412 research outputs found

    Oregano essential oil-pectin edible films as anti-quorum sensing and food antimicrobial agents

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    Edible films can be used as carriers for antimicrobial compounds to assure food safety andquality; in addition, pathogenesis of food bacteria is related to a cell to cell communicationmechanism calledquorum sensing(QS). Oregano essential oil (OEO) has proved to beuseful as food antimicrobial; however, its foodapplications can be compromised by thevolatile character of its active constituents.Therefore, formulation of edible films containingOEO can be an alternative to improve its food usages. QS inhibitory activity of OEO andpectin-OEO films was evaluated usingChromobacterium violaceumas bacterial model.Additionally, antibacterial activity was tested againstEscherichia coliO157:H7,SalmonellaCholeraesuis,Staphylococcus aureus,andListeria monocytogenes. OEO was effective toinhibit bacterial growth at MIC of 0.24 mg/mL for all tested bacteria and MBC of 0.24,0.24, 0.48, and 0.24 mg/mL againstE. coliO157:H7,S.Choleraesuis,S. aureus, andL.monocytogenes, respectively. Pectin-films incorporated with 36.1 and 25.9 mg/mL of OEOshowed inhibition diameters of 16.3 and 15.2 mm forE. coliO157:H7; 18.1 and 24.2 mm forS.Choleraesuis; 20.8 and 20.3 mm forS. aureus; 21.3 and 19.3 mm forL. monocytogenes,respectively. Pectin-OEO film (15.7 mg/mL) was effective againstE. coliO157:H7 (9.3 mm),S. aureus(9.7 mm), andL. monocytogenes(9.2 mm), but not forS.Choleraesuis. Allconcentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO films(15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed as inhibition ofviolacein production byC. violaceum. Additionally, the application of pectin-OEO films waseffective reducing total coliforms, yeast, and molds of shrimp and cucumber slices storedat 4◦C during 15 d.These results demonstrated the potential of pectin films enriched withOEO as food related microorganisms and QS inhibitorsFil: Alvarez, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería En Alimentos; ArgentinaFil: Ortega Ramirez, Luis Alberto. Centro de Investigación en Alimentación y Desarrollo. Hermosillo; MéxicoFil: Gutierrez Pacheco, Maria Melissa. Centro de Investigación en Alimentación y Desarrollo. Hermosillo; MéxicoFil: Bernal Mercado, Thalia. Centro de Investigación en Alimentación y Desarrollo. Hermosillo; MéxicoFil: Rodriguez Garcia, Isela. Centro de Investigación en Alimentación y Desarrollo. Hermosillo; MéxicoFil: Ponce, Alejandra Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería En Alimentos; ArgentinaFil: Moreira, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería En Alimentos; ArgentinaFil: Roura, Sara Ines. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Departamento de Ingeniería Química. Grupo de Investigación en Ingeniería En Alimentos; ArgentinaFil: Ayala Zavala, Jesús Fernando. Centro de Investigación en Alimentación y Desarrollo. Hermosillo; Méxic

    BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy

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    Glycolysis; Melanomas; Targeted therapyGlucólisis; Melanomas; Terapia dirigidaGlucòlisi; Melanomes; Teràpia dirigidaNRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.This work was funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF, “A way to make Europe”/“Investing in your future”) PI14/0375-Fondos FEDER J.A.R., PI17/00043-Fondos FEDER; J.A.R., PI20/0384-Fondos FEDER; J.A.R., Euronanomed2-ISCIII (AC16/00019)-Fondos FEDER; J.A.R., Asociación Española Contra el Cancer (AECC-GCB15152978SOEN) (supported P.G.M., K.M.); J.A.R., Ramón Areces Foundation (supported K.M. and research); J.A.R. (PI17/00412)-Fondos FEDER; R.B., A.M., A.N.S. We thank A. Zorzano’s laboratory for technical assistance and performance of Seahorse technology

    Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis.

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    PURPOSE Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs. EXPERIMENTAL DESIGN ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models. RESULTS ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis. CONCLUSIONS Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.We apologize to those authors whose work could not be cited due to size limitations. We thank Dr. Eduard Serra, Dr. Conxi Lázaro and Dr. David Lyden for their support in the project. We also thank Héctor Tejero for his help in analyzing RNA-seq data. Dr. Peinado laboratory is funded by US Department of Defense (W81XWH-16-1-0131), Agencia Estatal de Investigación/Ministerio de Ciencia e Innovación (AEI/MCIN) (PID2020-118558RB-I00/AEI/10.13039/501100011033), Fundación Proyecto Neurofibromatosis, European Union’s Horizon 2020 research and innovation programme “proEVLifeCycle” under the Marie Skłodowska-Curie grant agreement No 860303, and Fundación Científica AECC. We are also grateful for the support of the Ministerio de Universidades (Programa de Formación de Profesorado Universitario (FPU)) for the fellowship FPU016/05356 awarded to T. González-Muñoz and to the Translational NeTwork for the CLinical application of Extracellular VesicleS (TeNTaCLES) RED2018-102411-T(AEI/10.13039/501100011033). A. Di Giannatale was supported during this work by a research gran Nuovo-Soldati Foundation. The CNIO, certified as Severo Ochoa Excellence Centre, is supported by the Spanish Government through the Instituto de Salud Carlos III.N

    Solution-based synthesis and processing of Sn- and Bi-doped Cu₃SbSe₄ nanocrystals, nanomaterials and ring-shaped thermoelectric generators

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    Copper-based chalcogenides that comprise abundant, low-cost, and environmental friendly elements are excellent materials for a number of energy conversion applications, including photovoltaics, photocatalysis, and thermoelectrics (TE). In such applications, the use of solution-processed nanocrystals (NCs) to produce thin films or bulk nanomaterials has associated several potential advantages, such as high material yield and throughput, and composition control with unmatched spatial resolution and cost. Here we report on the production of Cu₃SbSe₄ (CASe) NCs with tuned amounts of Sn and Bi dopants. After proper ligand removal, as monitored by nuclear magnetic resonance and infrared spectroscopy, these NCs were used to produce dense CASe bulk nanomaterials for solid state TE energy conversion. By adjusting the amount of extrinsic dopants, dimensionless TE figures of merit (ZT) up to 1.26 at 673 K were reached. Such high ZT values are related to an optimized carrier concentration by Sn doping, a minimized lattice thermal conductivity due to efficient phonon scattering at point defects and grain boundaries, and to an increase of the Seebeck coefficient obtained by a modification of the electronic band structure with Bi doping. Nanomaterials were further employed to fabricate ring-shaped TE generators to be coupled to hot pipes, which provided 20 mV and 1 mW per TE element when exposed to a 160 °C temperature gradient. The simple design and good thermal contact associated with the ring geometry and the potential low cost of the material solution processing may allow the fabrication of TE generators with short payback times

    Impact of COVID-19 Confinement on Physical Activity and Sedentary Behaviour in Spanish University Students: Role of Gender

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    [EN] During the COVID-19 pandemic, entire populations were instructed to live in home-confinement to prevent the expansion of the disease. Spain was one of the countries with the strictest conditions, as outdoor physical activity was banned for nearly two months. This study aimed to analyse the changes in physical activity and sedentary behaviours in Spanish university students before and during the confinement by COVID-19 with special focus on gender. We also analysed enjoyment, the tools used and motivation and impediments for doing physical activity. An online questionnaire, which included the International Physical Activity Questionnaire Short Form and certain "ad hoc" questions, was designed. Students were recruited by distributing an invitation through the administrative channels of 16 universities and a total of 13,754 valid surveys were collected. Overall, university students reduced moderate (-29.5%) and vigorous (-18.3%) physical activity during the confinement and increased sedentary time (+52.7%). However, they spent more time on high intensity interval training (HIIT) (+18.2%) and mind-body activities (e.g., yoga) (+80.0%). Adaptation to the confinement, in terms of physical activity, was handled better by women than by men. These results will help design strategies for each gender to promote physical activity and reduce sedentary behaviour during confinement periods.S

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

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    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

    Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

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    La garantía de calidad en el ámbito universitario puede considerarse como la atención sistemática, estructurada y continua a las titulaciones ofertadas. La garantía de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y así cumplir con la obligación que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfacción de los colectivos implicados en el proceso de enseñanza-aprendizaje (Profesorado, Estudiantes y PAS)
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