Articles publicats (Medicina Experimental)
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- ItemOpen AccessLeisure-Time Physical Activity on Age-Modelled Trajectories of Body Mass Index and Obesity Risk Throughout Life: Multivariable Regression and Mendelian Randomization Analyses Using Electronic Health Record Data From the CORDELIA-Catalunya Study(John Wiley & Sons Ltd, 2026) Hernando-Redondo, Javier; Camps-Vilaró, Anna; Elosua, Roberto; Fornara, Eleonora; Bermúdez López, Marcelino; Torán-Monserrat, Pere; Jiménez-Navarro, Ainara; Valdivielso, José M; López-Lifante, Víctor M; Salas-Fernández, Tomàs; Cambray Carner, Serafí; Cruz, Raquel; Marrugat, Jaume; Hernáez, ÁlvaroAims: To assess whether self-reported leisure-time physical activity, moderate-to-vigorous leisure-time physical activity, and genetically determined cardiorespiratory fitness are associated with age-related BMI trajectories and incident obesity. Methods: We pooled 14 993 adults (30-90 years; 52.7% women; cohorts: REGICOR-ACRISC, ILERVAS, ARTPER) with estimated LTPA (moderate-to-vigorous LTPA [MVLTPA] in REGICOR-ACRISC), genotype, and 120 352 repeated BMI measurements from electronic health records (1990-2024). LTPA was categorised into cohort-specific quartiles; MVLTPA in 0, < 100, < 200, and ≥ 200 METs-min/day. In one-sample Mendelian randomisation analyses, we categorised participants in quartiles of a cardiorespiratory fitness polygenic risk score derived from a large GWAS in UK Biobank. Group-dependent BMI trajectories were modelled using spline mixed-effects models. Obesity onset (first BMI ≥ 30 kg/m2) was analysed with IPW-weighted Kaplan-Meier curves and Cox models. Results: Higher LTPA was associated with slower BMI increases in ages 30-60 (Q1: +0.120 vs. Q4: +0.075 kg/m2·year), slower declines in ages 70-90 (Q1: -0.143 vs. Q4: -0.123 kg/m2·year), and lower obesity risk (Q4 vs. Q1: HR 0.83, 95% CI 0.72-0.96). Similar trends were observed for MVLTPA. Higher genetically determined cardiorespiratory fitness showed parallel gradients (ages 30-60, Q1: +0.109 vs. Q4: +0.101 kg/m2·year; ages 70-90, Q1: -0.130 vs. Q4: -0.102 kg/m2·year) and lower obesity risk (Q4 vs. Q1: HR 0.66, 0.56-0.78). Associations were present for women and men separately, but were stronger in men. Conclusions: Higher LTPA and MVLTPA were associated with more favourable lifelong BMI trajectories, delayed obesity risk, and convergent support from Mendelian randomisation analyses, supporting a causal protective role of physical activity (in both sexes but stronger in men).
- ItemOpen AccessRecomendaciones para el uso apropiado de anticuerpos antiamiloide en el tratamiento de la enfermedad de Alzheimer del Grupo de Conducta y Demencias de la Sociedad Española de Neurología(Elsevier, 2026) Sánchez-Valle, R.; Alcolea, D.; Amer Ferrer, G.; Balasa, M.; Casado Naranjo, I.; Fortea, J.; Lladó, A.; Lleó, A.; Montes, A. M.; Martinez Lozano, L.; Martínez-Lage, P.; Matias-Guiu, Xavier; Mendioroz, M.; Perez Martinez, D. A.; Piñol Ripoll, Gerard; Riverol, M.; Sanchez-Juan, P.; Bondía, H. V.Introducción Dos anticuerpos monoclonales dirigidos contra Aβ (mAbs antiamiloide) han sido recientemente aprobados en la Comisión Europea para la enfermedad de Alzheimer (EA). En este contexto, el Grupo de Estudio (GE) de Conducta y Demencias de la Sociedad Española de Neurología se propuso realizar un documento con recomendaciones de buen uso de mAbs antiamiloides escrito por neurólogos expertos nacionales. El objetivo complementar las indicaciones de las agencias reguladoras con recomendaciones sobre aspectos prácticos de aplicación en nuestro medio. Desarrollo Cincuenta y siete miembros del GE participaron en el documento (enero-septiembre del 2025) que incluye recomendaciones sobre criterios de selección y exclusión de candidatos, efectos adversos, monitorización, criterios de discontinuación, decisiones compartidas médico-paciente y requerimientos de los centros prescriptores. Todos los participantes fueron invitados a revisar el documento completo, a mostrar su acuerdo o discrepancia con cada una de las recomendaciones y a compartir comentarios. Conclusiones La introducción de los primeros mAbs antiamiloide suponen un cambio en el paradigma del manejo de la EA, no exento de dificultades. Los expertos participantes mostraron un alto consenso en aspectos operativos y clínicos básicos, siendo las áreas que generaron más debate los requerimientos de los centros prescriptores y la discontinuación de los mAbs antiamiloide. Los participantes revelaron preocupaciones sobre la equidad de acceso y el encaje en la asistencia actual, especialmente si no hay una adecuada dotación de recursos para su implementación. Este documento habrá de ser actualizado a medida que se disponga de nuevos conocimientos o/y se aprueben nuevos fármacos de esta clase.
- ItemOpen AccessScreening-based repurposing identifies potassium dehydroandrographolide succinate (KDAS) as a selective suppressor of TNF-α-induced caspase-8-dependent apoptosis in colonic epithelial cells(Nature Portfolio, 2026) Valero-Cortijo, Alvaro; Shoenenberger-Arnaiz, Joan Antoni; Yuste Mateos, Víctor J. (Víctor José); Ribas i Fortuny, JuditUnder physiological conditions, tumor necrosis factor-α (TNF-α) favors cell survival through cytoprotective checkpoints, including a FIP200-dependent non-canonical autophagy pathway. Disruption of this checkpoint shifts TNF-α signaling toward apoptosis, a process relevant to epithelial injury in inflammatory bowel disease (IBD). Anti-TNF-α biologics are standard IBD therapy but primarily neutralize extracellular TNF-α without reducing epithelial susceptibility to death. Here, we conducted a two-step screen of 2421 clinically approved compounds in TNF-α-challenged FIP200-deficient cells to identify drugs that restore cytoprotection. Potassium dehydroandrographolide succinate (KDAS) emerged as a top candidate and conferred > 85% cytoprotection in FIP200-deficient HCT116 cells by inhibiting TNF-α-induced, caspase-8-dependent apoptosis without affecting necroptosis. Other andrographolides did not confer cytoprotection, highlighting KDAS specificity. KDAS also suppressed TRAIL-induced apoptosis and protected additional human cell lines and primary human colonic epithelial cells. Although KDAS enhanced early NF-κB and ERK signaling, pharmacological inhibition of these pathways did not abrogate cytoprotection, suggesting that they are dispensable for its protective effect. These findings identify KDAS as a candidate cytoprotective compound capable of preserving epithelial cell viability downstream of TNF-α receptor activation and indicate a pharmacological approach to limit epithelial apoptosis in TNF-α-mediated diseases such as IBD.
- ItemOpen AccessFrom Lungs to Vascular Health: Airflow Obstruction, Not Lung Function Decline, Predicts Atherosclerosis Progression Independent of Smoking Status(Elsevier, 2026) Henríquez-Beltrán, Mario; Gracia-Lavedan, Esther; Sánchez-Cucó, Anna; Torres, Gerard; Targa, Adriano D. S.; Bermúdez López, Marcelino; Valdivielso, José Manuel; Pamplona Gras, Reinald; Mauricio, Dídac; Castro-Boqué, Eva; Fernández, Elvira; Lecube, Albert; de Batlle, Jordi; Barbé Illa, Ferran; González, JessicaObjectives: To prospectively evaluate the relationship between 4-year changes in lung function and the progression of subclinical atherosclerosis among 1623 middle-aged adults with at least one cardiovascular risk factor participating in ILERVAS, and to determine whether individuals who develop airflow obstruction (AO) are especially susceptible to accelerated atherosclerosis progression. Methods: This prospective cohort study included 1623 middle-aged adults from the ILERVAS cohort, recruited in primary care centers in the province of Lleida (Catalonia, Spain), with baseline assessments conducted between 2015 and 2018 and follow-up visits between 2019 and 2021 (mean follow-up, 3.99 [SD, 0.22] years). Pulmonary function was assessed by spirometry at baseline and at 4-year follow-up. Subclinical atherosclerosis was evaluated using vascular ultrasound of 12 carotid and femoral territories at baseline and at follow-up, with total plaque area quantified. Associations were analyzed using multivariable linear regression models, adjusting for clinical variables and baseline plaque burden. Analyses were stratified by smoking status. Results: Median annual declines were -95mL (-2.04%) for FVC and -78mL (-2.00%) for FEV1. Categorization of annual pulmonary function decline by tertiles showed no significant association with plaque progression. In contrast, incident AO was associated with greater annual FEV1 decline (-146.73 vs -74.90mL; P<.001) and with greater plaque burden, reflected by an increase in affected vascular territories (0.26 [IQR, 0.00-0.75]; P<.001). Multivariable models confirmed larger annual increases in total (4.40mm2; P<.001), carotid (2.33mm2; P<.001), and femoral (1.99mm2; P=.031) plaque areas among participants with incident AO, with consistent results across smoking strata. Sensitivity analyses using a lower limit of normal-based definition of AO showed similar findings, with effect estimates consistent with the primary fixed-ratio analyses. Conclusions: In this two-time-point analysis, lung function decline was not independently associated with subclinical atherosclerosis progression. In contrast, incident AO was consistently associated with greater plaque progression across smoking strata. These findings support incident AO as a spirometric marker associated with vascular risk.
- ItemOpen Access18:2 Cholesterol Ester is a Novel Prognostic Biomarker of Disease Progression in Multiple Sclerosis(Springer, 2026) Torres Cabestany, Pascual; Sánchez, Anna Gil; Sancho-Saldaña, Agustín; Quibus, Laura; San Pedro Murillo, Eduardo; Ruiz-Fernández, Emilio; Peralta, Silvia; Solana, Maria José; Brieva, Luis; González Mingot, CristinaMultiple sclerosis (MS) presents diverse clinical outcomes. Cholesterol esterification (CE) has been implicated as a disease mechanism involved in the remyelination process. We investigated whether cerebrospinal fluid (CSF) 18:2 cholesterol ester (18:2 CE) levels at diagnosis could predict 10-year MS progression. We aimed to determine if CSF 18:2 CE levels correlate with long-term disease progression. In a retrospective case-control single-centre study with 115 MS patients and 57 controls, we conducted targeted lipidomic analysis of CSF. Clinical data, oligoclonal bands, brain and spinal cord MRI, and CSF 18:2 CE levels were collected. Elevated CSF 18:2 CE levels were significantly associated with a higher risk of 10-year MS progression, with an AUC of 0.91 in a multivariable logistic regression model. Patients initially treated with a high-efficacy drug did not show a worse prognosis despite presenting elevated CE18:2 levels at the time of diagnosis. However, patients treated with a high-efficacy drug as a second or third option showed a positive correlation between CE18:2 levels and EDSS at 10 years. CSF 18:2 CE is a potential prognostic biomarker for predicting long-term MS progression, potentially indicating reduced remyelination capacity. These findings hold promise for improved patient management and warrant prospective validation.