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

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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

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

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Desarrollo y aplicación de métodos analíticos para la caracterización y mejora de semillas y aceites vegetales

Uno de los principales objetivos de la mejora genética de las plantas oleaginosas es el aumento del contenido y de la calidad del aceite de sus semillas. La calidad de los aceites vegetales se puede evaluar con referencia tanto a sus propiedades nutricionales como a sus propiedades funcionales, y no existe una calidad óptima de un aceite ya que esta depende de su uso específico. Los principales parámetros que determinan dichas propiedades son la composición de ácidos grasos y la presencia de componentes minoritarios como tocoferoles y fitoesteroles. De acuerdo con lo mencionado, la mejora genética de las plantas oleaginosas se basa en la modificación de la composición del aceite en dichos componentes y requiere la evaluación de la variación existente en colecciones de germoplasma de las distintas especies y de la obtenida por mutagénesis, así como de la evaluación de poblaciones segregantes en los programas de mejora. Esto supone el análisis de un número elevado de muestras de las que se dispone una cantidad muy pequeña. Un requisito indispensable para esta evaluación, es el desarrollo de métodos rápidos, fiables y no destructivos. El objetivo principal de esta tesis ha sido el desarrollo y puesta a punto de nuevos métodos de análisis aplicables a componentes de calidad del aceite en distintas semillas oleaginosas. En particular: 1.- En esta tesis se ha desarrollado y validado un método para el análisis de fitoesteroles en muestras pequeñas de semillas de girasol, lo cual es óptimo para estudios genéticos y mejora genética en los que la extracción de aceite no es factible. Los resultados han revelado gran variación de contenido en fitoesteroles en semillas de girasol, con un rango de variación desde 1426,0 hasta 4710,0 mg / kg de semilla y 2.855,2 a 9.752,0 mg/kg aceite. 2.- Se ha puesto a punto un método basado en la técnica de NIRS y análisis discriminante lineal para la discriminación entre semillas con alto contenido en oleico de semillas con alto contenido en ricinoleico. Dicha discriminación se basa principalmente en las regiones espectrales alrededor de 1400 y 1914 nm, principalmente asociadas con la absorbancia del grupo OH presente en el ácido ricinoleico. 3.- Asimismo, se ha demostrado que la técnica NIRS puede ser utilizada con precisión para el análisis de contenido de aceite y la concentración de los ácidos oleico y linoleico en muestras de harina de almendras. El análisis de estos componentes, se basa principalmente en la región espectral de 2240 a 2380 nm. 4.- Finalmente, la investigación llevada a cabo en esta tesis ha revelado un nuevo aceite de cártamo con alto contenido en ácido oleico y γ-tocoferol con mayor estabilidad oxidativa que el aceite alto oleico convencional, con alto contenido en α-tocoferol, y, en consecuencia, es adecuado para aplicaciones tales como la fritura, biolubricación o biocombustibles.Peer Reviewe

Phytosterols in the seeds of wild sunflower species

Ingestion of phytosterols prevents intestinal absorption of cholesterol in humans and results in a lowering of serum cholesterol, which has stimulated the use of phytosterols as enriched food ingredients in functional foods. Sunflower seeds and oils are rich sources of phytosterols. The variation reported for these compounds in cultivated sunflower germplasm is low. As for many other traits, wild sunflower species may contain valuable unexplored variation for phytosterol content and profile. The objective of this research was to evaluate the variation for seed phytosterols in a set of 47 wild Helianthus species from the USDA-ARS collection. An impressive variation was identified for total phytosterol content (1017 to 4308 mg kg-1 seed) and proportion of individual phytosterols, particularly campesterol (5.1 to 16.3%), stigmasterol (3.1 to 23.9%), beta-sitosterol (35.1 to 72.3%), delta-5-avenasterol (1.9 to 20.5%), delta-7-stigmastenol (1.1 to 20.3%), and delta-7-avenasterol (0.3 to 10.6%). Some of the extremes of these ranges of variation have not been identified in cultivated sunflower. The feasibility of transferring genes determining interesting phytosterol traits to cultivated sunflower should be investigated.The work was supported by research project P07-AGR-03011 from Junta de Andalucía and EU FEDER funds.Peer Reviewe

Tocoferoles y fitoesteroles en semillas de girasol para consumo directo

[EN] Sunflower seeds for the human food market are derived from both oilseed-type cultivars, with black achenes and low hull proportion, and confectionery-type cultivars, with striped achenes and high hull proportion. The objective of this research was to evaluate tocopherol and phytosterol contents in the seeds of both types of cultivars. Five oilseed-type and seven confectionery-type cultivars were evaluated in replicated field trials in two locations of Morocco and Spain. Large variations were found in hundred-kernel weight (2.6 to 5.5 g), kernel oil content (42.7 to 67.5%), tocopherol content (203 to 397 mg kg -1 kernel), and phytosterol content (2179 to 3555 mg kg -1 kernel). Both types of cultivars did not differ for kernel weight, kernel oil content, or tocopherol and phytosterol profiles. However, oilseed-type cultivars had significantly greater average tocopherol and phytosterol contents, though confectionery-type cultivars with levels of tocopherols and phytosterols similar to the best oilseed-type cultivars were identified. The large variations in kernel tocopherol and phytosterol contents found in this research suggest that there is room for breeding for increased levels of these compounds in order to develop healthier sunflower cultivars for the human food market.[ES] Las semillas de girasol para consumo directo proceden tanto de cultivares oleaginosos, con aquenios negros y baja proporción de cáscara, como de cultivares de consumo di - recto, con aquenios de colores claros o rayados y elevada proporción de cáscara. El objetivo de este trabajo fue evaluar el contenido en tocoferoles y fitoesteroles en semillas de am - bos tipos de cultivares. Se evaluaron cinco cultivares oleagi - nosos y siete cultivares de consumo directo en ensayos de campo replicados en dos localidades de Marruecos y Espa - ña. Se identificó gran variación para peso de 100 semillas (aquenios descascarillados; 2.6 a 5.5 g), contenido en aceite en la semilla (42.7 a 67.5%), contenido en tocoferoles (203 a 397 mg kg –1 semilla), y contenido en fitoesteroles (2179 a 3555 mg kg –1 semilla). No se observaron diferencias entre ambos tipos de cultivares para peso de semilla, contenido de aceite en la semilla, o perfiles de tocoferoles y fitoesteroles. Sin embargo, los cultivares oleaginosos presentaron mayor contenido medio de tocoferoles y fitoesteroles, aunque se identificaron cultivares de consumo directo con niveles de estos compuestos similares a los mejores cultivares oleagi - nosos. La gran variación encontrada para contenido en toco - feroles y fitoesteroles sugiere la posibilidad de elevar los ni - veles de estos compuestos mediante mejora genética con el objetivo de desarrollar cultivares de girasol de consumo di - recto más saludables.The research was partially supported by the Consejo Superior de Investigaciones Científicas (CSIC), Spain and Centre National pour la Recherche Scientifique et Technique (CNRST), Morocco, project number 2007MA0059.Peer Reviewe

Performance and seed quality of Moroccan sunflower varieties and Spanish landraces used for confectionery and snack food

Sunflower seeds are one of the most important sources of vegetable oil in the world. Additionally, they are used for confectionery and snack food, as well as for bird and pet food. Sunflower germplasm used for food differs between Morocco and Spain. Whereas sunflower seeds used for food in Morocco are mainly obtained from oilseed-type cultivars with black achenes and low hull proportion, those used in Spain derive from confectionery-type cultivars with black and white striped achenes and high hull proportion. The objective of this research was to evaluate the performance and seed quality of Moroccan and Spanish sunflower germplasm used for food. Six cultivars from Morocco and six landraces from Spain were evaluated in replicated field trials in Aïn Taoujdate (Morocco) and Córdoba (Spain) in 2009. Seed yield, hundred-achene weight, hundred-kernel weight, achene oil content, kernel oil content, and fatty acid profile were measured. The results showed that confectionery-type and oilseed-type cultivars did not differ in seed yield, hundred-kernel weight and kernel oil content. Since confectionery-type cultivars from Spain performed similarly to local oilseed-type cultivars, they could be introduced to diversify the offer of in-shell sunflower seed snack in Morocco.The research was partially supported by Consejo Superior de Investigaciones Científicas (CSIC), Spain and Centre National pour la Recherche Scientifique et Technique (CNRST), Morocco, project number 2007MA0059.Peer Reviewe

Identification of high oleic castor seeds by near infrared reflectance spectroscopy

Castor oil contains a high proportion (>80%) of the unusual hydroxy fatty acid ricinoleic acid. Additionally, a mutant with high oleic acid content (>70%) has been developed. Both fatty acids differ in the presence of an OH group in the C18 tail (ricinoleic acid). The objective of this research was to evaluate whether near-infrared reflectance spectroscopy (NIRS) can be used to discriminate between high oleic and high ricinoleic acid seeds. Eight hundred and seventy-two individual seeds collected in 2008, 688 high ricinoleic and 184 high oleic, were scanned by NIRS and further analyzed by GLC. As high oleic/low ricinoleic acid content is recessive and no intermediate fatty acid levels occur, the spectral data was subjected to linear discriminant analysis, which correctly classified all the seeds. The discriminant function was validated with a set of 637 seeds collected in 2009 from segregating populations, which were correctly classified in all cases. NIRS discrimination between oleic and ricinoleic acid was mainly based on spectral regions around 1,400 and 1,914 nm, putatively associated with the absorbance of the OH group. The results confirmed that NIRS provides an effective means of discriminating between high oleic and high ricinoleic acid seeds. © AOCS 2011.The research was funded by Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Research Project P08-AGR03962 “Oilseeds with special triacylglycerols” and European Union FEDER funds.Peer Reviewe