Articles publicats (Medicina Experimental)
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- ItemOpen AccessMediterranean Diet Is a Predictor of Progression of Subclinical Atherosclerosis in a Mediterranean Population: The ILERVAS Prospective Cohort Study(MDPI, 2024) Rojo López, Marina Idalia; Bermúdez López, Marcelino; Castro, Eva; Farràs, Cristina; Torres, Gerard; Pamplona Gras, Reinald; Lecube Torelló, Albert; Valdivieso, José Manuel; Fernández, Elvira; Julve, Josep; Castelblanco Echavarría, Esmeralda; Alonso, Núria; Antentas, Maria; Barranco Altirriba, María; Perera-Lluna, Alexandre; Franch-Nadal, Josep; Granado Casas, Minerva; Mauricio Puente, Dídac; ILERVAS Project CollaboratorsAtherosclerotic cardiovascular disease remains a major health issue, often developing silently as subclinical atherosclerotic disease (SAD). The Mediterranean diet (MDiet) is known for its cardiovascular benefits, but the combined influence of both MDiet adherence and physical activity (PA) on SAD progression has not been previously documented. Objective: We aimed to investigate how adherence to a healthy lifestyle, defined as MDiet adherence and PA level, influences SAD progression in subjects from the ILERVAS cohort follow-up. Methods: A study on 3097 participants from the ILERVAS prospective cohort was conducted. MDiet adherence was assessed using the MEDAS score, and PA categories were established using the IPAQ, both categorized into low, moderate, and high levels. Two different lifestyle scores integrating the MDiet and PA categories were built. The presence of atherosclerotic plaques was assessed by carotid and femoral ultrasound examination. Demographic, clinical, and biochemical data were also obtained. Multivariable linear, logistic, and Poisson regression models adjusted for potential confounders were used to analyze the association between the lifestyle scores and SAD progression, as well as the MDiet and PA as separate variables and number of territories with plaque. Results: A healthier lifestyle score did not show an effect on SAD progression. However, a higher MEDAS score was associated with a 3% decrease in the number of territories with plaque (IRR 0.97, 95% CI 0.96–0.99, p < 0.001), suggesting a protective effect of the adherence to the MDiet. PA did not show a significant association (IRR 1.00, 95% CI 1.00–1.00, p = 0.269). Older age, hypertension, dyslipidemia, smoking, and lower eGFR were associated with SAD progression, while the female sex was protective (IRR 0.67, 95% CI 0.63–0.72, p < 0.001). Conclusions: The findings of this study show that higher adherence to the MDiet is associated with reduced incidence of SAD, indicating its potential role in cardiovascular prevention strategies. Although a higher lifestyle score or physical activity levels did not show any significant effect, promoting the MDiet, alongside managing traditional cardiovascular risk factors, could be an effective public health intervention to prevent atherosclerosis and reduce the burden of cardiovascular disease.
- ItemOpen AccessExposure of a cryptic Hsp70 binding site determines the cytotoxicity of the ALS-associated SOD1-mutant A4V(Oxford University Press, 2019) Claes, Filip; Rudyak, Stanislav; Laird, Angela S.; Louros, Nikolaos; Beerten, Jacinte; Debulpaep, Maja; Michiels, Emiel; van der Kant, Rob; Van Durme, Joost; De Baets, Greet; Houben, Bert; Ramakers, Meine; Yuan, Kristy; Gwee, Serene S. L.; Hernández i Estanyol, Sara; Broersen, Kerensa; Oliveberg, Mikael; Moahamed, Barbara; Kirstein, Janine; Robberecht, Wim; Rousseau, Frederic; Schymkowitz, JoostThe accumulation of toxic protein aggregates is thought to play a key role in a range of degenerative pathologies, but it remains unclear why aggregation of polypeptides into non-native assemblies is toxic and why cellular clearance pathways offer ineffective protection. We here study the A4V mutant of SOD1, which forms toxic aggregates in motor neurons of patients with familial amyotrophic lateral sclerosis (ALS). A comparison of the location of aggregation prone regions (APRs) and Hsp70 binding sites in the denatured state of SOD1 reveals that ALS-associated mutations promote exposure of the APRs more than the strongest Hsc/Hsp70 binding site that we could detect. Mutations designed to increase the exposure of this Hsp70 interaction site in the denatured state promote aggregation but also display an increased interaction with Hsp70 chaperones. Depending on the cell type, in vitro this resulted in cellular inclusion body formation or increased clearance, accompanied with a suppression of cytotoxicity. The latter was also observed in a zebrafish model in vivo. Our results suggest that the uncontrolled accumulation of toxic SOD1A4V aggregates results from insufficient detection by the cellular surveillance network.
- ItemOpen AccessPhenotypic upregulation of hexocylceramides and ether-linked phosphocholines as markers of human extreme longevity(Anatomical Society, 2024) Fernández Bernal, Anna; Sol, Joaquim; Galo-Licona, José Daniel; Mota Martorell, Natàlia; Mas-Bargues, Cristina; Belenguer-Varea, Ángel; Obis Monné, Èlia; Viña Ribes, José; Borrás, Consuelo; Jové Font, Mariona; Pamplona Gras, ReinaldCentenarians and their relatives possess a notable survival advantage, with higher longevity and reduced susceptibility to major age-related diseases. To date, characteristic omics profiles of centenarians have been described, demonstrating that these individuals with exceptional longevity regulate their metabolism to adapt and incorporate more resilient biomolecules into their cells. Among these adaptations, the lipidomic profile stands out. However, it has not yet been determined whether this lipidomic profile is specific to centenarians or is the consequence of extreme longevity genetics and is also present in centenarians' offspring. This distinction is crucial for defining potential therapeutic targets that could help delay the aging process and associated pathologies. We applied mass-spectrometry-based techniques to quantify 569 lipid species in plasma samples from 39 centenarians, 63 centenarians' offspring, and 69 noncentenarians' offspring without familial connections. Based on this profile, we calculated different indexes to characterize the functional and structural properties of plasma lipidome. Our findings demonstrate that extreme longevity genetics (centenarians and centenarians' offspring) determines a specific lipidomic signature characterized by (i) an enrichment of hexosylceramides, (ii) a decrease of specific species of ceramides and sulfatides, (iii) a global increase of ether-PC and ether-LPC, and (iv) changes in the fluidity and diversity of specific lipid classes. We point out the conversion of ceramides to hexosylceramides and the maintenance of the levels of the ether-linked PC as a phenotypic trait to guarantee extreme longevity. We propose that this molecular signature is the result of an intrinsic adaptive program that preserves protective mechanisms and cellular identity.
- ItemOpen AccessDay-to-Day Fluctuation in Micronutrient Content in Human Milk Relative to Maternal Diet(MDPI, 2024) Ureta Velasco, Noelia; Montealegre-Pomar, Adriana; Keller, Kristin; Escuder Vieco, Diana; Serrano Casasola, José Carlos Enrique; García Lara, Nadia Raquel; Pallás-Alonso, Carmen RosaBackground/Objectives: The impact of daily variations in habitual maternal intake on human milk (HM) composition has been poorly studied. We aimed to investigate the associations between day-to-day fluctuation in the micronutrient concentration in HM and daily maternal diet. Methods: To this end, an observational longitudinal study was carried out. A total of 143 lactating women each compiled a five-day weighed dietary record and concomitantly expressed milk for four successive days. Maternal daily intakes of micronutrients and food groups were analyzed. Free thiamine, free riboflavin, nicotinamide, pantothenic acid, pyridoxal, folic acid, cobalamin, ascorbic and dehydroascorbic acids, retinol, alpha- and gamma-tocopherol, cholecalciferol, and calcidiol in HM were determined for each of the four investigated days. A longitudinal data analysis with generalized estimating equation models was performed. Results: For each daily serving of meat, fish, and eggs, total vitamin D3 levels increased by 243.2 pg/mL (p = 0.027) and selenium levels increased by 0.16 ppb (p = 0.031) in HM. For every 1 mg/day of riboflavin supplementation, free riboflavin levels in HM increased by 28.6 mcg/L (p = 0.019). Pyridoxal levels in HM increased by 6.3 mcg/L per 1 mg/day of vitamin B6 supplementation (p = 0.001), and by 2 mcg/L per daily fruit ration (p = 0.016). Conclusions: In conclusion, we were able to quantify the impact of the usual day-to-day variations in the diet and in the intake of commonly used supplements on the fluctuation of vitamin D, free riboflavin, pyridoxal, and selenium concentration in the milk of lactating women.
- ItemOpen AccessEl papel de las facultades de medicina(Elsevier, 2024) Lara, J. Pablo; Compañ, Antonio; Casanovas i Llorens, AnnaLas facultades de medicina son los centros responsables del título de grado que habilita para el ejercicio de la profesión médica, regulada por la normativa europea y nacional. Su número ha pasado de 28 a 50 en los últimos 15 años, decisión que debería depender únicamente de criterios académicos y sanitarios. «Es necesario proporcionar a los futuros médicos la mejor formación científica, profesional y humana posible, para que sean capaces de solucionar los problemas de salud, en un itinerario coordinado y continuado que se inicia con el grado y la formación sanitaria especializada, seguida por un desarrollo profesional continuo» (Declaración de Málaga 2022, Estándares para la educación médica en el grado: pensando en el futuro, avalada por instituciones nacionales e internacionales). Tenemos que seguir trabajando de forma coordinada los responsables universitarios y sanitarios para estabilizar, promocionar y aumentar nuestro profesorado. Afrontamos retos, con deseos de mejorar, gracias a la dedicación de todas las personas que se forman y forman para cuidar la salud de los demás, con nuestro mayor agradecimiento.