NLRP3 Inflammasome in Vascular Disease: A Recurrent Villain to Combat Pharmacologically

Despite the great advances in medicine, mortality from cardiovascular diseases keeps on growing. This tendency is not likely to change considering the pandemic proportions of obesity and diabetes. Besides, the global population is more aged as life expectancy increases, and vascular aging plays a key role in the increased risk of vascular disease. In light of recent trials, namely the CANTOS study, showing the enormous potential of anti-inflammatory therapies and in particular those targeted to IL-1β, a change in therapeutical management of cardiovascular diseases is coming about. The NLRP3 inflammasome is a multiprotein complex that assembles to engage the innate immune defense by processing the maturation of pro-inflammatory cytokines IL-1β and IL-18. Substantial evidence has positioned the NLRP3 inflammasome at the center of vascular disease progression, with a particular significance in the context of aging and the low-grade chronic inflammation associated (inflammaging). Therefore, pharmacological blockade of the NLRP3 inflammasome and its end products has arisen as an extremely promising tool to battle vascular disease. In this review, we discuss the mechanisms by which the NLRP3 inflammasome contributes to vascular disease, with particular attention to the consequences of aging, and we enumerate the therapeutic options available to combat this recurrent villainWork revised coming from the manuscript’s co-authors has been supported by funding from Plan Nacional I+D [PID2020-115590RB-100/AEI/ 10.13039/501100011033] to C.P. and C.F.S-F and Talent Advanced Researchers’ Grant from Comunidad Autónoma de Madrid (2019-T1/IND13794) to F.C.; I.V. is supported by an FPU-MECD fellowship (FPU16/02612); L.S. is supported by an FPI-UAM fellowship (SFPI/2020-0053

Effect of the application of edible coatings on quality and phytochemical compounds of pre-cut papaya

[SPA] El procesado mínimo de frutas se ha convertido en un objetivo importante para productores e industrias transformadoras de frutas debido a la creciente demanda de alimentos frescos, saludables y listos para ser consumidos. En el presente estudio se ha evaluado el efecto de la aplicación de recubrimientos comestibles (RCs) sobre los parámetros de calidad y compuestos fitoquímicos de papaya pre-cortada. La composición de los RC fue: almidón (4%), glicerol (2%), ácido cítrico (5%) y lactato cálcico (2,5 %), estudiándose el efecto de la presencia (2,2 g/l) o ausencia de aceite esencial de canela (AEC) en el recubrimiento. Los trozos de papaya recubiertos se envasaron en bolsas de polietileno de baja permeabilidad al oxígeno, bajo atmósfera de nitrógeno y se almacenaron durante 15 días a 4 ºC. Durante el almacenamiento se determinaron color, firmeza, acidez titulable, pH, sólidos solubles y totales, vitamina C y fenoles totales. No se observaron diferencias significativas (P<0,05) en los parámetros de color (ΔE) estudiados entre la papaya recubierta sin AEC y la papaya sin recubrir. La firmeza disminuyó no significativamente en la papaya recubierta a lo largo del tiempo de conservación refrigerada. El recubrimiento dio lugar a un descenso significativo del pH. Durante la conservación frigorífica, el pH aumentó en papaya recubierta, siendo significativamente mayor en las muestras sin AEC. Las variaciones en el pH se correlacionaron negativamente con la acidez. Ni el tiempo de almacenamiento ni los RCs afectaron significativamente al contenido en sólidos solubles y sólidos totales de la papaya pre-cortada. El contenido en vitamina C fue significativamente mayor en la papaya recubierta que en la no recubierta durante 11 días a 4 ºC. El contenido en fenoles aumentó significativamente hasta un máximo el primer día de almacenamiento para la papaya sin recubrir y la recubierta sin AEC. Sin embargo, en las muestras con AEC se observó un aumento gradual de fenoles totales durante el almacenamiento, alcanzando al final del mismo un contenido significativamente mayor que en las muestras sin recubrir y que en las recubiertas sin AEC. El recubrimiento compuesto por almidón (4%), glicerol (2%), ácido cítrico (5%), lactato cálcico (2,5 %) y aceite esencial de canela (2,2 g/l) permitió garantizar la calidad y la estabilidad de vitamina C total y fenoles totales de la papaya pre-cortada envasada en atmósfera de nitrógeno durante 11 días a 4 ºC. [ENG] Minimal processing of fruits has become an important goal for the fruit processing industry due to the increasing demand of fresh, healthy and ready-to-eat foods. The effect of the application of edible coatings on quality parameters and phytochemicals of pre-cut papaya was evaluated in the present work. Edible coating composition was: starch (4%), glicerol (2%), citric acid (5%), calcium lactate (2.5%). The addition of cinnamon essential oil (CEO) (2.2 g/l) to the coat was also studied. Pre-cut papaya was coated and packaged in polyethylene bags of low permeability to oxygen under nitrogen atmosphere, and was stored for 15 days at 4 ºC. Colour, firmness, titratable acidity, pH, soluble solids, total solids, vitamin C and total phenolics were analyzed during storage. Colour parameters (ΔE) differences between coated papaya without CEO and non-coated papaya were not significantly (P<0.05). Coated papaya firmness decreased not significantly during storage. Coating decreased significantly papaya pH value. During refrigerate storage, pH of coated papaya increased, with higher variations in coated papaya with AEC. The pH changes were negatively correlated with titratable acidity. Neither soluble solids nor total solids were significantly affected by storage time and edible coating. During storage, vitamin C content was lower in uncoated papaya than in coated papaya. Phenolic content reached a maximum the first day of storage in non-coated pre-cut papaya and in that coated without CEO, but phenolics significantly increased during storage in samples coated with CEO. The edible coating composed by starch (4%), glycerol (2%), citric acid (5%), calcium lactate (2.5%) and cinnamon essential oil (CEO) (2.2 g/l) guaranteed the quality and the stability of vitamin C and total phenolic of pre-cut papaya packaged under nitrogen atmosphere for 11 days at 4 ºC.Este trabajo ha sido financiado a través del proyecto RTA04-171-C2-2 del Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) (España) y del Proyecto CYTED XI.22. P. Elez-Martínez agradece al Ministerio de Educación y Ciencia (España) su contratación dentro del Programa Juan de la Cierva

Genome-Wide Expression in Visceral Adipose Tissue from Obese Prepubertal Children

Characterization of the genes expressed in adipose tissue (AT) is key to understanding the pathogenesis of obesity and to developing treatments for this condition. Our objective was to compare the gene expression in visceral AT (VAT) between obese and normal-weight prepubertal children. A total of fifteen obese and sixteen normal-weight children undergoing abdominal elective surgery were selected. RNA was extracted from VAT biopsies. Microarray experiments were independently performed for each sample (six obese and five normal-weight samples). Validation by quantitative PCR (qPCR) was performed on an additional 10 obese and 10 normal-weight VAT samples. Of 1276 differentially expressed genes (p < 0.05), 245 were more than two-fold higher in obese children than in normal-weight children. As validated by qPCR, expression was upregulated in genes involved in lipid and amino acid metabolism (CES1, NPRR3 and BHMT2), oxidative stress and extracellular matrix regulation (TNMD and NQO1), adipogenesis (CRYAB and AFF1) and inflammation (ANXA1); by contrast, only CALCRL gene expression was confirmed to be downregulated. In conclusion, this study in prepubertal children demonstrates the up- and down-regulation of genes that encode molecules that were previously proposed to influence the pathogenesis of adulthood obesity, as well as previously unreported dysregulated genes that may be candidate genes in the aetiology of obesity.This work was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I + D + I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (FONDOS FEDER) Projects no PI 020826 and PI051968 and Redes temáticas de investigación cooperativa RETIC (Red SAMID RD12/0026/0015). CG-L is a recipient of a fellowship from Plan Propio UGR

Uso la plataforma H5P de creación de contenido interactivo como herramienta para la creación de un laboratorio de bioquímica virtual e interactivo

En este proyecto de innovación docente está diseñado para que el alumnado se acerque a un laboratorio de bioquímica virtual e interactivo y conozca los diferentes métodos y técnicas experimentales que se utilizan en ciertos análisis clínicos

Pharmacological Blockade of NLRP3 Inflammasome/IL1β-Positive Loop Mitigates Endothelial Cell Senescence and Dysfunction

The clinical relevance of IL-1β in chronic inflammation underlying atherosclerosis has been reinforced by recent evidence associating pharmacological inhibition of the cytokine with lower cardiovascular risk. Previously, we have demonstrated a direct involvement of IL-1β in endothelial senescence. Therefore, this can be a key mechanism contributing to the sterile inflammatory milieu associated with aging, termed inflammaging. In the present study, we have evaluated whether a positive feedback of IL-1β in the NLRP3 inflammasome via NF-κB could promote human endothelial senescence in vitro and murine endothelial dysfunction in vivo. Our results indicate that the NLRP3 inflammasome is pivotal in mediating the detrimental effects of IL-1β, showing that auto-activation is a crucial feature boosting endothelial cell senescence in vitro, which is paralleled by vascular dysfunction in vivo. Hence, the inhibitor of NLRP3 inflammasome assembly, MCC 950, was able to disrupt the aforementioned positive loop, thus alleviating inflammation, cell senescence and vascular dysfunction. Besides, we explored alternative NLRP3 inflammasome inhibitory agents such as the RAS heptapeptide Ang-(1-7) and the anti-aging protein klotho, both of which demonstrated protective effects in vitro and in vivo. Altogether, our results highlight a fundamental role for the hereby described NLRP3 inflammasome/IL-1β positive feedback loop in stress-induced inflammaging and the associated vascular dysfunction, additionally providing evidence of a potential therapeutic use of MCC 950, Ang-(1-7) and recombinant klotho to block this loop and its deleterious effectsThis work has been supported by funding from 1) Plan Nacional I+D (PID2020-115590RB100/AEI/ 10.13039/501100011033) to C.P. and C.F.S-F; 2) Talent Advanced Researchers' Grant from Comunidad Autónoma de Madrid (2019-T1/IND-13794) to F.C., and 3) FONDECYT 1130300 to G.D.A. P.D. is recipient of a European social fund and Comunidad Autónoma de Madrid fellowship (PEJ-2018-AI/SAL-9955). I.V. is supported by an FPU-MECD fellowship (FPU16/02612

Bioprospección y diversidad química

17 páginas, 13 tablas y 73 esquemas de compuestos orgánicosUna de las herramientas necesarias para la conservación y el aprovechamiento sostenible de la biodiversidad botánica es el conocimiento de su valor añadido. El contenido en productos naturales bioactivos de las plantas se conoce desde la antigüedad por su valor medicinal y plaguicida. Sin embargo, aún existe un gran desconocimiento de la diversidad química del planeta, agravado por la presión humana sobre la biodiversidad y la consecuente desaparición de especies. Aquí vamos a presentar una pequeña muestra de diversidad química, su valor añadido y posibles soluciones a su aprovechamiento sostenible.Centro de Ciencias Medioambientales- CSIC MadridInstituto de Productos Naturales y Agrobiología - CSIC La Laguna-TenerifeUDI-Fitopatología Fac de Biología - La Laguna-TenerifePeer reviewe

Prevention of sexual violence through research as a pedagogical strategy in basic education

La violencia sexual es una problemática de salud pública que viene en aumento, convirtiéndose en un flagelo nacional, presentándose especialmente al interior del núcleo familiar, pero se manifiesta también en las diversas instituciones del colectivo social. El estudio busco prevenir la violencia sexual mediante la investigación como estrategia pedagógica en educación básica. Se guio bajo el enfoque de Investigación como estrategia pedagógica. Donde se utilizaron herramientas como diario de campo y observación participante. La unidad de análisis estuvo conformada por cuarenta (40) estudiantes de la IED Francisco de Paula Santander, Sede Simón Bolívar de Fundación-Magdalena. Los resultados evidenciaron que los alumnos no tenían conocimientos previos sobre violencia sexual, luego de la integración de la IEP al aula de clase desde el área de sociales se logró la apropiación y socialización de los conocimientos adquiridos a través del proceso de indagación por parte de los estudiantes con el apoyo docente.Sexual violence is a problem of public health that is increasing, becoming a national scourge, appearing especially within the family nucleus, but also manifested in the various institutions of the social collective. The study sought to prevent sexual violence through research as a pedagogical strategy in basic education. It was guided under the Research approach as a pedagogical strategy. Where tools were used as field diary and participant observation. The analysis unit consisted of forty (40) students of the IED Francisco de Paula Santander, Simón Bolívar campus of Fundación- Magdalena. The results showed that the students did not have previous knowledge about sexual violence, after the integration of the IEP into the classroom from the social area, the appropriation and socialization of the acquired knowledge was achieved through the process of inquiry by the students. students with teacher support

Guía para la elaboración de trabajos académicos de investigación

Prólogo. Guía de Buenas Prácticas. Guía para la elaboración del TFG del Grado en Estudios Árabes e Islámicos. Guía para la elaboración del TFG del Grado en Estudios Franceses. Guía para la elaboración del TFG del Grado en Estudios Ingleses. Guía para la elaboración del TFG del Grado en Filología Clásica. Guía para la elaboración del TFG del Grado en Filología Hispánica. Guía para la elaboración del TFG del Grado en Historia. Guía para la elaboración del TFG del Grado en Humanidades. Guía para la elaboración del TFG del Grado en Lingüística y Lenguas Aplicadas.Se trata de un manual de ayuda, que consta de una guía de buenas prácticas y de una guía académica, que fijan unos criterios objetivos para la preparación del TFG por parte del estudiante, que orientan al tutor/director en el desarrollo del trabajo y que sirven de punto de partida a la comisión evaluadora que finalmente tendrá que valorarlo.Este documento es una obra derivada de la Actuación Avalada para la Mejora Docente, Formación del Profesorado y Difusión de Resultados (modalidad A, UCA/R099REC/2013), “Guía Académica y de Buenas Prácticas para la realización de los TFG de los planes de estudio de grado de la Facultad de Filosofía y Letras” (Ref. AAA_14_043), financiado por la de la Unidad de Innovación Docente del Vicerrectorado de Docencia y Formación de la Universidad de Cádiz durante el curso académico 2013-2014.Formato PDF. 225 páginas

Gene signatures of early response to anti-TNF drugs in pediatric inflammatory bowel disease

T. Around a 20–30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged &lt;18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders (n = 27) and non-responders to anti-TNF therapy (n = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2−∆∆Ct method. Before initiation and after 2 weeks of treatment the expression of SMAD7 was decreased in patients who were considered as non-responders (p value &lt; 0.05). Changes in expression were also observed for TLR2 at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of DEFA5 decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the SMAD7 gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. TLR2 and DEFA5 need to be validated in larger studies.This work was funded by Instituto de Salud Carlos III (grants numbers PI16/00559 and PI19/00792), Consejería de Educación y Deporte de la Comunidad de Madrid (grant number PEJ16/MED/AI-1260), and by the Gregorio Marañón Health Research Institute (grant number PRE-2018-2), The study was cofunded by ERDF Funds (FEDER) from the European Commission, “A way of making Europe

Diseño de la asignatura de Bioquímica del Grado de Fisioterapia: elaboración de materiales para el aprendizaje a través de la clase invertida

Sección Deptal. de Bioquímica y Biología Molecular (Medicina)Fac. de MedicinaFALSEsubmitte