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133 results on '"López-Gonzálvez, Ángeles"'

11. Metabolomics for searching validated biomarkers in cancer studies: a decade in review.

Author

López-López, Ángeles, López-Gonzálvez, Ángeles, and Barbas, Coral

Abstract

In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways. This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types. Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored. [ABSTRACT FROM AUTHOR]

Published
2024
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17. Mapping early serum proteome signatures of liver regeneration in living donor liver transplant cases

Author

Carmona‐Rodríguez, Lorena, primary, Gajadhar, Aaron S., additional, Blázquez‐García, Irene, additional, Guerrero, Laura, additional, Fernández‐Rojo, Manuel A., additional, Uriarte, Iker, additional, Mamani‐Huanca, Maricruz, additional, López‐Gonzálvez, Ángeles, additional, Ciordia, Sergio, additional, Ramos, Antonio, additional, Herrero, José Ignacio, additional, Fernández‐Barrena, Maite G., additional, Arechederra, María, additional, Berasain, Carmen, additional, Quiroga, Jorge, additional, Sangro, Bruno, additional, Argemi, Josepmaría, additional, Pardo, Fernando, additional, Rotellar, Fernando, additional, López, Daniel, additional, Barbas, Coral, additional, Ávila, Matías A., additional, and Corrales, Fernando J., additional

Published
2023
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19. Energy metabolism as a target for cyclobenzaprine: A drug candidate against Visceral Leishmaniasis

Author

Sao Paulo Research Foundation, Red de Investigación Cooperativa en Enfermedades Tropicales (España), Ministerio de Ciencia e Innovación (España), European Commission, Abengozar, M. A. [0000-0002-2432-3512], Torres-Santos, Eduardo Caio [0000-0003-2240-4519], Treiger Borborema, Samanta Etel [0000-0003-0696-9800], Godzien, Joanna [0000-0002-9477-057X], López-Gonzálvez, Ángeles [0000-0002-6363-7135], Rivas, Luis [0000-0002-2958-3233], Lopes Lima, Marta, Abengozar, M. A., Torres-Santos, Eduardo Caio, Treiger Borborema, Samanta Etel, Godzien, Joanna, López-Gonzálvez, Ángeles, Rivas, Luis, Sao Paulo Research Foundation, Red de Investigación Cooperativa en Enfermedades Tropicales (España), Ministerio de Ciencia e Innovación (España), European Commission, Abengozar, M. A. [0000-0002-2432-3512], Torres-Santos, Eduardo Caio [0000-0003-2240-4519], Treiger Borborema, Samanta Etel [0000-0003-0696-9800], Godzien, Joanna [0000-0002-9477-057X], López-Gonzálvez, Ángeles [0000-0002-6363-7135], Rivas, Luis [0000-0002-2958-3233], Lopes Lima, Marta, Abengozar, M. A., Torres-Santos, Eduardo Caio, Treiger Borborema, Samanta Etel, Godzien, Joanna, López-Gonzálvez, Ángeles, and Rivas, Luis

Abstract

Leishmaniases have a broad spectrum of clinical manifestations, ranging from a cutaneous to a progressive and fatal visceral disease. Chemotherapy is nowadays the almost exclusive way to fight the disease but limited by its scarce therapeutic arsenal, on its own compromised by adverse side effects and clinical resistance. Cyclobenzaprine (CBP), an FDA-approved oral muscle relaxant drug has previously demonstrated in vitro and in vivo activity against Leishmania sp., but its targets were not fully unveiled. This study aimed to define the role of energy metabolism as a target for the leishmanicidal mechanisms of CBP. Methodology to assess CBP leishmanicidal mechanism variation of intracellular ATP levels using living Leishmania transfected with a cytoplasmic luciferase. Induction of plasma membrane permeability by assessing depolarization with DiSBAC(2)3 and entrance of the vital dye SYTOX® Green. Mitochondrial depolarization by rhodamine 123 accumulation. Mapping target site within the respiratory chain by oxygen consumption rate. Reactive oxygen species (ROS) production using MitoSOX. Morphological changes by transmission electron microscopy. CBP caused on L. infantum promastigotes a decrease of intracellular ATP levels, with irreversible depolarization of plasma membrane, the collapse of the mitochondrial electrochemical potential, mild uncoupling of the respiratory chain, and ROS production, with ensuing intracellular Ca2+ imbalance and DNA fragmentation. Electron microscopy supported autophagic features but not a massive plasma membrane disruption. The severe and irreversible mitochondrial damage induced by CBP endorsed the bioenergetics metabolism as a relevant target within the lethal programme induced by CBP in Leishmania. This, together with the mild-side effects of this oral drug, endorses CBP as an appealing novel candidate as a leishmanicidal drug under a drug repurposing strategy.

Published
2022

22. Contributors

Author

Alexander, James L., primary, Barbas, Coral, additional, Bonner, Frank W., additional, Brennan, Lorraine, additional, Fussell, Julia C., additional, Cameron, Simon J., additional, Castagné, Raphaële, additional, Chadeau-Hyam, Marc, additional, Climaco Pinto, Rui, additional, Deda, Olga, additional, Dehghan, Abbas, additional, Dunn, Warwick B., additional, Ebbels, Timothy M.D., additional, Elliott, Paul, additional, Evangelou, Evangelos, additional, Everett, Jeremy R., additional, Galea, Dieter, additional, Gao, Jianliang, additional, García, Antonia, additional, Gika, Helen, additional, Glen, Robert C., additional, Godzien, Joanna, additional, Holmes, Elaine, additional, Hoyles, Lesley, additional, Kelly, Frank J., additional, Karaman, Ibrahim, additional, Kinross, James M., additional, Laponogov, Ivan, additional, Lewis, Matthew R., additional, Lindon, John C., additional, López-Gonzálvez, Ángeles, additional, Maslen, Lynn, additional, Nicholson, Jeremy K., additional, O’Neill, Kevin S., additional, Parkinson, John A., additional, Pearce, Jake T.M., additional, Plumb, Robert S., additional, Posma, Joram M., additional, Raikos, Nikolaos, additional, Sadawi, Noureddin, additional, Salek, Reza M., additional, Swann, Jonathan, additional, Takats, Zoltan, additional, Theodoridis, Georgios, additional, Tzoulaki, Ioanna, additional, Vaqas, Babar, additional, Veselkov, Kirill, additional, and Wilson, Ian D., additional

Published
2019
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29. Molecular basis of the leishmanicidal activity of the antidepressant sertraline as a drug repurposing candidate

Author

Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Sao Paulo Research Foundation, Lima, Marta L. [0000-0003-1993-9985], Abengozar, M. A. [0000-0002-2432-3512], Nácher-Vázquez, Montserrat [0000-0001-8355-8373], Barbas, Coral [0000-0003-4722-491X], Tempone, Andre G. [0000-0003-2559-7344], López-Gonzálvez, Ángeles [0000-0002-6363-7135], Rivas, Luis [0000-0002-2958-3233], Lima, Marta L., Abengozar, M. A., Nácher-Vázquez, Montserrat, Martinez-Alcazar, Maria P., Barbas, Coral, Tempone, Andre G., López-Gonzálvez, Ángeles, Rivas, Luis, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Sao Paulo Research Foundation, Lima, Marta L. [0000-0003-1993-9985], Abengozar, M. A. [0000-0002-2432-3512], Nácher-Vázquez, Montserrat [0000-0001-8355-8373], Barbas, Coral [0000-0003-4722-491X], Tempone, Andre G. [0000-0003-2559-7344], López-Gonzálvez, Ángeles [0000-0002-6363-7135], Rivas, Luis [0000-0002-2958-3233], Lima, Marta L., Abengozar, M. A., Nácher-Vázquez, Montserrat, Martinez-Alcazar, Maria P., Barbas, Coral, Tempone, Andre G., López-Gonzálvez, Ángeles, and Rivas, Luis

Abstract

Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress in L. infantum promastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as shortage of intracellular amino acids used as metabolic fuel by Leishmania Sertraline killed Leishmania through a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy.

Published
2018

31. Leishmanicidal mechanism of sertraline

Author

Lima, Marta L., Abengozar, M. A., Nácher-Vázquez, Montserrat, Martinez-Alcazar, Maria P., Barbas, Coral, Tempone, Andre G., López-Gonzálvez, Ángeles, Rivas, Luis, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Consejo Superior de Investigaciones Científicas (España), Sao Paulo Research Foundation, Lima, Marta L. [0000-0003-1993-9985], Abengozar, M. A. [0000-0002-2432-3512], Nácher-Vázquez, Montserrat [0000-0001-8355-8373], Barbas, Coral [0000-0003-4722-491X], Tempone, Andre G. [0000-0003-2559-7344], López-Gonzálvez, Ángeles [0000-0002-6363-7135], and Rivas, Luis [0000-0002-2958-3233]

Subjects
Sertraline, parasitic diseases, Drug repurposing, Metabolomics
Abstract

42 p.-8 fig. Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in Leishmania were poorly defined. In order to get a detailed insight into the leishmanicidal mechanism of sertraline on Leishmania infantum, unbiased multiplatform metabolomics and transmission electron microscopy were combined with a focused insight into the sertraline effects on bioenergetics metabolism of the parasite. Sertraline induced respiration uncoupling, a significant decrease of intracellular ATP level, and oxidative stress in L. infantum promastigotes. Metabolomics evidenced an extended metabolic disarray caused by sertraline. This encompasses a remarkable variation of the levels of thiol-redox and polyamine biosynthetic intermediates, as well as shortage of intracellular amino acids used as metabolic fuel by Leishmania Sertraline killed Leishmania through a multitarget mechanism of action, tackling essential metabolic pathways of the parasite. As such, sertraline is a valuable candidate for visceral leishmaniasis treatment under a drug repurposing strategy. This work was supported by grants of the Fondo de Investigaciones Sanitarias-ISCIII-FEDER (PI12-02706), and (RD16/0027/0010, Red de Enfermedades Tropicales, subprogram RETICS del Plan Estatal de I+D+i (2013-2016) co-financed with FEDER funds, SAF2015-65740-R, and CSIC PIE 201620E038 to L. R., São Paulo State Research Foundation (FAPESP 2015/23403-9 to A. G.T.); EADS-CASA/ Brazilian Air Force (FAB) mobility program to M.L.L., and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) to M.L.L.

Published
2018

32. Metabolic clustering analysis as a strategy for compound selection in the drug discovery pipeline for leishmaniasis

Author

Armitage, Emily G., Godzien, Joanna, Peña, Imanol, López-Gonzálvez, Ángeles, Angulo, Santiago, Gradillas, Ana, Alonso-Herranz, Vanesa, Martín, Julio, Fiandor, Jose M., Barrett, Michael P., Gabarro, Raquel, and Barbas, Coral

Subjects
parasitic diseases
Abstract

A lack of viable hits, increasing resistance, and limited knowledge on mode of action is hindering drug discovery for many diseases. To optimize prioritization and accelerate the discovery process, a strategy to cluster compounds based on more than chemical structure is required. We show the power of metabolomics in comparing effects on metabolism of 28 different candidate treatments for Leishmaniasis (25 from the GSK Leishmania box, two analogues of Leishmania box series, and amphotericin B as a gold standard treatment), tested in the axenic amastigote form of Leishmania donovani. Capillary electrophoresis–mass spectrometry was applied to identify the metabolic profile of Leishmania donovani, and principal components analysis was used to cluster compounds on potential mode of action, offering a medium throughput screening approach in drug selection/prioritization. The comprehensive and sensitive nature of the data has also made detailed effects of each compound obtainable, providing a resource to assist in further mechanistic studies and prioritization of these compounds for the development of new antileishmanial drugs.

Published
2018

34. Mapping Alterations Induced by Long-Term Axenic Cultivation of Leishmania amazonensis Promastigotes With a Multiplatform Metabolomic Fingerprint Approach

Author

Crepaldi, Frederico, primary, de Toledo, Juliano Simões, additional, do Carmo, Anderson Oliveira, additional, Ferreira Marques Machado, Leopoldo, additional, de Brito, Daniela Diniz Viana, additional, Serufo, Angela Vieira, additional, Almeida, Ana Paula Martins, additional, de Oliveira, Leandro Gonzaga, additional, Ricotta, Tiago Queiroga Nery, additional, Moreira, Douglas de Souza, additional, Murta, Silvane Maria Fonseca, additional, Diniz, Ariane Barros, additional, Menezes, Gustavo Batista, additional, López-Gonzálvez, Ángeles, additional, Barbas, Coral, additional, and Fernandes, Ana Paula, additional

Published
2019
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35. Recent Developments along the Analytical Process for Metabolomics Workflows

Author

González-Riano, Carolina, primary, Dudzik, Danuta, additional, Garcia, Antonia, additional, Gil-de-la-Fuente, Alberto, additional, Gradillas, Ana, additional, Godzien, Joanna, additional, López-Gonzálvez, Ángeles, additional, Rey-Stolle, Fernanda, additional, Rojo, David, additional, Ruperez, Francisco J., additional, Saiz, Jorge, additional, and Barbas, Coral, additional

Published
2019
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36. Repression of drought-induced cysteine-protease genes alters barley leaf structure and responses to abiotic and biotic stresses

Author

Gómez Sánchez, Andrea, González Melendi, Pablo, Santamaría Fernández, María Estrella, Arbona Mengual, Vicente, López Gonzálvez, Ángeles, García, Antonia, Hensel, Goetz, Kumlehn, Jochen, Martinez Muñoz, Manuel, Diaz Rodriguez, Isabel, Gómez Sánchez, Andrea, González Melendi, Pablo, Santamaría Fernández, María Estrella, Arbona Mengual, Vicente, López Gonzálvez, Ángeles, García, Antonia, Hensel, Goetz, Kumlehn, Jochen, Martinez Muñoz, Manuel, and Diaz Rodriguez, Isabel

Abstract

To survive under water deficiency, plants alter gene expression patterns, make structural and physiological adjustments, and optimize the use of water. Rapid degradation and turnover of proteins is required for effective nutrient recycling. Here, we examined the transcriptional responses of the C1A cysteine protease family to drought in barley and found that four genes were up-regulated in stressed plants. Knock-down lines for the protease-encoding genes HvPap-1 and HvPap-19 showed unexpected changes in leaf cuticle thickness and stomatal pore area. The efficiency of photosystem II and the total amount of proteins were almost unaltered in stressed transgenic plants while both parameters decreased in stressed wild-type plants. Although the patterns of proteolytic activities in the knock-down lines did not change, the amino acid accumulation increased in response to drought, concomitant with a higher ABA content. Whilst jasmonic acid (JA) and JA-Ile concentrations increased in stressed leaves of the wild-type and the HvPap-1 knock-down lines, their levels were lower in the HvPap-19 knock-down lines, suggesting the involvement of a specific hormone interaction in the process. Our data indicate that the changes in leaf cuticle thickness and stomatal pore area had advantageous effects on leaf defense against fungal infection and mite feeding mediated by Magnaporthe oryzae and Tetranychus urticae, respectively.

Published
2019

39. Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine

Author

Armitage, Emily G., primary, Alqaisi, Amjed Q. I., additional, Godzien, Joanna, additional, Peña, Imanol, additional, Mbekeani, Alison J., additional, Alonso-Herranz, Vanesa, additional, López-Gonzálvez, Ángeles, additional, Martín, Julio, additional, Gabarro, Raquel, additional, Denny, Paul W., additional, Barrett, Michael P., additional, and Barbas, Coral, additional

Published
2018
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40. Metabolomics as a tool to evaluate the toxicity of formulations containing amphotericin B, an antileishmanial drug† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6tx00253f

Author

Santos, Délia C. M., Lima, Marta L., Toledo, Juliano S., Fernandes, Paula A., Aguiar, Marta M. G., López-Gonzálvez, Ángeles, Ferreira, Lucas A. M., Fernandes, Ana Paula, and Barbas, Coral

Subjects
Chemistry, urogenital system, animal diseases, parasitic diseases, technology, industry, and agriculture, bacterial infections and mycoses
Abstract

Amphotericin B (AmB) is a drug of choice against life-threatening systemic fungal infections and an alternative therapy for the treatment of all forms of leishmaniasis. It is known that AmB and its conventional formulation cause renal damage; however, the lipid formulations can reduce these effects. The aim of the present study was to identify metabolic changes in mice treated with two different AmB formulations, a nanoemulsion (NE) (lipid system carrier) loaded with AmB and the conventional formulation (C-AmB). For this purpose, metabolic fingerprinting represents a valuable strategy to monitor, in a non-targeted manner, the changes that are at the base of the toxicity mechanism of AmB. Plasma samples of BALB-c mice were collected after treatment with 3 alternate doses of AmB at 1 mg kg

Published
2016

45. Inverse colloidal crystal membranes for hydrophobic interaction membrane chromatography

Author

Wenz, Christian, primary, Barbas, Coral, additional, López-Gonzálvez, Ángeles, additional, Garcia, Antonia, additional, Benavente, Fernando, additional, Sanz-Nebot, Victoria, additional, Blanc, Tim, additional, Freckleton, Gordon, additional, Britz-McKibbin, Philip, additional, Shanmuganathan, Meera, additional, de l′Escaille, Francois, additional, Far, Johann, additional, Haselberg, Rob, additional, Huang, Sean, additional, Huhn, Carolin, additional, Pattky, Martin, additional, Michels, David, additional, Mou, Si, additional, Yang, Feng, additional, Neusuess, Christian, additional, Tromsdorf, Nora, additional, Baidoo, Edward E.K., additional, Keasling, Jay D., additional, and Park, SungAe Suhr, additional

Published
2015
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46. Capillary electrophoresis reveals polyamine metabolism modulation in Leishmania (Leishmania) amazonensis wild‐type and arginase‐knockout mutants under arginine starvation

Author

Castilho‐Martins, Emerson A., primary, Canuto, Gisele A. B., additional, Muxel, Sandra Marcia, additional, daSilva, Maria Fernanda Laranjeira, additional, Floeter‐Winter, Lucile Maria, additional, del Aguila, Carmen, additional, López‐Gonzálvez, Ángeles, additional, and Barbas, Coral, additional

Published
2015
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47. Interlaboratory study to evaluate the robustness of capillary electrophoresis-mass spectrometry for peptide mapping

Author

Wenz, Christian, primary, Barbas, Coral, additional, López-Gonzálvez, Ángeles, additional, Garcia, Antonia, additional, Benavente, Fernando, additional, Sanz-Nebot, Victoria, additional, Blanc, Tim, additional, Freckleton, Gordon, additional, Britz-McKibbin, Philip, additional, Shanmuganathan, Meera, additional, de l'Escaille, Francois, additional, Far, Johann, additional, Haselberg, Rob, additional, Huang, Sean, additional, Huhn, Carolin, additional, Pattky, Martin, additional, Michels, David, additional, Mou, Si, additional, Yang, Feng, additional, Neusuess, Christian, additional, Tromsdorf, Nora, additional, Baidoo, Edward E.K., additional, Keasling, Jay D., additional, and Park, SungAe Suhr, additional

Published
2015
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