Articles publicats (Medicina Experimental)
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- ItemOpen AccessRemote ischemic perconditioning and postconditioning reduced cerebral ischemic injury modulating inflammatory responses and metabolic pathways(Sage, 2026) Torres Querol, Coral; Pamplona Gras, Reinald; Arque, Gloria; Purroy Garcia, FranciscoRemote ischemic conditioning (RIC) mitigates ischemic injury through transient, repetitive vascular occlusion in a limb distant from the injury site. Although its protective effects are recognized, the underlying mechanisms remain incompletely understood. This study investigated the metabolic and inflammatory changes induced by RIC to identify novel cytoprotective targets. We used a mouse model of transient focal cerebral ischemia induced by 60-min occlusion of the distal middle cerebral artery. Two RIC protocols were applied: remote ischemic perconditioning (RIPerC), consisting of three cycles of 5-min hindlimb ischemia followed by 5-min reperfusion during ischemia, and remote ischemic postconditioning (RIPostC), applied after reperfusion. Plasma cytokines were quantified using a multiplex assay, and metabolomic profiles of plasma and brain samples were analyzed by untargeted liquid chromatography-mass spectrometry (LC-MS). Data were evaluated with univariate and multivariate statistical methods. RIC induced moderate changes in the brain metabolome but significantly increased three plasma metabolites: Cer (42:3), HexCer (36:1), and TG (28:0), suggesting systemic metabolic modulation during ischemia-reperfusion. Both RIPerC and RIPostC conferred neuroprotection, likely through regulation of peripheral immune responses. These findings demonstrate that RIPerC and RIPostC protect against ischemic injury by modulating inflammatory and metabolic pathways in systemic circulation and brain, providing insights into ischemic tolerance and biomarker discovery.
- ItemOpen AccessARID1A deficiency reprograms the tumor secretome, enhancing microenvironmental remodeling and metastatic dissemination in endometrial carcinoma(Springer Nature, 2026) Megino-Luque, Cristina; Albertí Valls, Manel; Olave, Sara; Sisó, Pol; Bonifaci, Núria; Macià Armengol, Anna, Anna; Matias-Guiu, Xavier; Gatius, Sònia; Llobet-Navas, David; Eritja Sánchez, NúriaLoss-of-function mutations in AT-rich interactive domain-containing protein 1 A (ARID1A), accompanied by reduced protein expression, are common in endometrial carcinoma (EC) and correlate with shorter progression-free survival. Alterations in the EC cells secretome play a critical role in shaping the tumor microenvironment (TME), thereby promoting disease progression, metastasis, and therapeutic resistance. Here, we demonstrate that ARID1A-deficient EC cells display a reprogrammed soluble secretome that alters tumor-stromal communication. Among the secreted factors, CXCL16 emerges as the predominant chemokine, promoting epithelial-to-mesenchymal transition and enhancing tumor cell invasiveness. Mechanistically, CXCL16 activates MAPK and Paxillin/FAK pathways, driving YAP/TAZ signaling and reinforcing pro-tumorigenic features. Elevated CXCL16 levels within the tumor niche also promote the conversion of stromal cells into cancer-associated fibroblasts (CAFs) in both preclinical models and patient samples of ARID1A-deficient EC. Importantly, genetic or pharmacological inhibition of CXCL16 or its receptor CXCR6 disrupts these pathogenic interactions, impairing EC cell migration and reducing metastatic burden. These findings identify the secretome of ARID1A-deficient EC cells as a key driver of tumor progression and underscore the CXCL16-CXCR6 axis as a promising therapeutic target in EC.
- ItemOpen AccessProteomic analysis in Alzheimer's disease and other dementias: a focus on sex-specific differences(BioMed Central, 2026) Comas-Albertí, Aina; Lladó, Albert; Esteller-Gauxax, Diana; Borrego-Écija, Sergi; Falgàs, Neus; Dakterzada, Farida; Pérez-Millan, Agnès; Puey, Roger; Collet-Romà, Tània; Guillén, Núria; Massons, Miquel; Tort-Merino, Adrià; Augé, Josep Maria; Fernandez-Villullas, Guadalupe; Bosch, Bea; Ruiz-García, Raquel; Naranjo, Laura; Balasa, Mircea; Piñol Ripoll, Gerard; Antonell, Anna; Sánchez-Valle, RaquelBackground: Fluid protein studies in cerebrospinal fluid (CSF) and plasma have provided important insights into neurodegenerative dementias; however, there is a limited investigation of sex-related differences and cross-biofluid relationships. In Alzheimer's disease (AD), Lewy body dementia (LBD), and frontotemporal dementia (FTD), large-scale, sex-stratified analyses of paired CSF and plasma samples remain scarce. Using the multiplex and ultrasensitive capabilities of NULISAseq™ technology, this study aims to characterize sex- and disease-specific proteomic alterations associated with Central Nervous System (CNS) pathology to explore underlying mechanisms. Methods: CSF and plasma samples from 359 individuals with AD, LBD, FTD, and cognitively healthy controls were analyzed using the NULISAseq™ CNS Disease Panel 120. Differential protein expression analyses were conducted across diagnoses and stratified by sex, adjusting for relevant covariates. Spearman's correlation analyses were performed to assess concordance between CSF and plasma protein levels. All statistical analyses were conducted in R v4.4.3. Results: Differential protein expression analyses across diagnoses revealed two potential transdiagnostic biomarkers: ICAM1 in CSF and ANXA5 in plasma, showing consistent increases across AD, LBD, and FTD. Sex-stratified analyses in CSF showed modest changes, including higher CCL26, ANXA5, and IL10 in females with AD, and higher IL9, PRDX6, and CX3CL1 in males with AD. In LBD, females exhibited upregulation of ACHE, SFRP1, POSTN in both CSF and plasma. NPTX1 was identified as a potential CSF biomarker for FTD, showing downregulation particularly in males. In contrast, analyses stratified by sex in plasma displayed a larger number of proteins across all dementias, with females showing a higher number of upregulated inflammation-related proteins predominantly involved in cytokine signaling. Overall cross-fluid correlations were restricted to a small subset of proteins, indicating compartment-specific regulation. Conclusions: This study represents a large-scale, sex-stratified proteomic analysis of CSF and plasma across major neurodegenerative dementias using NULISAseq™ technology. The findings highlight sex-dependent biomarker patterns, particularly in plasma, and underscore the importance of incorporating sex as a biological variable in dementia research. Future studies should validate candidate proteins in independent cohorts, investigate their functional and mechanistic roles, and assess their utility for biomarker development and sex-tailored therapeutic strategies.
- ItemOpen AccessAddressing persistent symptoms in post-COVID condition: Through a multimodal intervention delivered in two technology-based formats(SAGE Publications, 2026) Ariza, Mar; Cano, Neus; Carnes Vendrell, Anna; Gelonch Rosinach, Olga; Plana, Yemila; Porras-Garcia, Bruno; López-Soley, Elisabeth; Moron, Silvia; Piñol Ripoll, Gerard; Garolera, MaiteBackground: Persistent symptoms after acute COVID-19, formally recognized as post-COVID-19 condition (PCC), are prevalent and disabling. The World Health Organization has emphasized early, multidisciplinary rehabilitation using accessible and hybrid care models. However, no standard protocol currently exists, and few studies have evaluated digital formats in this context. Objective: To examine the effects of two digital rehabilitation formats-immersive virtual reality (IVR) and a self-guided online program-on cognitive and functional outcomes in individuals with PCC. Methods: The study used a nonrandomized, quasiexperimental pre-post design. We enrolled 172 adults with PCC into a 12-week multimodal program combining cognitive training, physical activity, and mindfulness; participants chose IVR or an online self-guided program, and usual-care controls were recruited at a separate site. Outcomes were assessed before and after across cognitive, psychological, lifestyle, functional, and quality-of-life domains. Results: Significant group-by-time interactions were observed across multiple domains. IVR was associated with improvements in global cognition, immediate recall, recognition memory, and response inhibition. The online intervention showed improvements in verbal recognition, mindfulness, and perceived health-related quality of life. Additional outcomes showed significant group-by-time interactions without postintervention differences, indicating differential trajectories over time rather than discrete between-group effects. Conclusions: Both IVR and online multimodal interventions were associated with domain-specific cognitive and functional benefits in individuals with PCC. These findings support the potential value of multicomponent rehabilitation approaches, while highlighting that some effects reflect differential trajectories rather than definitive postintervention group differences.
- ItemOpen AccessOutstanding improvement of the advanced lipoprotein profile in subjects with new-onset type 1 diabetes mellitus after achieving optimal glycemic control(Elsevier, 2021) Castelblanco Echavarría, Esmeralda; Hernández García, Marta; Ortega, Emilio; Amigó, Núria; Real, Jordi; Granado Casas, Minerva; Miñambres, Inka; López, Carolina; Lecube Torelló, Albert; Bermúdez López, Marcelino; Alonso, Núria; Julve, Josep; Mauricio Puente, DidacAims: The impact of glycemic optimization on lipoprotein subfraction parameters in apparently normolipidemic subjects with new-onset type 1 diabetes mellitus (T1D) was examined. Methods: We evaluated the serum lipid and advanced lipoprotein profiles in twenty subjects at onset of T1D and twenty non-diabetic controls by laboratory methods and 1H NMR spectroscopy shortly after diabetes diagnosis (baseline), and after achieving optimal glycemic control (HbA1c ≤ 7.0%). Results: Advanced lipoprotein analysis revealed a significant reduction from baseline in serum concentrations of triglycerides (TG), cholesterol (C), and apolipoprotein (Apo)B-containing lipoproteins of treated subjects (VLDL-TG: -21%, IDL-TG: -30%, LDL-TG: -34%, LDL-TG: -36%, P < 0.05; VLDL-C: -23%, IDL-C: -44%, LDL-C: -16%; p < 0.05). Decreased VLDL and LDL lipids were mainly attributed to concomitant reductions in the concentration of medium-sized VLDL (-36%) and medium-sized LDL (-31%) and, to a lesser extent, to large-sized LDL (-14%). Notably, proatherogenic IDL characteristics and related surrogates of atherogenicity were resolved upon achievement of optimal glycemic status. Moreover, the concentration of HDL-TG was also reduced (-18%) at follow-up. Conclusions: Our data showed that the achievement of optimal glycemic control after T1D onset corrected hidden derangements in ApoB-containing lipoproteins (particularly IDL) and HDL-TG that are related to higher cardiovascular risk in poorly controlled T1D.