27 research outputs found

    Long-term immune response accompanies clinical outcomes in severe asthmatics treated with anti-IL-5/IL-5R biologics

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    This work was supported by ISCIII - Instituto de Salud Carlos III, FIS (Fondo de Investigación Sanitaria - Spanish Health Research Fund) grants PI21/00896 and FI19/00067; Ciber de Enfermedades Respiratorias (CIBERES); SEAIC grants 22A07; BASEAS STUDY (Basophils in EosinophilicAsthma) Study Code ESR-20-20764 AstraZeneca International; Comunidad de Madrid grant PEJ2021-AI_BMD-22320 and FEDER funds (Fondo Europeo de Desarrollo Regiona

    Serum micrornas as tool to predict early response to benralizumab in severe eosinophilic asthma

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    Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.This manuscript was funded by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation funds, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1

    Analyzing and Modeling Real-World Phenomena with Complex Networks: A Survey of Applications

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    The success of new scientific areas can be assessed by their potential for contributing to new theoretical approaches and in applications to real-world problems. Complex networks have fared extremely well in both of these aspects, with their sound theoretical basis developed over the years and with a variety of applications. In this survey, we analyze the applications of complex networks to real-world problems and data, with emphasis in representation, analysis and modeling, after an introduction to the main concepts and models. A diversity of phenomena are surveyed, which may be classified into no less than 22 areas, providing a clear indication of the impact of the field of complex networks.Comment: 103 pages, 3 figures and 7 tables. A working manuscript, suggestions are welcome

    Instalaciones para el resguardo, investigación y disfrute de los recursos naturales del Parque Nacional Diriá

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    Proyecto de graduación (licenciatura en arquitectura)UCR::Vicerrectoría de Docencia::Ingeniería::Facultad de Ingeniería::Escuela de Arquitectur

    Metal-free redox-active diphenylpyrenediimides: A comparison between the photocatalytic performance of molecular and polymeric catalysts

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    Herein we described a donor–acceptor porous conjugated polydiphenylpyreneimide (DPPy-PI) with high thermal stability (530 °C) and surface area of 710 m.g prepared by condensation of 3,8-diphenylpyrene-1,2,6,7-tetracarboxylic dianhydride (DPPyDA) and tris(4-aminophenyl)benzene and a series of pyrenediimides (DPPy-DIs) as molecular references for comparative purposes. To evaluate the effect of the photoactive pyrene unit the polydiphenylperyleneimide (DPP-PI) having perylene units was also prepared. DPPy-PI has shown to see an efficient metal-free heterogeneous photocatalyst in the selective oxidation of aromatic sulfides and for Diels-Alder cycloadditions reaching almost full conversions with low reaction times and high selectivity that can be reused for at least fifteen cycles without significant loss of catalytic activity. Characterization data reveals that imide radicals are the important active intermediates during the redox processes of these PIs.Authors acknowledge to Grants PID2020-112590GB-C22 and PID2019-107675RB-I00 funded by MCIN/AEI/10.13039/501100011033. We acknowledge Laura San Miguel for the first tests of catalytic activity

    Changes in serum micrornas after anti-il-5 biological treatment of severe asthma

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    There is currently enough evidence to think that miRNAs play a role in several key points in asthma, including diagnosis, severity of the disease, and response to treatment. Cells release different types of lipid double-membrane vesicles into the extracellular microenvironment, including exosomes, which function as very important elements in intercellular communication. They are capable of distributing genetic material, mRNA, mitochondrial DNA, and microRNAs (miRNAs). Serum miRNA screening was performed in order to analyze possible changes in serum miRNAs in 10 patients treated with reslizumab and 6 patients with mepolizumab after 8 weeks of treatment. The expression of miR-338-3p was altered after treatment (p < 0.05), although no significant differences between reslizumab and mepolizumab were found. Bioinformatic analysis showed that miR-338-3p regulates important pathways in asthma, such as the MAPK and TGF-β signaling pathways and the biosynthesis/degradation of glucans (p < 0.05). However, it did not correlate with an improvement in lung function. MiRNA-338-3p could be used as a biomarker of early response to reslizumab and mepolizumab in severe eosinophilic asthmatic patients. In fact, this miRNA could be involved in airway remodeling, targeting genes related to MAPK and TGF-β signaling pathways.This research was funded by Fondo de Investigación Sanitaria (FIS) and FEDER (Fondo Europeo de Desarrollo Regional; PI18/00044, and FI16/00036), CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1)

    EAACI Molecular Allergology User's Guide 2.0

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    Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE-mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE-mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well-defined, highly pure molecules for component-resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the "EAACI Molecular Allergology User's Guide" (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state-of-the-art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure
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