IDIBAPS - Instituto de Investigaciones Biomédicas August Pi i Sunyer (Cataluña)

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12105/16961

El Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS) es un centro de investigación creado en 1993 que está integrado por el Departamento de Innovación, Universidades y Empresa (DIUE) de la Generalitat de Cataluña, por la Facultad de Medicina de la Universidad de Barcelona, el Hospital Clínico de Barcelona y el Instituto de Investigaciones Biomédicas de Barcelona del Consejo Superior de Investigaciones Científicas (IIBB-CSIC). El objetivo fundamental del IDIBAPS consiste en integrar la investigación clínica de calidad contrastada y la investigación básica de alto nivel. Se consigue así una transferencia más eficaz de los avances científicos obtenidos en prevención y tratamiento de los problemas de salud que predominan en nuestro país. Acreditado por el Instituto de Salud Carlos III como Instituto de Investigación Sanitaria en 2009, y renovando esta acreditación cada 5 años, forma parte así del total de 34 Institutos de Investigación Sanitaria acreditados existentes en la actualidad.

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Differences in the peripheral blood immune landscape between early-onset and late-onset colorectal cancer
(Frontiers Media, 2025-12-04) Sánchez-Menéndez, Clara; Rodríguez-Pérez, Jaime; Fuertes, Daniel; Leguizamon, Valentina; González-Sanmartín, María; Mateos, Elena; Cervero, Miguel; San José, Esther; Sanz, Gonzalo; Álvaro, Edurne; Ballestero-Pérez, Araceli; Martí-Gallostra, Marc; Rueda, José Antonio; Hurtado-Caballero, Elena; Pastor, Carlos; Balaguer, Francesc; Spinelli, Antonino; Martinez-Laso, Jorge; Torres, Montserrat; Perea, José; Coiras, Mayte; Spanish EOCRC Consortium (SECOC); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Ciencia e Innovación (España); Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Comisión Europea. NextGenerationEU; Comunidad de Madrid (España)
Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related mortality. While screening has reduced incidence in older adults, cases of early-onset CRC (EOCRC), diagnosed before age 50, are rising, highlighting the need to understand its unique biology. Immune responses, particularly T-cell infiltration measured by the tumor-based Immunoscore, are known predictors of CRC prognosis, but less is known about systemic immune differences by age at diagnosis. Methods: Peripheral blood mononuclear cells (PBMCs) from EOCRC (n=19) and late-onset CRC (LOCRC; n=19) participants recruited in Madrid (Spain) were analyzed for immune cell phenotypes, exhaustion markers, soluble cytokines, and metabolic activity. Results: Our study revealed distinct peripheral blood immune profiles differentiating EOCRC from LOCRC. EOCRC patients exhibited a heightened proinflammatory environment, with increased functional capacity of CD4+ Th1, Th9, and Th17 subsets to produce IFNg, IL-9, and IL-17A, respectively, and increased plasma levels of IFNg and CXCL8/IL-8. This suggests an active but potentially ineffective immune response. Conversely, LOCRC patients showed hallmarks of immunosenescence and chronic inflammation, including impaired cytokine production, higher frequencies of CD8+ Tgd and Th22 cells, and increased plasma CCL13/MCP-4, consistent with tissue remodeling and immune suppression. Biomarkers distinguishing EOCRC included reduced Th22 and CD8+ Tgd cell frequencies and higher NKT-like cells with increased IL-13 production by Th22 cells. Conclusions: EOCRC and LOCRC involved different immune mechanisms, where EOCRC showed an altered proinflammatory environment with preserved regulatory pathways, while LOCRC reflected age-related immune decline and inflammaging. Peripheral blood immune profiling offers a minimally invasive liquid Immunoscore for early detection and enables personalized immunotherapies for age-related immune landscapes, particularly benefiting younger individuals at risk of EOCRC.
Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration
(Elsevier, 2024-12-05) Apaza-Ticona, Luis; Beltran, Manuela; Moraga, Elisa; Cossio, David; Bermejo, Paulina; Guerra, José A; Alcamí, José; Bedoya, Luis M; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Ethnopharmacology relevance: Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases. Aim of the study: The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity. Material and methods: Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids. Results: n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription. Conclusions: n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.
ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma.
(Cell Press, 2025-01-08) Bachiller, Mireia; Barceló-Genestar, Nina; Rodriguez-Garcia, Alba; Alserawan, Leticia; Dobaño-López, Cèlia; Giménez-Alejandre, Marta; Castellsagué, Joan; Colell, Salut; Otero-Mateo, Marc; Antoñana-Vildosola, Asier; Español-Rego, Marta; Ferruz, Noelia; Pascal, Mariona; Martín-Antonio, Beatriz; Anguela, Xavier M; Fillat, Cristina; Olesti, Eulàlia; Calvo, Gonzalo; Juan, Manel; Delgado, Julio; Pérez-Galán, Patricia; Urbano-Ispizua, Álvaro; Guedan, Sonia; Fundación La Caixa; Ministerio de Ciencia e Innovación (España); Unión Europea. Comisión Europea. H2020; European Federation of Pharmaceutical Industries and Association; Asociación Española Contra el Cáncer; Agència de Gestió d´Ajuts Universitaris i de Recerca (AGAUR); Plan de Recuperación, Transformación y Resiliencia (España); Unión Europea. Comisión Europea. NextGenerationEU; Ministerio de Economía y Competitividad (España); Government of Catalonia (España); Instituto de Salud Carlos III; Consorci Institut D Investigacions Biomediques August Pi I Sunyer; Fundación Esther Koplowitz
CD19 CAR-T therapy has achieved remarkable responses in relapsed/refractory non-Hodgkin lymphoma (NHL). However, challenges persist, with refractory responses or relapses after CAR-T administration linked to CD19 loss or downregulation. Given the co-expression of CD19 and BCMA in NHL, we hypothesized that dual targeting could enhance long-term efficacy. We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, and loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. Comparison with anti-CD19/CD20 or anti-CD19/CD22 dual targeting was also performed. We demonstrate that anti-CD19/BCMA CAR-T cells can be effectively generated through the co-transduction of two lentiviral vectors after optimization to minimize competition for cellular resources. Co-transduced T cells, called ARI0003, effectively targeted NHL tumor cells with high avidity, outperforming anti-CD19 CAR-T cells and other dual-targeting approaches both in vitro and in vivo, particularly in low CD19 antigen density models. ARI0003 maintained effectiveness post-CD19 CAR-T treatment in xenograft models and in spheroids from relapsed CART-treated patients. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with a reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase 1 clinical trial (CARTD-BG-01; this study was registered at ClinicalTrials.gov [NCT06097455]) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.
Preclinical development of three novel CARs targeting CD79b for the treatment of non-Hodgkin's lymphoma and characterization of the loss of the target antigen
(BMJ Publishing Group, 2024-12-18) Esquinas, Esperanza; Moreno-Sanz, Alvaro; Sandá, Victor; Stodulski-Ciesla, Damian; Borregón, Jennifer; Peña-Blanque, Virginia; Fernández-Calles, Javier; Fernandez-Fuentes, Narcis; Serrano-Lopez, Juana; Juan, Manel; Engel, Pablo; Llamas-Sillero, Pilar; Solán-Blanco, Laura; Martín-Antonio, Beatriz; Instituto de Salud Carlos III; Ministerio de Sanidad (España); Comunidad de Madrid (España)
Background: Infusion of T cells modified with a chimeric antigen receptor (CAR) targeting CD19 has achieved exceptional responses in patients with non-Hodgkin's lymphoma (NHL), which led to the approval of CAR targeting CD19 (CART19) (Axi-cel and Liso-cel) as second line of treatment for adult patients with relapsed/refractory NHL. Unfortunately, 60% of patients still relapse after CART19 due to either a loss of expression of the target antigen (CD19) in the tumor cell, observed in 27% of relapsed patients, a limited CAR-T persistence, and additional mechanisms, including the suppression of the tumor microenvironment. Clinic strategies to prevent target antigen loss include sequential treatment with CARs directed at CD20 or CD22, which have caused loss of the second antigen, suggesting targeting other antigens less prone to disappear. CD79b, expressed in NHL, is a target in patients treated with antibody-drug conjugates (ADC). However, the limited efficacy of ADC suggests that a CAR therapy targeting CD79b might improve results. Methods: We designed three new CARs against CD79b termed CAR for Lymphoma (CARLY)1, 2 and 3. We compared their efficacy, phenotype, and inflammatory profiles with CART19 (ARI0001) and CARTBCMA (ARI0002h), which can treat NHL. We also analyzed the target antigen's expression loss (CD79b, CD19, and B-cell maturation antigen(BCMA)). Results: We found that CARLY2 and CARLY3 had high affinity and specificity towards CD79b on B cells. In vitro, all CAR-T cells had similar anti-NHL efficacy, which was retained in an NHL model of CD19- relapse. In vivo, CARLY3 showed the highest efficacy. Analysis of the loss of the target antigen demonstrated that CARLY cells induced CD79b and CD19 downregulation on NHL cells with concomitant trogocytosis of these antigens to T cells, being most notorious in CARLY2, which had the highest affinity towards CD79b and CD19, and supporting the selection of CARLY3 to design a new treatment for patients with NHL. Finally, we created a CAR treatment based on dual targeting of CD79b and BCMA to avoid losing the target antigen. This treatment showed the highest efficacy and did not cause loss of the target antigen. Conclusions: Based on specificity, efficacy, and loss of the target antigen, CARLY3 represents a potential novel CAR treatment for NHL.
Unintended HIV-1 Infection During Analytical Therapy Interruption
(Oxford University Press, 2020-04-27) Ugarte, Ainoa; Romero, Yolanda; Tricas, Amparo; Casado, Concepcion; Lopez-Galindez, Luis Cecilio; García, Felipe; Leal, Lorna; Ministerio de Economía (España); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); RETICS-Sida (RIS-ISCIII) (España); Government of Catalonia (España)
Differential microRNA expression profile between stimulated PBMCs from HIV-1 infected elite controllers and viremic progressors.
(Public Library of Science (PLOS), 2014) Egaña-Gorroño, Lander; Escribà, Tuixent; Boulanger, Nicolas; Guardo, Alberto Crespo; León, Agathe; Bargalló, Manel Enric; García, Felipe; Gatell, José María; Plana, Montserrat; Arnedo, Mireia; HIV Controllers Consortium of the AIDS Spanish Network; Lopez-Galindez, Luis Cecilio; Pernas, Maria; Casado, Concepcion; Alcamí, José; Government of Catalonia (España); Fundación para la Investigación y la Prevención del Sida en España; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Instituto de Salud Carlos III; RETICS-Sida (RIS-ISCIII) (España); Consorci Institut D Investigacions Biomediques August Pi I Sunyer
Background: The emerging relationship between microRNAs (miRNA) and viral-control is a topic of interest in the field of HIV. Host-genome might play an important role in the control of viremia. The aim of this study was to assess the specific miRNA profile that could contribute to the control of HIV replication in Elite Controllers. Results: After adequate normalization, expression profile of 286 human miRNAs (hsa-miR) was evaluated in phytohaemagglutinin-stimulated PBMCs from 29 individuals classified in 4 groups: 8 elite controllers (EC; viral load <50 cp/ml without treatment), 8 viremic progressors (VP; VL>5000 cp/ml without treatment), 8 patients under antiretroviral treatment (ART; VL<200 cp/ml) and 5 uninfected individuals (HIV-) through TaqMan Array Human microRNA Cards v3.0. A differential expression pattern consisting of 23 miRNAs became significantly different when comparing EC and VP. Profiling analysis segregated the population in two different blocks: while EC and HIV- clustered together in the same block (EC/HIV-_block 1), VP and ART individuals clustered together in a second block (VP/ART_block 2). Two inversely expressed miRNA patterns were determined within those two blocks: a set of 4 miRNAs (hsa-miR-221, -27a, -27b and -29b) was up-expressed in EC/HIV-_block and down-expressed in VP/ART_block while 19 miRNAs were down-expressed in block 1 and up-expressed in block 2. Differential miRNAs were successfully validated through individual RT-qPCR assays. Conclusions: Profile in EC resembled HIV- and differentially clusters with VP and ART. Therefore, differential clustering does not rely on undetectable viremia.
Olfactory Receptor OR2K2 Expression in Human Choroid Plexus as a Potential Marker in Early Sporadic Alzheimer's Disease
(Multidisciplinary Digital Publishing Institute (MDPI), 2024-03-21) Alves, Victoria Cunha; Figueiro-Silva, Joana; Trullas, Ramon; Ferrer, Isidre; Carro, Eva; Instituto de Salud Carlos III; Comunidad de Madrid (España); Centro de Investigación Biomédica en Red - CIBERNED (Enfermedades Neurodegenerativas)
Epithelial cells comprising the choroid plexus (CP) form a crucial barrier between the blood and the cerebrospinal fluid, thereby assuming a central position in brain homeostasis and signaling. Mounting evidence suggests that the impairment of CP function may be a significant contributor to Alzheimer's disease (AD) pathogenesis. CP function relies on the expression of specific receptors, and the potential involvement of olfactory receptors (ORs) and taste receptors (TASRs) in chemical surveillance within the CP is being investigated. Previous studies have implicated ORs and TASRs in neurodegenerative disorders like AD, although the direct evidence of their expression in the human CP remains to be established. In this study, we conducted a transcriptomic analysis encompassing eleven and in the CP, comparing samples from healthy age-matched controls to those from patients with AD spanning Braak stages I to VI. Among these receptors, a striking finding emerged- exhibited robust expression, with a statistically significant upregulation noted at Braak stage I. Surprisingly, at the protein level, OR2K2 showed a significant decrease in both Braak stage I and VI. Additionally, we identified CP epithelial cells as the source of OR2K2 expression, where it colocalized with autophagy markers LC3 and p62. We postulate that OR2K2 could be subjected to degradation by autophagy in the early stages of AD, triggering a compensatory mechanism that leads to increased mRNA transcription. This study uncovers a potential role for OR2K2 in AD pathogenesis, offering a novel perspective on the intricate dynamics at play in this neurodegenerative disorder.
Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients
(Wiley, 2022-02) Martin-Vicente, Maria; Almansa, Raquel; Martinez, Isidoro; Tedim, Ana P; Bustamante, Elena; Tamayo, Luis; Aldecoa, César; Gómez, José Manuel; Renedo, Gloria; Berezo, Jose Ángel; Cedeño, Jamil Antonio; Mamolar, Nuria; García Olivares, Pablo; Herrán-Monge, Rubén; Cicuendez, Ramón; Enríquez, Pedro; Ortega, Alicia; Jorge, Noelia; Doncel, Cristina; de la Fuente, Amanda; Bustamante-Munguira, Juan; Muñoz-Gómez, María José; González-Rivera, Milagros; Puertas, Carolina; Mas-Lloret, Vicente; Vazquez-Alcaraz, Monica; Perez-Garcia, Felipe; Rico-Feijoo, Jesús; Martín, Silvia; Motos, Anna; Fernandez-Barat, Laia; Eiros, José María; Domínguez-Gil, Marta; Ferrer, Ricard; Barbé, Ferrán; Trapiello, Wysali; Kelvin, David J; Bermejo-Martin, Jesús F; Resino, Salvador; Torres, Antoni; Canadian Institutes of Health Research; Nova Scotia Health Research Foundation; Atlantic Genome (Canada); Li Ka Shing Foundation; Dalhousie Medical Research Foundation; Canada Research Chairs; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERES (Enfermedades Respiratorias); Junta de Castilla y León (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Background: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. Patients/methods: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. Results: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). Conclusions: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.
Cross-sectional and longitudinal associations of adherence to WCRF/AICR cancer prevention recommendations with health-related quality of life in breast cancer survivors. Health-EpiGEICAM study
(Elsevier, 2024-08) Lope Carvajal, Virginia; Guerrero-Zotano, Ángel; Fernandez de Larrea-Baz, Nerea; Antolín, Silvia; Benavent Viñuales, Marta; Bermejo, Begoña; Ruiz Moreno, Emma; Baena-Cañada, José Manuel; París, Lorena; Antón, Antonio; Chacón, José Ignacio; Muñoz, Montserrat; García-Sáenz, José Ángel; Olier, Clara; Sánchez Rovira, Pedro; Arcusa Lanza, Angels; González, Sonia; Brunet, Joan; Oltra, Amparo; Bezares, Susana; Rosell, Libertad; Perez-Gomez, Beatriz; Pastor-Barriuso, Roberto; Martín, Miguel; Pollan-Santamaria, Marina; Asociación Española Contra el Cáncer; Instituto de Salud Carlos III
Objectives: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later. Design: Prospective cohort study. Settings and participants: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals. Measurements: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores. Results: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time. Conclusions: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors.
Targeted Next-Generation Sequencing in a Large Cohort of Genetically Undiagnosed Patients with Neuromuscular Disorders in Spain.
(2020-05-11) Gonzalez-Quereda, Lidia; Rodriguez, Maria Jose; Diaz-Manera, Jordi; Alonso-Perez, Jorge; Gallardo, Eduard; Nascimento, Andres; Ortez, Carlos; Natera-de Benito, Daniel; Olive, Montse; Gonzalez-Mera, Laura; Munain, Adolfo Lopez de; Zulaica, Miren; Poza, Juan Jose; Jerico, Ivonne; Torne, Laura; Riera, Pau; Milisenda, Jose; Sanchez, Aurora; Garrabou, Gloria; Llano, Isabel; Madruga-Garrido, Marcos; Gallano, Pia
The term neuromuscular disorder (NMD) includes many genetic and acquired diseases and differential diagnosis can be challenging. Next-generation sequencing (NGS) is especially useful in this setting given the large number of possible candidate genes, the clinical, pathological, and genetic heterogeneity, the absence of an established genotype-phenotype correlation, and the exceptionally large size of some causative genes such as TTN, NEB and RYR1. We evaluated the diagnostic value of a custom targeted next-generation sequencing gene panel to study the mutational spectrum of a subset of NMD patients in Spain. In an NMD cohort of 207 patients with congenital myopathies, distal myopathies, congenital and adult-onset muscular dystrophies, and congenital myasthenic syndromes, we detected causative mutations in 102 patients (49.3%), involving 42 NMD-related genes. The most common causative genes, TTN and RYR1, accounted for almost 30% of cases. Thirty-two of the 207 patients (15.4%) carried variants of uncertain significance or had an unidentified second mutation to explain the genetic cause of the disease. In the remaining 73 patients (35.3%), no candidate variant was identified. In combination with patients' clinical and myopathological data, the custom gene panel designed in our lab proved to be a powerful tool to diagnose patients with myopathies, muscular dystrophies and congenital myasthenic syndromes. Targeted NGS approaches enable a rapid and cost-effective analysis of NMD- related genes, offering reliable results in a short time and relegating invasive techniques to a second tier.
Microbial Phenolic Metabolites Are Associated with Improved Cognitive Health
(Wiley, 2024-01) Domínguez-López, Inés; Galkina, Polina; Parilli-Moser, Isabella; Arancibia-Riveros, Camila; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Malcampo, Mireia; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Bueno-Cavanillas, Aurora; Tur, Josep A; Rubín-García, María; Pintó, Xavier; Fernández-Aranda, Fernando; Delgado-Rodríguez, Miguel; Barabash-Bustelo, Ana; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Toledo, Estefanía; Atzeni, Alessandro; Asensio, Eva M; Vera, Natàlia; Garcia-Rios, Antonio; Torres-Collado, Laura; Pérez-Farinós, Napoleón; Zulet, Marian; Chaplin, Alice; Casas, Rosa; Martín-Peláez, Sandra; Vaquero-Luna, Jessica; Gómez-Pérez, Ana Maria; Vazquez-Ruiz, Zenaida; Shyam, Sangeetha; Ortega-Azorín, Carolina; Talens, Natàlia; Peña-Orihuela, Patricia J; Oncina-Canovas, Alejandro; Diez-Espino, Javier; Babio, Nancy; Fitó, Montserrat; Lamuela-Raventós, Rosa M
Scope: Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk. Methods and results: A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores. Conclusions: These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.
Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population
(Springer, 2024-01-13) Baenas, I; Camacho-Barcia, L; Granero, R; Razquin, C; Corella, D; Gómez-Martínez, Carlos; Castañer-Niño, O; Martínez, JA; Alonso-Gómez, ÁM; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, J; Estruch, R; Tinahones, Francisco J; Lapetra, J; Serra-Majem, Lluis; Cano-Ibáñez, N; Tur, Josep A; Martín-Sánchez, V; Pintó, X; Gaforio, J J; Matía-Martín, P; Vidal, Josep; Vazquez, Clotilde; Daimiel, L; Ros, Emilio; Jiménez-Murcia, S; Dalsgaard, S; Garcia-Arellano, A; Babio, N; Sorli, Jose V; Lassale, C; García-de-la-Hera, M; Gómez-García, E; Zulet, MA; Konieczna, Jadwiga; Martín-Peláez, S; Tojal-Sierra, Lucas; Basterra-Gortari, FJ; de Las Heras-Delgado, S; Portoles, O; Muñoz-Pérez, MÁ; Arenas-Larriva, AP; Compañ-Gabucio, L; Eguaras, S; Shyam, Sangeetha; Fitó, M; Baños, RM; Salas-Salvado, Jordi; Fernández-Aranda, F
Objectives: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. Methods: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. Results: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. Conclusions: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.
Role of PATJ in stroke prognosis by modulating endothelial to mesenchymal transition through the Hippo/Notch/PI3K axis
(Nature Publishing Group, 2024-02-17) Medina-Dols, Aina; Cañellas, Guillem; Capó, Toni; Solé, Montse; Mola-Caminal, Marina; Cullell, Natalia; Jaume, Marina; Nadal-Salas, Laura; Llinàs, Jaume; Gómez, Lluis; Tur Campos, Silvia; Jiménez Martínez, Carmen; Diaz Navarro, Rosa; Carrera, Caty; Muiño, Elena; Gallego-Fabrega, Cristina; Soriano-Tarraga, Carolina; Ruiz-Guerra, Laura; Pol-Fuster, Josep; Asensio, Víctor José; Muncunill Farreny, Josep; Fleischer, Aarne; Iglesias, Amanda; Giralt-Steinhauer, Eva; Lazcano, Uxue; Fernández-Pérez, Isabel; Jiménez-Balado, Joan; Gabriel-Salazar, Marina; Garcia-Gabilondo, Miguel; Lei, Ting; Torres-Aguila, Nuria-Paz; Cárcel-Márquez, Jara; Lladó, Jerònia; Olmos, Gabriel; Rosell, Anna; Montaner, Joan; Planas, Anna M; Rabionet, Raquel; Hernández-Guillamon, Mar; Jiménez-Conde, Jordi; Fernández-Cadenas, Israel; Vives-Bauza, Cristofol
Through GWAS studies we identified PATJ associated with functional outcome after ischemic stroke (IS). The aim of this study was to determine PATJ role in brain endothelial cells (ECs) in the context of stroke outcome. PATJ expression analyses in patient's blood revealed that: (i) the risk allele of rs76221407 induces higher expression of PATJ, (ii) PATJ is downregulated 24 h after IS, and (iii) its expression is significantly lower in those patients with functional independence, measured at 3 months with the modified Rankin scale ((mRS) ≤2), compared to those patients with marked disability (mRS = 4-5). In mice brains, PATJ was also downregulated in the injured hemisphere at 48 h after ischemia. Oxygen-glucose deprivation and hypoxia-dependent of Hypoxia Inducible Factor-1α also caused PATJ depletion in ECs. To study the effects of PATJ downregulation, we generated PATJ-knockdown human microvascular ECs. Their transcriptomic profile evidenced a complex cell reprogramming involving Notch, TGF-ß, PI3K/Akt, and Hippo signaling that translates in morphological and functional changes compatible with endothelial to mesenchymal transition (EndMT). PATJ depletion caused loss of cell-cell adhesion, upregulation of metalloproteases, actin cytoskeleton remodeling, cytoplasmic accumulation of the signal transducer C-terminal transmembrane Mucin 1 (MUC1-C) and downregulation of Notch and Hippo signaling. The EndMT phenotype of PATJ-depleted cells was associated with the nuclear recruitment of MUC1-C, YAP/TAZ, β-catenin, and ZEB1. Our results suggest that PATJ downregulation 24 h after IS promotes EndMT, an initial step prior to secondary activation of a pro-angiogenic program. This effect is associated with functional independence suggesting that activation of EndMT shortly after stroke onset is beneficial for stroke recovery.
Increased grey matter volumes in the temporal lobe and its relationship with cognitive functioning in euthymic patients with bipolar disorder.
(Elsevier, 2024-02-15) Porta-Casteràs, D; Vicent-Gil, M; Serra-Blasco, M; Navarra-Ventura, Guillem; Solé, B; Montejo, L; Torrent, C; Martinez-Aran, A; De la Peña-Arteaga, V; Palao, D; Vieta, E; Cardoner, N; Cano, M
Background: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear. Methods: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains. Results: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008). Limitations: We evaluated a modest sample size with concurrent pharmacological treatment. Conclusions: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management.
Yearly attained adherence to Mediterranean diet and incidence of diabetes in a large randomized trial
(BioMed Central (BMC), 2023-09-29) Martínez-González, Miguel A; Montero, Pedro; Ruiz-Canela, Miguel; Toledo, Estefanía; Estruch, Ramón; Gómez-Gracia, Enrique; Li, Jun; Ros, Emilio; Arós, Fernando; Hernáez, Alvaro; Corella, Dolores; Fiol Sala, Miquel; Lapetra, José; Serra-Majem, Lluis; Pintó, Xavier; Cofán, Montse; Sorli, Jose V; Babio, Nancy; Márquez-Sandoval, Yolanda F; Castañer, Olga; Salas-Salvado, Jordi
Background: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet. Methods: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes. Results: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results. Conclusions: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.
Ultra-processed foods consumption as a promoting factor of greenhouse gas emissions, water, energy, and land use: A longitudinal assessment
(Elsevier, 2023-05-24) Garcia, Silvia; Pastor, Rosario; Monserrat-Mesquida, Margalida; Álvarez-Álvarez, Laura; Rubín-García, María; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Fito, Montserrat; Martínez, J Alfredo; Tojal-Sierra, Lucas; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; López-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Santos-Lozano, José Manuel; Serra-Majem, Lluis; Cano-Ibañez, Naomi; Pintó, Xavier; Delgado-Rodriguez, Miguel; Matía-Martín, Pilar; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Buil-Cosiales, Pilar; Martínez-Rodríguez, María Ángeles; Coltell, Oscar; Castañer, Olga; Garcia-Rios, Antonio; Barceló Cañellas, María de la Concepión; Gómez-Gracia, Enrique; Zulet, Maria Ángeles; Konieczna, Jadwiga; Casas, Rosa; Massó-Guijarro, Paloma; Goicolea-Güemez, Leire; Rosa Bernal-Lopez, Maria; Bes-Rastrollo, Maira; Shyam, Sangeetha; González, José I; Zomeño-Fajardo, María Dolores; Peña-Orihuela, Patricia J; González-Palacios, Sandra; Toledo, Estefanía; Khoury, Nadine; Perez, Karla Alejandra; Martín-Sánchez, Vicente; Tur, Josep A; Bouzas, Cristina
Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability. Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use. Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome. Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models. Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO2eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced. Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection. Trial registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870.
Sex differences in the comorbidity of patients seeking a first treatment for Alcohol Use Disorder
(Springer, 2023) García-Marchena, Nuria; Sanvisens, Arantza; Abellí-Deulofeu, Enric; Blanes, Rafael; Torrens, Marta; Miquel, Laia; Rubio, Gabriel; Bolao, Ferran; Muga, Robert; Zuluaga, Paola; Fuster, Daniel; Hernández-Rubio, Anna; Farre, Magi; Papasseit, Esther; Pérez-Mañá, Clara; Poyatos, Lourdes; Moranta, Catalina; Sion, Ana; Ortega, Lluisa; Bruguera, Pol; Caballeria, Elsa; Messeguer, Ana; Fonseca, Francina; Mestre-Pinto, Joan-Ignasi; Alías, María; Dinamarca, Fernando; Rodríguez-Fonseca, Fernando; Pavón-Morón, Francisco Javier; Marcos, Miguel; Martín, Candelaria; Pérez-Hernández, Onán; Manzanares, Jorge; Navarrete, Francisco; Gasparyan, Ani
Background: The CohRTA multicenter study aims to characterize patients undergoing a first treatment for alcohol use disorder (AUD). The objective is to analyze sex-specific differences in the comorbidity of AUD when starting the first treatment for the disorder. Methods: A multicenter study was carried out between 2014 and 2021 in 6 public centers in Spain. Sociodemographic characteristics were collected, variables related to alcohol consumption, medical comorbidity according to Cumulative Illness Rating Scale-Substance Abuse (CIRS-SA), antecedent of psychiatric comorbidity, general blood test and screening for drugs in urine. Logistic regression models were used to establish associations. Results: A total of 896 patients (634 M, 262 W) were included. Median age at admission was 48 years [IQR:41ﾖ56 years]. Men reported beginning regular alcohol consumption at an earlier age and drank more alcohol. The most frequent medical comorbidities were hepatic, respiratory, vascular and neurological. The median number of affected systems was three, with no differences between men and women. However, depressive disorder was more frequent in women. In the multivariate analysis, women were up to 4 times more likely to have a major depressive disorder, elevated ESR and elevated total cholesterol than men. Men started alcohol consumption earlier, had a higher body mass index (BMI), a higher probability of using cocaine and a higher frequency of GGT and bilirubin alteration than women. Conclusion: Differences by sex were found among individuals beginning first treatment for AUD. These differences must be taken into account when designing specific therapeutic strategies for men and women.
Plasma metabolite profiles associated with the World Cancer Research Fund/American Institute for Cancer Research lifestyle score and future risk of cardiovascular disease and type 2 diabetes
(BioMed Central (BMC), 2023-09-16) Rios, Santiago; García-Gavilán, Jesús F; Babio, Nancy; Paz-Graniel, Indira; Ruiz-Canela, Miguel; Liang, Liming; Clish, Clary B; Toledo, Estefanía; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol Sala, Miquel; Guasch-Ferré, Marta; Santos-Lozano, José Manuel; Li, Jun; Razquin, Cristina; Martínez-González, Miguel Ángel; Hu, Frank B; Salas-Salvado, Jordi
Background: A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk. Methods: In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models. Results: The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained or attenuated, respectively, for the 1-year metabolomic profile. Conclusions: In an elderly population at high risk of CVD, a set of metabolites was selected as potential metabolites associated with the HL pattern predicting the risk of T2D and, to a lesser extent, CVD. These results support previous findings that some of these metabolites are inversely associated with the risk of T2D and CVD. Trial registration: The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/ , ISRCTN35739639).
Olive oil consumption, plasma metabolites, and risk of type 2 diabetes and cardiovascular disease
(BioMed Central (BMC), 2023-12-13) García-Gavilán, Jesús F; Babio, Nancy; Toledo, Estefanía; Semnani-Azad, Zhila; Razquin, Cristina; Dennis, Courtney; Deik, Amy; Corella, Dolores; Estruch, Ramón; Ros, Emilio; Fitó, Montserrat; Arós, Fernando; Fiol Sala, Miquel; Lapetra, José; Lamuela-Raventos, Rosa; Clish, Clary; Ruiz-Canela, Miguel; Martínez-González, Miguel Ángel; Hu, Frank; Salas-Salvado, Jordi; Guasch-Ferré, Marta
Background: Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD. Methods: The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models. Results: We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and the multi-metabolite profile were 0.40 (95% CI 0.37, 0.44) and 0.27 (95% CI 0.22, 0.31) for the discovery and validation sample, respectively. We identified several overlapping and distinct metabolites according to the type of olive oil consumed. The baseline metabolite profiles of total and extra virgin olive oil were inversely associated with CVD incidence (HR per 1SD: 0.79; 95% CI 0.67, 0.92 for total olive oil and 0.70; 0.59, 0.83 for extra virgin olive oil) after adjustment for confounders. However, no significant associations were observed between these metabolite profiles and T2D incidence. Conclusions: This study reveals a panel of plasma metabolites linked to the consumption of total and specific types of olive oil. The metabolite profiles of total olive oil consumption and extra virgin olive oil were associated with a decreased risk of incident CVD in a high cardiovascular-risk Mediterranean population, though no associations were observed with T2D incidence. Trial registration: The PREDIMED trial was registered at ISRCTN (http://www.isrctn.com/ , ISRCTN35739639).
Metabolic syndrome criteria and severity and carbon dioxide (CO2) emissions in an adult population
(BioMed Central (BMC), 2023-07-13) Garcia, Silvia; Pastor, Rosario; Monserrat-Mesquida, Margalida; Álvarez-Álvarez, Laura; Rubín-García, María; Martínez-González, Miguel Ángel; Salas-Salvado, Jordi; Corella, Dolores; Goday, Albert; Martínez, J Alfredo; Alonso-Gómez, Ángel M; Wärnberg, Julia; Vioque, Jesus; Romaguera, Dora; Lopez-Miranda, José; Estruch, Ramon; Tinahones, Francisco J; Lapetra, José; Serra-Majem, Lluis; Riquelme-Gallego, Blanca; Pintó, Xavier; Gaforio, José J; Matía, Pilar; Vidal, Josep; Vazquez, Clotilde; Daimiel, Lidia; Ros, Emilio; Sayon-Orea, Carmen; Guillem-Saiz, Patricia; Valle-Hita, Cristina; Cabanes, Robert; Abete, Itziar; Goicolea-Güemez, Leire; Gómez-Gracia, Enrique; Tercero-Maciá, Cristina; Colom Fernández, Antoni; García-Ríos, Antonio; Castro-Barquero, Sara; Fernández-García, José Carlos; Santos-Lozano, José Manuel; Cenoz, Juan Carlos; Barragán, Rocío; Khoury, Nadine; Castañer, Olga; Zulet, María Ángeles; Vaquero-Luna, Jessica; Bes-Rastrollo, Maira; de Las Heras-Delgado, Sara; Ciurana, Ramon; Martín-Sánchez, Vicente; Tur, Josep A; Bouzas, Cristina
Background: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet. Aims: To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population. Design: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS). Methods: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score. Results: Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions. Conclusions: Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet. Trial registration: ISRCTN, ISRCTN89898870 . Registered 05 September 2013.

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