Growth Hormone Reprograms Macrophages toward an Anti-Inflammatory and Reparative Profile in an MAFB-Dependent Manner

Growth hormone (GH), a pleiotropic hormone secreted by the pituitary gland, regulates immune and inflammatory responses. In this study, we show that GH regulates the phenotypic and functional plasticity of macrophages both in vitro and in vivo. Specifically, GH treatment of GM-CSF–primed monocyte–derived macrophages promotes a significant enrichment of anti-inflammatory genes and dampens the proinflammatory cytokine profile through PI3K-mediated downregulation of activin A and upregulation of MAFB, a critical transcription factor for anti-inflammatory polarization of human macrophages. These in vitro data correlate with improved remission of inflammation and mucosal repair during recovery in the acute dextran sodium sulfate–induced colitis model in GH-overexpressing mice. In this model, in addition to the GH-mediated effects on other immune cells, we observed that macrophages from inflamed gut acquire an anti-inflammatory/reparative profile. Overall, these data indicate that GH reprograms inflammatory macrophages to an anti-inflammatory phenotype and improves resolution during pathologic inflammatory responses.This work was supported in part by grants from the Spanish Ministry of Science, Innovation and Universities (SAF2017-82940-R Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional (AEI/FEDER), Unión Europea [UE] [to M.M.], SAF2017-83785-R AEI/FEDER, UE [to Á.L.C.] and FJCI-2016-29990 AEI/FEDER, UE [to B.S.P.]), from the Redes Temáticas de Investigación Cooperativa en Salud Program of Instituto de Salud Carlos III (RD12/0012/0006 and RD12/0012/0007, Red de Investigación en Inflamación y Enfermedades Reumáticas), and the Regional Government of Madrid (B2017/BMD-3804 [to C.M.-A.])

¿Qué saben de los ODS los alumnos de la UPV? Análisis preliminar

[EN] Universities play an important role in accomplishing the so-called Sustainable Development Goals (SDGs), equiping students with knowledge and skills to address the sustainability challenges through the teaching-learning process. The implementation of knowledge of the SDGs among teachers and students is urgent, being thus essential to assess their previous knowledge level. In order to evaluate the previous knowledge about the SDGs of students of different degrees and masters of the Universitat Politècnica de València (UPV), a questionnaire was designed. The questionnaire was answered by 425 students. The analysis of the answers revealed the need to review some of the questions, as well as the convenience of including others that collect evidences on sources of information and professional and personal implications of the SDGs. In general, the results showed a high level of knowledge about the SDGs. The differences observed between subjects could be related to their context within the degree, as well as the profile of the student in each of them. The information obtained will also help in the design of activities for the training of students of different subjects in relation to the SDGs.[ES] Las universidades juegan un papel importante en el cumplimiento de los Objetivos de Desarrollo Sostenible (ODS), ya que en el proceso de enseñanza-aprendizaje equipan al alumnado con conocimiento y habilidades para abordar los desafíos de la sostenibilidad. Urge la puesta en marcha del conocimiento de los ODS entre profesorado y alumnado, resultando fundamental conocer su nivel previo de conocimiento. Con el fin de evaluar el conocimiento previo sobre los ODS del alumnado de diferentes grados y másteres de la Universitat Politècnica de València (UPV), se diseñó un cuestionario, que fue respondido por un total de 425 alumnos/as de distintas titulaciones de la UPV. El análisis de las respuestas reveló la necesidad de revisar alguna de las preguntas, así como la conveniencia de incluir otras que recojan datos sobre fuentes de información e implicaciones profesionales y personales de los ODS. En general, los resultados mostraron un nivel elevado de conocimiento sobre ODS. Las diferencias observadas entre asignaturas podrían estar relacionadas con su contexto dentro de la titulación, así como con el perfil del alumnado de cada una de ellas. La información obtenida se orientará al diseño de actividades para la formación del alumnado de las distintas asignaturas en relación a los ODS.La publicación de este trabajo ha sido parcialmente financiada por el proyecto de innovación educativa (PIME 20-21/224) concedido por el Vicerrectorado de Estudios, Calidad y Acreditación de la Universitat Politècnica de València (UPV). Los autores agradecen también el apoyo proporcionado por el Instituto de Ciencias de la Educación (ICE) de la UPV.Lull Noguera, C.; Pérez De Castro, AM.; Leiva Brondo, M.; Atarés Huerta, A.; Lajara De Camilleri, N.; Llinares Palacios, JV.; Pérez Esteve, E.... (2021). ¿Qué saben de los ODS los alumnos de la UPV? Análisis preliminar. En IN-RED 2021: VII Congreso de Innovación Edicativa y Docencia en Red. Editorial Universitat Politècnica de València. 1106-1119. https://doi.org/10.4995/INRED2021.2021.137811106111

MAFB shapes human monocyte-derived macrophage response to SARS-CoV-2 and controls severe COVID-19 biomarker expression

22 p.-6 fig.1 graph. abst.Monocyte-derived macrophages, the major source of pathogenic macrophages in COVID-19, are oppositely instructed by macrophage CSF (M-CSF) or granulocyte macrophage CSF (GM-CSF), which promote the generation of antiinflammatory/immunosuppressive MAFB+ (M-MØ) or proinflammatory macrophages (GM-MØ), respectively. The transcriptional profile of prevailing macrophage subsets in severe COVID-19 led us to hypothesize that MAFB shapes the transcriptome of pulmonary macrophages driving severe COVID-19 pathogenesis. We have now assessed the role of MAFB in the response of monocyte-derived macrophages to SARS-CoV-2 through genetic and pharmacological approaches, and we demonstrate that MAFB regulated the expression of the genes that define pulmonary pathogenic macrophages in severe COVID-19. Indeed, SARS-CoV-2 potentiated the expression of MAFB and MAFB-regulated genes in M-MØ and GM-MØ, where MAFB upregulated the expression of profibrotic and neutrophil-attracting factors. Thus, MAFB determines the transcriptome and functions of the monocyte-derived macrophage subsets that underlie pulmonary pathogenesis in severe COVID-19 and controls the expression of potentially useful biomarkers for COVID-19 severity.This work was supported by grant PID2020-114323RB-I00 from Ministerio de Ciencia e Innovación to ALC; “Ayudas FUNDACIÓN BBVA a equipos de investigación científica SARS-CoV-2 y COVID-19” to MAV and ALC; Dirección General de Innovación e Investigación Tecnológica de la Comunidad de Madrid (RETARACOVID, P2022/BMD-7274) to ALC, APK, EFR, and RD; Instituto de Salud Carlos III (grant PI20/00316 to APK, grant PI2100989 to RD, grant PI22/00428 to EFR); Red de Enfermedades Inflamatorias (RICORS RD21/0002/0034) from Instituto de Salud Carlos III and cofinanced by the European Regional Development Fund “A way to achieve Europe” (ERDF) and PRTR to APK; European Commission Horizon 2020 FP (Project VIRUSCAN FETPROACT-2016: ID 731868); Horizon Europe FP (Project EPIC-CROWN-2 ID: 101046084); and Fundación Caixa-Health Research (Project StopEbola HR18-00469) to RD. This research was also funded by the European Commission – NextGenerationEU (Regulation EU 2020/2094), through CSIC’s Global Health Platform (PTI Salud Global). MSF was funded by a Formación de Personal Investigador predoctoral fellowship from Ministerio de Ciencia e Innovación (grant PRE2018-083396). ERV was funded by a Rio-Hortega grant CM19/00149 from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and cofunded by the ERDF. SFDCO was funded by the PREDINMUN-COVID Grant (Fondo Supera COVID-19 from Banco de Santander and CRUE) and PDW by PI19/00096.Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Long-term thermal sensitivity of Earth’s tropical forests

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate

1er. Coloquio de educación para el diseño en la sociedad 5.0

Las memorias del 1er. Coloquio de Educación para el Diseño en la Sociedad 5.0 debenser entendidas como un esfuerzo colectivo de la comunidad de académicos de la División de Ciencias y Artes para el Diseño, que pone de manifiesto los retos y oportunidades que enfrenta la educación en diseño en un contexto de cambio acelerado y rompimiento de paradigmas.El evento se realizó el pasado mes de mayo de 2018 y se recibieron más de 50 ponencias por parte de las profesoras y profesores de la División.Las experiencias y/o propuestas innovadoras en cuanto a procesos de enseñanza y aprendizaje que presentan los autores en cada uno de sus textos son una invitación a reflexionar sobre nuestra situación actual en la materia, y emprender acciones en la División para continuar brindando una educación de calidad en diseño a nuestras alumnas, alumnos y la sociedad.Adicionalmente, se organizaron tres conferencias magistrales sobre la situación actual de la educación en Diseño y de las Instituciones de Educación Superior, impartidas por el Mtro. Luis Sarale, profesor de la Universidad Nacional de Cuyo en Mendoza (Argentina), y Presidente en su momento, de la Red de Carreras de Diseño en Universidades Públicas Latinoamericanas (DISUR), el Dr. Romualdo López Zárate, Rector de la Unidad Azcapotzalco, así como del Mtro. Luis Antonio Rivera Díaz, Jefe de Departamento de Teoría y Procesos del Diseño de la División de la Ciencias de la Comunicación y Diseño, en la Unidad Cuajimalpa de nuestra institución.La publicación de estas memorias son un esfuerzo divisional, organizado desde la Coordinación de Docencia Divisional y la Coordinación de Tecnologías del Aprendizaje, del Conocimiento y la Comunicación, para contribuir a los objetivos planteados en el documento ACCIONES:Agenda CyAD2021, en particular al eje de Innovación Educativa. Es necesario impulsar a todos los niveles de la División espacios de discusión orientados a reflexionar sobre el presente y futuro en la educación del diseñador, que contribuya a mejorar la calidad de la docencia y favorezca al fortalecimiento de los procesos de enseñanza y aprendizaje.Finalmente, extiendo un amplio reconocimiento a todos los miembros de la División que hicieron posible este evento, así como a todos los ponentes y participantes por compartir su conocimiento para que la División sea cada día mejor

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Experiencias de aprendizaje

Libro de experiencias de aprendizaje del grupo de investigación Giteca y de los semilleros de investigación en la que se visualizan las diferentes experiencias lideradas por instructores y aprendices en las diferentes áreas y líneas de formación.Book of learning experiences of the Giteca research group and the research hotbeds in which the different experiences led by instructors and apprentices in the different areas and lines of training are visualized.Propagación in vitro como un camino de aprendizaje para la formación profesional integral -- Experiencias significativas de aprendizaje, laboratorio de hematología y parasitología animal del Complejo Tecnológico para la Gestión Agroempresarial CTPGA-SENA -- Experiencias significativas adquiridas por aprendices en el área de SENNOVA, Complejo Tecnológico para la Gestión Agroempresarial. Regional – Antioquia -- El papel de la prensa escrita en el desarrollo de la competencia textual -- Aprendiendo a Emprender con un emprendedor -- Ven y te cuento sobre ADSI -- Observaciones fenológicas del cultivo de cacao (Theobroma cacao) en los municipios de Tarazá, El Bagre y Caucasia dentro de la formación del programa SENA emprende rural -- Tejiendo sueños desde la formación -- Forraje verde hidropónico como alternativa para disminuir la expansión de la frontera agrícola en el Putumayo -- La importancia del saber hacer para ser competente en el sector agrícola -- Experiencia significativa de aprendizaje semilleros de investigación -- La investigación como ente transformador de pensamientos -- Piscícola Paraguay; Mi Sueño, Mi Proyecto de Vida! -- Estrategia de aprendizaje a través de la investigación y la empresa aplicando un programa de Responsabilidad Social Empresarial –RSE -- Matemática aplicada para procesos agroindustriales de panificaciónna85 página

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks