Examinando por Autor "Baldán-Martín, Montse"

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Characterization of the Regulatory Landscape in Crohn’s Disease Reveals microRNA-Associated Alterations that Shape Anti-TNF Response
(Oxford, 2025-03-11) Cervera-Seco, Luis; Baldán-Martín, Montse; Fernández-Tomé, Samuel; Ortega Moreno, Lorena; Lozano, Juan J.; Aransay, Ana M.; Chaparro , María; Gisbert, Javier P.; Marigorta, Urko M.
Background: MicroRNAs (miRNAs) play a key role in regulating gene expression in Crohn’s disease (CD). Although several studies have identified miRNAs with biomarker potential, an exhaustive characterization of the miRNAome in CD is still lacking. We performed the largest miRNA prof iling effort to date to analyze miRNA variability across intestinal tissues, disease activity status, and infliximab treatment in CD. Methods: We generated 119 transcriptomic profiles from the terminal ileum and left colon biopsies of 30 individuals (10 with active CD, 10 with quiescent CD, and 10 healthy controls). Half of the samples were cultured ex vivo with infliximab, and the remaining half with basal medium. Using variance analyses and linear mixed differential expression models, we explored the determinants of miRNAome variability in CD. We also generated infliximab response signatures to identify candidates and examine interactions between miRNAs and the coding transcriptome. Results: Tissue location, and patient-specific effects, were the main factors in miRNA variability in CD, with some differentially expressed miRNAs involved in epithelial–mesenchymal transition (miR-200s, miR-429). We identified 9 miRNAs with treatment-responsive behaviour, particularly to the terminal ileum of active CD cases. Although the changes observed in active CD cases suggest that many alterations are not offset by infliximab incubation, we described 13 miRNAs–mRNA pairs with potential involvement in the anti-tumor necrosis factor (TNF) treatment, 7 of which have been already validated. Conclusions: A comprehensive miRNA profiling revealed significant intestinal tissue-specific variability and identified key alterations in the miRNA–mRNA interactome that might be involved in therapeutic response to anti-TNF in CD.
Lunasin Peptide is a Modulator of the Immune Response in the Human Gastrointestinal Tract
(Wiley, 2021-04-22) Fernández-Tomé, Samuel; Indiano-Romacho, Pedro; Mora-Gutiérrez, Irene; Pérez-Rodríguez, Leticia; Ortega Moreno, Lorena; Marin, Alicia C; Baldán-Martín, Montse; Moreno-Monteagudo, Jose Andrés; Santander, Cecilio; Chaparro, María; Hernández-Ledesma, Blanca; Gisbert P., Javier; Bernardo, David
Introduction: Lunasin is a soybean bioactive peptide with a variety of beneficial properties against chronic disorders. However, its effect in human primary intestinal cells remains unknown. Hence, this study aims to characterize its ex vivo biological activity in the human intestinal mucosa. Methods and Results: Human intestinal biopsies, obtained from healthy controls, are ex vivo conditioned with lunasin both in the presence/absence of lipopolysaccharide (LPS). Peptide maintains its stability during biopsy culture by HPLC-MS/MS analysis. Lunasin is bioactive in the human mucosa, as it induces IL-1𝜷, TNF-𝜶, IL-17A, CCL2, and PGE2/COX-2 gene expression together with an increased expression of tolerogenic IL-10 and TGF𝜷, while it also downregulates the expression of iNOS and subunit p65 from NF-𝜿B. Indeed, lunasin also abrogates the LPS-induced pro-inflammatory response, downregulating IL-17A, IFN𝜸, and IL-8 expression, and inducing IL-10 and TGF𝜷 expression. These results are also mirrored in the cell-free culture supernatants at the protein level by Multiplex. Moreover, lunasin further induces a regulatory phenotype and function on human intestinal conventional dendritic cell and macrophage subsets as assessed by flow cytometry. Conclusions: We hereby have characterized lunasin as an immunomodulatory peptide with potential capacity to prevent immune and inflammatory-mediated disorders in the human gastrointestinal tract.
Proteomic Profiling of Extracellular Vesicles in Inflammatory Bowel Diseases
(MDPI, 2025-01-09) Baldán-Martín, Montse; Azkargorta , Mikel; Lapitz, Ainhoa; Ortega Moreno, Lorena; Iloro, Ibon; Fernández-Tomé, Samuel; Arbelaiz, Ander; Escobes, Iraide; Marín, Alicia C.; Bernardo, David; Bujanda, Luis; Bañales, Jesús M.; Elortza, Félix; Gisbert, Javier P.; Chaparro, María
Background: The proteomic analysis of serum extracellular vesicles (EVs) could be a useful tool for studying the pathophysiology of Crohn’s disease (CD) and ulcerative colitis (UC), as well as for biomarker discovery. Aims: To characterize the proteomic composition of serum EVs in patients with CD and UC to identify biomarkers and molecular pathways associated with pathogenesis and activity. Methods: Serum EVs were enriched and analyzed in patients with quiescent CD, active CD (aCD), quiescent UC, active UC (aUC), and healthy controls (HCs) (n = 30 per group). All groups were matched for age and sex. Disease activity was assessed by ileocolonoscopy and categorized based on the SES-CD (CD) and the endoscopic sub-score of the Mayo Score (UC). EVs were enriched by ultracentrifugation, and their size and concentration were determined by nanoparticle tracking analysis. The expression of CD63, CD81, and CD9 was determined using Western blotting. Proteomic analysis was performed by label-free nano-LC MS/MS. Results: A total of 324 proteins were identified; 60 showed differential abundance in CD-HC, 34 in UCHC, and 21 in CD-UC. Regarding disease activity, the abundance of 58 and 32 proteins was altered in aCD-HC and aUC-HC, respectively. Functional analyses revealed that proteins associated with aCD were involved in immune regulation, whereas those linked to aUC were enriched in oxidative stress. Conclusions: We have identified expressed proteins between EVs from patients with CD and UC, depending on the presence of disease, the disease type, and the disease activity. These proteins are potential candidates as disease biomarkers and open new research avenues to better understand these conditions.