación-CFP de la UCM y en el Real Jardín Botánico Alfonso XIII para la consecución de esos objetivos, concluyendo que los alumnos son capaces de aprender sobre la materia y ejecutar tareas de cuidado hortícola, a la vez que conectar con el medio natural cuando llevan a cabo actividades en los espacios verdes de la UCM

The immunogenetic diversity of the HLA system in Mexico correlates with underlying population genetic structure

International audienc

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols