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1. P026 Differential effects of tofacitinib on macrophage activation may contribute to lack of response in ulcerative colitis patients

Author

Melón-Ardanaz, E, primary, Veny, M, additional, Corraliza, A M, additional, Garrido-Trigo, A, additional, Gudiño, V, additional, Moro, M, additional, Sanzo-Machuca, Á, additional, Esteller, M, additional, Masamunt, M C, additional, Caballol, B, additional, Ordás, I, additional, Fernández-Clotet, A, additional, Ricart, E, additional, Panés, J, additional, and Salas, A, additional

Published
2024
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2. DOP45 Blood-derived neutrophils give rise to differentially activated populations in the mucosa of active Inflammatory Bowel Disease patients

Author

Veny, M, primary, Sanzo-Machuca, A, additional, Corraliza, A M, additional, Strobbe, F, additional, Garrido-Trigo, A, additional, Gudiño, V, additional, Melón-Ardanaz, E, additional, Esteller, M, additional, Teubel, I, additional, Masamunt, M C, additional, Ordás, I, additional, Prieto, C, additional, Giner, À, additional, Martin-Cardona, A, additional, Esteve, M, additional, Ricart, E, additional, and Salas, A, additional

Published
2024
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4. DOP05 Single-cell RNAseq temporal analysis of ulcerative colitis patients undergoing tofacitinib treatment reveals a shift in myeloid cells towards pro-inflammatory phenotypes in refractory patients

Author

Melón-Ardanaz, E, primary, Veny, M, additional, Corraliza, A M, additional, Garrido-Trigo, A, additional, Esteller, M, additional, Rodrigo, M, additional, Verstockt, B, additional, Vermeire, S, additional, Masamunt, M C, additional, Giner, Á, additional, Ordás, I, additional, Fernández-Clotet, A, additional, Ricart, E, additional, Panés, J, additional, and Salas, A, additional

Published
2023
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6. Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome: Jejunal Barrier Alterations Underlying Clinical Manifestations

Author

Cristina Pardo-Camacho, John-Peter Ganda Mall, Cristina Martínez, Marc Pigrau, Elba Expósito, Mercé Albert-Bayo, Elisa Melón-Ardanaz, Adoración Nieto, Bruno Rodiño-Janeiro, Marina Fortea, Danila Guagnozzi, Amanda Rodriguez-Urrutia, Inés de Torres, Ignacio Santos-Briones, Fernando Azpiroz, Beatriz Lobo, Carmen Alonso-Cotoner, Javier Santos, Ana M. González-Castro, Maria Vicario, Institut Català de la Salut, [Pardo-Camacho C] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Ganda Mall JP] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. [Martínez C] Vascular and Renal Translational Research Group, Lleida Institute for Biomedical Research Dr. Pifarré. Foundation (IRBLleida), Lleida, Spain. [Pigrau M] Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Expósito E, González-Castro AM] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Albert-Bayo M, Melón-Ardanaz E, Fortea M] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Nieto A] Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Gastroenterologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rodiño-Janeiro B] Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Guagnozzi D] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Gastroenterologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rodriguez-Urrutia A] Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Salut Mental, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain. [Torres I] Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Santos-Briones I] Facultat Ciències de la Salut, Universitat Ramon LLull-Blanquerna, Barcelona, Spain. [Azpiroz F] Servei de Gastroenterologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. [Lobo B] Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Gastroenterologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Alonso-Cotoner C, Santos J] Laboratori de Neuroimmuno-Gastroenterologia, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei de Gastroenterologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain. [Vicario M] Laboratori d’Immunologia Translacional, Unitat de Recerca d’Aparell Digestiu, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Department of Gastrointestinal Health, Nestlé Institute of Health Sciences, Société des Produits Nestlé S.A., Nestlé Research, Vers-chez-les-Blanc, Lausanne, Switzerland, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Diarrhea, Còlon irritable - Complicacions, Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Digestive::Diarrhea [DISEASES], afecciones patológicas, signos y síntomas::signos y síntomas::signos y síntomas digestivos::diarrea [ENFERMEDADES], enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedades del colon::enfermedades funcionales del colon::síndrome del colon irritable [ENFERMEDADES], Plasma Cells, intestinal plasma cells, intestinal glycocalyx, IBS-D, mucosal ultrastructure, intestinal barrier dysfunction, mucosal nerve fibres, General Medicine, Glycocalyx, Irritable Bowel Syndrome, Hemic and Immune Systems::Hemic and Immune Systems::Immune System::Antibody-Producing Cells::B-Lymphocytes::Hemic and Immune Systems::Immune System::Plasma Cells [ANATOMY], Nerve Fibers, Other Clinical Medicine, sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::sistema inmunológico::células productoras de anticuerpos::linfocitos B::sistemas sanguíneo e inmunológico::sistema inmunológico::células plasmáticas [ANATOMÍA], Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Colonic Diseases::Colonic Diseases, Functional::Irritable Bowel Syndrome [DISEASES], Annan klinisk medicin, Humans, Intestinal Mucosa, Diarrea, Leucòcits - Metabolisme
Abstract

Intestinal barrier dysfunction; Intestinal glycocalyx; Mucosal nerve fibres Disfunción de la barrera intestinal; Glicocálix intestinal; Fibras nerviosas de la mucosa Disfunció de la barrera intestinal; Glicocàlix intestinal; Fibres nervioses de la mucosa Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology. This study was funded in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP18/00116 (C.M.), PI19/01643 (B.L.); PI17/01443 (D.G.); PI15/00301 (C.A.-C.), PI17/0190 (J.S.), PI19/01643 & CPII16/00031, (M.V.); CIBEREHD CB06/04/0021 (F.A., C.A.-C., J.S., M.V.); Ministerio de Educación, Dirección General de Investigación: SAF 2016-76648-R (F.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca, de la Generalitat de Catalunya: 2014 SGR 1285 (F.A.); Vall d’Hebron Institut de Recerca, Programa de becas predoctorales Amics de Vall d’Hebron: PRED-VHIR-2016-34 (C.P.-C.), PRED-VHIR-2014-018 (M.F.), the Swedish Research Council dnr 2019-00653 (J.-P.G.M.), and the European Union’s Horizon research and innovation programme 2020, grant no. 848228 (E.E., A.R.-U., B.L., C.A.-C., J.S.).

Published
2022
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7. Single-cell integration reveals metaplasia in inflammatory gut diseases.

Author

Oliver AJ, Huang N, Bartolome-Casado R, Li R, Koplev S, Nilsen HR, Moy M, Cakir B, Polanski K, Gudiño V, Melón-Ardanaz E, Sumanaweera D, Dimitrov D, Milchsack LM, FitzPatrick MEB, Provine NM, Boccacino JM, Dann E, Predeus AV, To K, Prete M, Chapman JA, Masi AC, Stephenson E, Engelbert J, Lobentanzer S, Perera S, Richardson L, Kapuge R, Wilbrey-Clark A, Semprich CI, Ellams S, Tudor C, Joseph P, Garrido-Trigo A, Corraliza AM, Oliver TRW, Hook CE, James KR, Mahbubani KT, Saeb-Parsy K, Zilbauer M, Saez-Rodriguez J, Høivik ML, Bækkevold ES, Stewart CJ, Berrington JE, Meyer KB, Klenerman P, Salas A, Haniffa M, Jahnsen FL, Elmentaite R, and Teichmann SA

Subjects
Adult, Humans, Brunner Glands metabolism, Case-Control Studies, Celiac Disease pathology, Colitis, Ulcerative pathology, Crohn Disease pathology, Crohn Disease immunology, Datasets as Topic, Gastric Mucosa immunology, Gastric Mucosa pathology, Gastrointestinal Neoplasms immunology, Gastrointestinal Neoplasms pathology, Gastrointestinal Tract immunology, Gastrointestinal Tract pathology, Health, Intestinal Mucosa immunology, Intestinal Mucosa pathology, Neutrophils immunology, Pylorus metabolism, Quality Control, Single-Cell Gene Expression Analysis, Stem Cells immunology, Stem Cells metabolism, Stem Cells pathology, T-Lymphocytes immunology, Child, Epithelial Cells pathology, Gastrointestinal Diseases pathology, Gastrointestinal Diseases immunology, Inflammation pathology, Inflammation immunology, Metaplasia pathology, Single-Cell Analysis methods
Abstract

The gastrointestinal tract is a multi-organ system crucial for efficient nutrient uptake and barrier immunity. Advances in genomics and a surge in gastrointestinal diseases 1,2 has fuelled efforts to catalogue cells constituting gastrointestinal tissues in health and disease 3 . Here we present systematic integration of 25 single-cell RNA sequencing datasets spanning the entire healthy gastrointestinal tract in development and in adulthood. We uniformly processed 385 samples from 189 healthy controls using a newly developed automated quality control approach (scAutoQC), leading to a healthy reference atlas with approximately 1.1 million cells and 136 fine-grained cell states. We anchor 12 gastrointestinal disease datasets spanning gastrointestinal cancers, coeliac disease, ulcerative colitis and Crohn's disease to this reference. Utilizing this 1.6 million cell resource (gutcellatlas.org), we discover epithelial cell metaplasia originating from stem cells in intestinal inflammatory diseases with transcriptional similarity to cells found in pyloric and Brunner's glands. Although previously linked to mucosal healing 4 , we now implicate pyloric gland metaplastic cells in inflammation through recruitment of immune cells including T cells and neutrophils. Overall, we describe inflammation-induced changes in stem cells that alter mucosal tissue architecture and promote further inflammation, a concept applicable to other tissues and diseases., Competing Interests: Competing interests: S.A.T. is a scientific advisory board member of ForeSite Labs, OMass Therapeutics, a co-founder and equity holder of TransitionBio and EnsoCell Therapeutics, a non-executive director of 10x Genomics and a part-time employee of GlaxoSmithKline. R.E. is an equity holder in EnsoCell. P.K. has consulted for AstraZeneca, UCB, Biomunex and Infinitopes. N.M.P reports consulting fees from Infinitopes. J.S.-R. reports funding from GSK, Pfizer and Sanofi and fees/honoraria from Travere Therapeutics, Stadapharm, Astex, Owkin, Pfizer, Moderna and Grunenthal. A.S. is the recipient of research grants from Roche-Genentech, Abbvie, GSK, Scipher Medicine, Pfizer, Alimentiv, Boehringer Ingelheim and Agomab and has received consulting fees from Genentech, GSK, Pfizer, HotSpot Therapeutics, Alimentiv, Agomab, Goodgut and Orikine. R.E. and S.A.T are inventors on the patent GB2412853.0 filed in the UK, some components of which are related to this work. All other authors declare no competing interests., (© 2024. The Author(s).)

Published
2024
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8. FixNCut: single-cell genomics through reversible tissue fixation and dissociation.

Author

Jiménez-Gracia L, Marchese D, Nieto JC, Caratù G, Melón-Ardanaz E, Gudiño V, Roth S, Wise K, Ryan NK, Jensen KB, Hernando-Momblona X, Bernardes JP, Tran F, Sievers LK, Schreiber S, van den Berge M, Kole T, van der Velde PL, Nawijn MC, Rosenstiel P, Batlle E, Butler LM, Parish IA, Plummer J, Gut I, Salas A, Heyn H, and Martelotto LG

Subjects
Humans, Animals, Mice, Tissue Fixation methods, Reproducibility of Results, Sequence Analysis, RNA methods, Single-Cell Analysis methods, RNA genetics, Genomics methods
Abstract

The use of single-cell technologies for clinical applications requires disconnecting sampling from downstream processing steps. Early sample preservation can further increase robustness and reproducibility by avoiding artifacts introduced during specimen handling. We present FixNCut, a methodology for the reversible fixation of tissue followed by dissociation that overcomes current limitations. We applied FixNCut to human and mouse tissues to demonstrate the preservation of RNA integrity, sequencing library complexity, and cellular composition, while diminishing stress-related artifacts. Besides single-cell RNA sequencing, FixNCut is compatible with multiple single-cell and spatial technologies, making it a versatile tool for robust and flexible study designs., (© 2024. Crown.)

Published
2024
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9. Author Correction: Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Author

Garrido-Trigo A, Corraliza AM, Veny M, Dotti I, Melón-Ardanaz E, Rill A, Crowell HL, Corbí Á, Gudiño V, Esteller M, Álvarez-Teubel I, Aguilar D, Masamunt MC, Killingbeck E, Kim Y, Leon M, Visvanathan S, Marchese D, Caratù G, Martin-Cardona A, Esteve M, Ordás I, Panés J, Ricart E, Mereu E, Heyn H, and Salas A

Published
2024
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10. Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease.

Author

Garrido-Trigo A, Corraliza AM, Veny M, Dotti I, Melón-Ardanaz E, Rill A, Crowell HL, Corbí Á, Gudiño V, Esteller M, Álvarez-Teubel I, Aguilar D, Masamunt MC, Killingbeck E, Kim Y, Leon M, Visvanathan S, Marchese D, Caratù G, Martin-Cardona A, Esteve M, Ordás I, Panés J, Ricart E, Mereu E, Heyn H, and Salas A

Subjects
Humans, Neutrophils, Macrophages, RNA, Inflammatory Bowel Diseases genetics, Crohn Disease genetics
Abstract

Ulcerative colitis and Crohn's disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity., (© 2023. The Author(s).)

Published
2023
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