keyword
https://read.qxmd.com/read/37356564/diazepam-induced-down-regulation-of-the-gaba-a-receptor-%C3%AE-1-subunit-as-mediated-by-the-activation-of-l-type-voltage-gated-calcium-channel-ca-2-protein-kinase-a-signaling-cascade
#1
JOURNAL ARTICLE
Leydi Carolina González Gómez, Nelsy Beatriz Medina, Sara Sanz Blasco, María Clara Gravielle
Benzodiazepines are among the most prescribed drug class worldwide to treat disorders such as anxiety, insomnia, muscle spasticity, and convulsive disorders, and to induce presurgical sedation. Although benzodiazepines exhibit a high therapeutic index and low toxicity in short-term treatments, prolonged administration induces tolerance to most of their therapeutic actions. The mechanism of this tolerance remains unclear. The central actions of benzodiazepines are mediated by binding to GABAA receptors, which mediate most fast inhibitory transmission in the brain...
June 23, 2023: Neuroscience Letters
https://read.qxmd.com/read/37243110/vaccinia-virus-strain-mva-expressing-a-prefusion-stabilized-sars-cov-2-spike-glycoprotein-induces-robust-protection-and-prevents-brain-infection-in-mouse-and-hamster-models
#2
JOURNAL ARTICLE
María M Lorenzo, Alejandro Marín-López, Kevin Chiem, Luis Jimenez-Cabello, Irfan Ullah, Sergio Utrilla-Trigo, Eva Calvo-Pinilla, Gema Lorenzo, Sandra Moreno, Chengjin Ye, Jun-Gyu Park, Alejandro Matía, Alejandro Brun, Juana M Sánchez-Puig, Aitor Nogales, Walther Mothes, Pradeep D Uchil, Priti Kumar, Javier Ortego, Erol Fikrig, Luis Martinez-Sobrido, Rafael Blasco
The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf)...
May 21, 2023: Vaccines
https://read.qxmd.com/read/36902180/the-longitudinal-changes-in-subcutaneous-abdominal-tissue-and-visceral-adipose-tissue-volumetries-are-associated-with-iron-status
#3
JOURNAL ARTICLE
Alejandro Hinojosa-Moscoso, Anna Motger-Albertí, Elena De la Calle-Vargas, Marian Martí-Navas, Carles Biarnés, María Arnoriaga-Rodríguez, Gerard Blasco, Josep Puig, Diego Luque-Córdoba, Feliciano Priego-Capote, José María Moreno-Navarrete, José Manuel Fernández-Real
Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity...
March 1, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/36283859/barriers-for-the-evaluation-of-advanced-therapy-medicines-and-their-translation-to-clinical-practice-umbrella-review
#4
JOURNAL ARTICLE
Lorena Aguilera-Cobos, María Piedad Rosario-Lozano, Angela Ponce-Polo, Juan Antonio Blasco-Amaro, David Epstein
Advanced therapy medicinal products (ATMPs) are a fast-growing field of medicine with wide potential application. Nevertheless, so far, only 19 have obtained European Union (EU) marketing authorisation and only 13 of these have translated successfully into clinical practice. This study conducts an umbrella review to identify the main barriers for the evaluation of ATMPs and their translation into clinical practice across the development lifecycle. 71 systematic reviews were included, of which 50 dealt primarily with effectiveness and safety, 13 with translation from pre-clinical to human subjects...
October 14, 2022: Health Policy
https://read.qxmd.com/read/35842154/monitoring-the-evolution-of-sars-cov-2-on-a-spanish-university-campus-through-wastewater-analysis-a-pilot-project-for-the-reopening-strategy
#5
JOURNAL ARTICLE
Rosa de Llanos, Rocío Cejudo-Marín, Manuela Barneo, Alba Pérez-Cataluña, María Barberá-Riera, Marisa Rebagliato, Juan Bellido-Blasco, Gloria Sánchez, Félix Hernández, Lubertus Bijlsma
Wastewater surveillance is a fast and cost-effective tool that enables tracing of both symptomatic and asymptomatic transmission of SARS-CoV-2. In this paper, a pilot program carried out at the University Jaume I for monitoring the trends of the presence of SARS-CoV-2 in wastewater. To the best of our knowledge, this is the first such project conducted on a university campus in Spain. Wastewater samples (n = 838) were collected when students returned to campus, from October 2020 until August 2021, at a confluence sewer point and at the building level including different academic departments and services, the library, administration offices and the university student residence...
November 1, 2022: Science of the Total Environment
https://read.qxmd.com/read/35807149/effect-of-iron-depletion-by-bloodletting-vs-observation-on-oxidative-stress-biomarkers-of-women-with-functional-hyperandrogenism-taking-a-combined-oral-contraceptive-a-randomized-clinical-trial
#6
JOURNAL ARTICLE
Manuel Luque-Ramírez, Andrés E Ortiz-Flores, María Ángeles Martínez-García, María Insenser, Alejandra Quintero-Tobar, Sara De Lope Quiñones, Elena Fernández-Durán, María Lía Nattero-Chávez, Francisco Álvarez-Blasco, Héctor Francisco Escobar-Morreale
Women with functional hyperandrogenism show both increased markers of oxidative stress and a mild iron overload. Combined oral contraceptives (COC) may worsen redox status in the general population. Since iron depletion ameliorates oxidative stress in other iron overload states, we aimed to address the changes in the redox status of these women as a consequence of COC therapy and of bloodletting, conducting a randomized, controlled, parallel, open-label clinical trial in 33 adult women with polycystic ovary syndrome or idiopathic hyperandrogenism...
July 3, 2022: Journal of Clinical Medicine
https://read.qxmd.com/read/35570127/developing-a-simple-and-practical-decision-model-to-predict-the-risk-of-incident-type-2-diabetes-among-the-general-population-the-di-bet-es-study
#7
JOURNAL ARTICLE
Sergio Martínez-Hervás, María M Morales-Suarez-Varela, Irene Andrés-Blasco, Francisco Lara-Hernández, Isabel Peraita-Costa, José T Real, Ana-Bárbara García-García, F Javier Chaves
AIMS: To develop a simple multivariate predictor model of incident type 2 diabetes in general population. METHODS: Participants were recruited from the Spanish [email protected] cohort study with 2570 subjects meeting all criteria to be included in the at-risk sample studied here. Information was collected using an interviewer-administered structured questionnaire, followed by physical and clinical examination. CHAID algorithm, which collects the information of individuals with and without type 2 diabetes, was used to develop a decision tree based type 2 diabetes prediction model...
August 2022: European Journal of Internal Medicine
https://read.qxmd.com/read/34677285/fast-energy-dependent-scatter-correction-for-list-mode-pet-data
#8
JOURNAL ARTICLE
Juan Manuel Álvarez-Gómez, Joaquín Santos-Blasco, Laura Moliner Martínez, María José Rodríguez-Álvarez
Improvements in energy resolution of modern positron emission tomography (PET) detectors have created opportunities to implement energy-based scatter correction algorithms. Here, we use the energy information of auxiliary windows to estimate the scatter component. Our method is directly implemented in an iterative reconstruction algorithm, generating a scatter-corrected image without the need for sinograms. The purpose was to implement a fast energy-based scatter correction method on list-mode PET data, when it was not possible to use an attenuation map as a practical approach for the scatter degradation...
September 30, 2021: Journal of Imaging
https://read.qxmd.com/read/34594042/the-first-wave-of-the-covid-19-epidemic-in-spain-was-associated-with-early-introductions-and-fast-spread-of-a-dominating-genetic-variant
#9
JOURNAL ARTICLE
Mariana G López, Álvaro Chiner-Oms, Darío García de Viedma, Paula Ruiz-Rodriguez, Maria Alma Bracho, Irving Cancino-Muñoz, Giuseppe D'Auria, Griselda de Marco, Neris García-González, Galo Adrian Goig, Inmaculada Gómez-Navarro, Santiago Jiménez-Serrano, Llúcia Martinez-Priego, Paula Ruiz-Hueso, Lidia Ruiz-Roldán, Manuela Torres-Puente, Juan Alberola, Eliseo Albert, Maitane Aranzamendi Zaldumbide, María Pilar Bea-Escudero, Jose Antonio Boga, Antoni E Bordoy, Andrés Canut-Blasco, Ana Carvajal, Gustavo Cilla Eguiluz, Maria Luz Cordón Rodríguez, José J Costa-Alcalde, María de Toro, Inmaculada de Toro Peinado, Jose Luis Del Pozo, Sebastián Duchêne, Jovita Fernández-Pinero, Begoña Fuster Escrivá, Concepción Gimeno Cardona, Verónica González Galán, Nieves Gonzalo Jiménez, Silvia Hernáez Crespo, Marta Herranz, José Antonio Lepe, Carla López-Causapé, José Luis López-Hontangas, Vicente Martín, Elisa Martró, Ana Milagro Beamonte, Milagrosa Montes Ros, Rosario Moreno-Muñoz, David Navarro, José María Navarro-Marí, Anna Not, Antonio Oliver, Begoña Palop-Borrás, Mónica Parra Grande, Irene Pedrosa-Corral, Maria Carmen Pérez González, Laura Pérez-Lago, Mercedes Pérez-Ruiz, Luis Piñeiro Vázquez, Nuria Rabella, Antonio Rezusta, Lorena Robles Fonseca, Ángel Rodríguez-Villodres, Sara Sanbonmatsu-Gámez, Jon Sicilia, Alex Soriano, María Dolores Tirado Balaguer, Ignacio Torres, Alexander Tristancho, José María Marimón, Mireia Coscolla, Fernando González-Candelas, Iñaki Comas
The coronavirus disease 2019 (COVID-19) pandemic has affected the world radically since 2020. Spain was one of the European countries with the highest incidence during the first wave. As a part of a consortium to monitor and study the evolution of the epidemic, we sequenced 2,170 samples, diagnosed mostly before lockdown measures. Here, we identified at least 500 introductions from multiple international sources and documented the early rise of two dominant Spanish epidemic clades (SECs), probably amplified by superspreading events...
October 2021: Nature Genetics
https://read.qxmd.com/read/34290058/the-antimalarial-mmv688533-provides-potential-for-single-dose-cures-with-a-high-barrier-to-plasmodium-falciparum-parasite-resistance
#10
JOURNAL ARTICLE
James M Murithi, Cécile Pascal, Jade Bath, Xavier Boulenc, Nina F Gnädig, Charisse Flerida A Pasaje, Kelly Rubiano, Tomas Yeo, Sachel Mok, Sylvie Klieber, Paul Desert, María Belén Jiménez-Díaz, Jutta Marfurt, Mélanie Rouillier, Mohammed H Cherkaoui-Rbati, Nathalie Gobeau, Sergio Wittlin, Anne-Catrin Uhlemann, Ric N Price, Grennady Wirjanata, Rintis Noviyanti, Patrick Tumwebaze, Roland A Cooper, Philip J Rosenthal, Laura M Sanz, Francisco Javier Gamo, Jayan Joseph, Shivendra Singh, Sridevi Bashyam, Jean Michel Augereau, Elie Giraud, Tanguy Bozec, Thierry Vermat, Gilles Tuffal, Jean-Michel Guillon, Jérôme Menegotto, Laurent Sallé, Guillaume Louit, Marie-José Cabanis, Marie Françoise Nicolas, Michel Doubovetzky, Rita Merino, Nadir Bessila, Iñigo Angulo-Barturen, Delphine Baud, Lidiya Bebrevska, Fanny Escudié, Jacquin C Niles, Benjamin Blasco, Simon Campbell, Gilles Courtemanche, Laurent Fraisse, Alain Pellet, David A Fidock, Didier Leroy
The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety...
July 21, 2021: Science Translational Medicine
https://read.qxmd.com/read/33081350/viral-related-tools-against-sars-cov-2
#11
REVIEW
Laura Fernandez-Garcia, Olga Pacios, Mónica González-Bardanca, Lucia Blasco, Inés Bleriot, Antón Ambroa, María López, German Bou, Maria Tomás
At the end of 2019, a new disease appeared and spread all over the world, the COVID-19, produced by the coronavirus SARS-CoV-2. As a consequence of this worldwide health crisis, the scientific community began to redirect their knowledge and resources to fight against it. Here we summarize the recent research on viruses employed as therapy and diagnostic of COVID-19: (i) viral-vector vaccines both in clinical trials and pre-clinical phases; (ii) the use of bacteriophages to find antibodies specific to this virus and some studies of how to use the bacteriophages themselves as a treatment against viral diseases; and finally, (iii) the use of CRISPR-Cas technology both to obtain a fast precise diagnose of the patient and also the possible use of this technology as a cure...
October 16, 2020: Viruses
https://read.qxmd.com/read/32847693/acute-phase-glycoprotein-profile-responses-to-different-oral-macronutrient-challenges-influence-of-sex-functional-hyperandrogenism-and-obesity
#12
JOURNAL ARTICLE
Samuel Moncayo, María Insenser, M Ángeles Martínez-García, Rocío Fuertes-Martín, Núria Amigó-Grau, Francisco Álvarez-Blasco, Manuel Luque-Ramírez, Xavier Correig-Blanchar, Héctor F Escobar-Morreale
Acute-phase glycoprotein 1 H-NMR spectroscopy profiles serve as surrogate markers of chronic inflammation in metabolic disorders such as obesity, diabetes and polycystic ovary syndrome (PCOS). The latter is associated with increased height-to-width (H/W) ratios of GlycA and GlycB after fasting, but not to glycoprotein areas, regardless of obesity. We studied the responses to separate glucose, lipid and protein oral challenges of five glycoprotein variables (GlycA, GlycB, and GlycF areas and the GlycA and GlycB H/W ratios) in 17 women with PCOS, 17 control women, and 19 healthy men...
March 2021: Clinical Nutrition
https://read.qxmd.com/read/31936430/tlr2-and-tlr4-surface-and-gene-expression-in-white-blood-cells-after-fasting-and-oral-glucose-lipid-and-protein-challenges-influence-of-obesity-and-sex-hormones
#13
JOURNAL ARTICLE
M Ángeles Martínez-García, Miriam Ojeda-Ojeda, Eulalia Rodríguez-Martín, María Insenser, Samuel Moncayo, Francisco Álvarez-Blasco, Manuel Luque-Ramírez, Héctor F Escobar-Morreale
We studied if macronutrients of the diet have different effects on leukocyte activation, and if these effects are influenced by sex hormones or obesity. We analyzed leukocyte cell surface and gene expression of toll-like receptors 2 and 4 (TLR2 and TLR4) during fasting and after macronutrient loads in women with polycystic ovary syndrome and female and male controls. Fasting TLR2 surface expression in neutrophils was higher in men than in women. Obese subjects presented higher TLR2 gene expression than nonobese individuals, particularly in men...
January 9, 2020: Biomolecules
https://read.qxmd.com/read/31652917/metabolic-cytokines-at-fasting-and-during-macronutrient-challenges-influence-of-obesity-female-androgen-excess-and-sex
#14
JOURNAL ARTICLE
M Ángeles Martínez-García, Samuel Moncayo, María Insenser, Francisco Álvarez-Blasco, Manuel Luque-Ramírez, Héctor F Escobar-Morreale
SCOPE: Cytokines have pleiotropic functions within the organism and their levels may be influenced by obesity, visceral adiposity and sex hormones. Diet composition may also affect their systemic concentrations during fasting and in the postprandial period. Hence, we studied the influence of sex steroids and obesity on the circulating levels of a panel of metabolic cytokines in the fasting state and after single macronutrient challenges. METHODS: On alternate days we submitted 17 women with polycystic ovary syndrome (PCOS) (9 non-obese, 8 obese), 17 non-hyperandrogenic control women (9 non-obese, 8 obese) and 19 control men (10 non-obese, 9 obese) to isocaloric oral glucose, lipid and protein loads...
October 24, 2019: Nutrients
https://read.qxmd.com/read/31469231/screening-protocol-for-the-identification-of-modulators-by-immunofluorescent-cell-based-assay
#15
JOURNAL ARTICLE
Javier Klett, Elena Gómez-Casero, Marinela Méndez-Pertuz, Manuel Urbano-Cuadrado, Diego Megias, María A Blasco, Sonia Martínez, Joaquín Pastor, Carmen Blanco-Aparicio
High-throughput assays are a common strategy for the identification of compounds able to modulate a certain cellular activity. Here, we show an automatized analysis platform for the quantification of nuclear foci as inhibitory effect of compounds on a target protein labeled by fluorescent antibodies. Our experience led us to a fast analysis platform that combines cell-based assays, high-content screening, and confocal microscopy, with an automatic and user-friendly statistical analysis of plate-based assays including positive and negative controls, able to identify inhibitory effect of compounds tested together with the Z-prime and Window of individual plate-based assays to assess the reliability of the results...
January 2020: Chemical Biology & Drug Design
https://read.qxmd.com/read/31060604/testing-the-efficacy-of-integral-cognitive-remediation-increm-in-major-depressive-disorder-study-protocol-for-a-randomized-clinical-trial
#16
RANDOMIZED CONTROLLED TRIAL
Muriel Vicent-Gil, Beatriz Raventós, Eduardo D Marín-Martínez, Sara González-Simarro, Anabel Martínez-Arán, Caterina Del Mar Bonnin, Joan Trujols, Josefina Pérez-Blanco, Javier de Diego-Adeliño, Dolors Puigdemont, Maria Serra-Blasco, Narcís Cardoner, Maria J Portella
BACKGROUND: Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life...
May 6, 2019: BMC Psychiatry
https://read.qxmd.com/read/30975555/postprandial-inflammatory-responses-after-oral-glucose-lipid-and-protein-challenges-influence-of-obesity-sex-and-polycystic-ovary-syndrome
#17
JOURNAL ARTICLE
M Ángeles Martínez-García, Samuel Moncayo, María Insenser, Rafael Montes-Nieto, Elena Fernández-Durán, Francisco Álvarez-Blasco, Manuel Luque-Ramírez, Héctor F Escobar-Morreale
BACKGROUND & AIMS: Most evidence linking the polycystic ovary syndrome (PCOS) with chronic low-grade inflammation has been obtained in the fasting state. We have studied the postprandial inflammatory response to oral glucose, lipid and protein challenges and the possible influences of obesity, sex and PCOS on these responses. METHODS: On alternate days, we submitted 17 women with PCOS (9 non-obese, 8 obese), 17 control women (9 non-obese, 8 obese) and 19 control men (10 non-obese, 9 obese) to isocaloric (300 Kcal) oral macronutrient loads...
March 2020: Clinical Nutrition
https://read.qxmd.com/read/30197603/calcitriol-the-bioactive-metabolite-of-vitamin-d-increases-ventricular-k-currents-in-isolated-mouse-cardiomyocytes
#18
JOURNAL ARTICLE
María Tamayo, Laura Martin-Nunes, Almudena Val-Blasco, Maria J Piedras, María J Larriba, Nieves Gómez-Hurtado, María Fernández-Velasco, Carmen Delgado
Calcitriol, the bioactive metabolite of vitamin D, interacts with the ubiquitously expressed nuclear vitamin D receptor (VDR) to induce genomic effects, but it can also elicit rapid responses via membrane-associated VDR through mechanisms that are poorly understood. The down-regulation of K+ currents is the main origin of electrophysiological remodeling in pathological hypertrophy and heart failure (HF), which can contribute to action potential prolongation and subsequently increase the risk of triggered arrhythmias...
2018: Frontiers in Physiology
https://read.qxmd.com/read/29105287/gut-microbiota-interacts-with-markers-of-adipose-tissue-browning-insulin-action-and-plasma-acetate-in-morbid-obesity
#19
JOURNAL ARTICLE
José María Moreno-Navarrete, Matteo Serino, Vincent Blasco-Baque, Vincent Azalbert, Richard H Barton, Marina Cardellini, Jèssica Latorre, Francisco Ortega, Mònica Sabater-Masdeu, Rémy Burcelin, Marc-Emmanuel Dumas, Wifredo Ricart, Massimo Federici, José Manuel Fernández-Real
SCOPE: To examine the potential relationship among gene expression markers of adipose tissue browning, gut microbiota, and insulin sensitivity in humans. METHODS AND RESULTS: Gut microbiota composition and gene markers of browning are analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue from morbidly obese subjects (n = 34). Plasma acetate is measured through 1 H NMR and insulin sensitivity using euglycemic hyperinsulinemic clamp. Subjects with insulin resistance show an increase in the relative abundance (RA) of the phyla Bacteroidetes and Proteobacteria while RA of Firmicutes is decreased...
February 2018: Molecular Nutrition & Food Research
https://read.qxmd.com/read/27612935/telomere-length-defines-the-cardiomyocyte-differentiation-potency-of-mouse-induced-pluripotent-stem-cells
#20
JOURNAL ARTICLE
Tania Aguado, Francisco J Gutiérrez, Esther Aix, Ralph P Schneider, Giovanna Giovinazzo, María A Blasco, Ignacio Flores
Induced pluripotent stem cells (iPSCs) can be differentiated in vitro and in vivo to all cardiovascular lineages and are therefore a promising cell source for cardiac regenerative therapy. However, iPSC lines do not all differentiate into cardiomyocytes (CMs) with the same efficiency. Here, we show that telomerase-competent iPSCs with relatively long telomeres and high expression of the shelterin-complex protein TRF1 (iPSChighT ) differentiate sooner and more efficiently into CMs than those with relatively short telomeres and low TRF1 expression (iPSClowT )...
February 2017: Stem Cells
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