TAZ Controls Helicobacter pylori-Induced Epithelial–Mesenchymal Transition and Cancer Stem Cell-Like Invasive and Tumorigenic Properties

Helicobacter pylori infection, the main risk factor for gastric cancer (GC), leads to an epithelial–mesenchymal transition (EMT) of gastric epithelium contributing to gastric cancer stem cell (CSC) emergence. The Hippo pathway e ectors yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) control cancer initiation and progression in many cancers including GC. Here, we investigated the role of TAZ in the early steps of H. pylori-mediated gastric carcinogenesis. TAZ implication in EMT, invasion, and CSC-related tumorigenic properties were evaluated in three gastric epithelial cell lines infected by H. pylori. We showed that H. pylori infection increased TAZ nuclear expression and transcriptional enhancer TEA domain (TEAD) transcription factors transcriptional activity. Nuclear TAZ and zinc finger E-box-binding homeobox 1 (ZEB1) were co-overexpressed in cells harboring a mesenchymal phenotype in vitro, and in areas of regenerative hyperplasia in gastric mucosa of H. pylori-infected patients and experimentally infected mice, as well as at the invasive front of gastric carcinoma. TAZsilencing reduced ZEB1 expression andEMTphenotype, and strongly inhibited invasion and tumorsphere formation induced by H. pylori. In conclusion, TAZ activation in response to H. pylori infection contributes to H. pylori-induced EMT, invasion, and CSC-like tumorigenic properties. TAZ overexpression in H. pylori-induced pre-neoplastic lesions and in GC could therefore constitute a biomarker of early transformation in gastric carcinogenesis.Ligue Nationale Française Contre le Cancer (French National League against Cancer)/[]//FranciaUniversidad de Costa Rica/[]/UCR/Costa RicaMinisterio de Ciencia, Innovación, Tecnología y Telecomunicaciones/[]/MICITT/Costa RicaFrench National Cancer Institute/[PLBio 2014-152]/INCa/FranciaLigue Contre le Cancer/[]//FranciaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Leukaemia Inhibitory Factor (LIF) inhibits cancer stem cells tumorigenic properties through hippo kinases activation in gastric cancer

Cancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF’s effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF’s treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs’ response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF’s anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.Ministry of Tertiary Education, Research and Innovation/[]//FranciaLigue Nationale Française Contre le Cancer (French National League against Cancer)/[]//FranciaUniversidad de Costa Rica/[]/UCR/Costa RicaMinisterio de Ciencia, Innovación, Tecnología y Telecomunicaciones/[]/MICITT/Costa RicaFrench National Cancer Institute/[PLBio 2014-152]/INCa/FranciaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Amongst tests and masks: Perception about the restart of digestive endoscopy during COVID-19

COVID-19 ha generado una pausa en la endoscopia electiva, retrasando el diagnóstico de múltiples patologías. Existen varias propuestas para reiniciar las actividades que incluyen el tamizaje por COVID-19 y un reinicio escalonado.Introducción: COVID-19 ha generado una pausa en la endoscopia electiva, retrasando el diagnóstico de múltiples patologías. Existen varias propuestas para reiniciar las actividades que incluyen el tamizaje por COVID-19 y un reinicio escalonado. Objetivo: Conocer la percepción general de los endoscopistas respecto al reinicio de procedimientos electivos, y la influencia que genera la disponibilidad de equipo de protección personal (EPP) y tamizaje. Metodología: Se encuestan endoscopistas expertos con preguntas enfocadas a la endoscopia durante la pandemia, así como de disponibilidad de EPP y del uso de pruebas de tamizaje de SARS-CoV-2. La encuesta fue distribuida vía e-mail, mensajería instantánea y por contacto directo a distintas sociedades de endoscopia, obteniendo respuesta completa de 168 médicos. Resultados: 88% de los encuestados no practican tamizaje por COVID-19 sin embargo un 70% considera apropiada esta práctica. El 80% afirma contar con EPP adecuado. El 94% de los médicos afirma que deben reiniciarse los procedimientos lo antes posible. Conclusiones: Los endoscopistas latinoamericanos con mayor disponibilidad de EPP, así como la implementación de tamizaje de SARS-CoV-2, presentaron mayor disposición a reiniciar las endoscopias electivas.Introduction: COVID-19 has paused elective procedures and delayed the diagnosis of multiple pathologies. Different proposals have been recommended for restarting elective procedures, including screening tests and a gradual restart. ­ Objective: To know the perception of Latin American endoscopists regarding the restart of elective procedures, and how the availability of personal protection equipment (PPE) and prior testing may influence this perception. Methods: A web-based survey was developed by endoscopy experts, based in the development of endoscopy, availability of PPE and screening tests, which was distributed via e-mail, social media and direct contact by one author to several societies. Full response was obtained from 168 endoscopists during May 2020. Results: 88% of surveyed endoscopists don’t screen for COVID-19 prior to endoscopy, however, 70% consider this appropriate. 80% affirm having PPE. 94% believe that endoscopic practice must be restarted as soon as possible. Conclusions: Latin American endoscopists with greater amount of PPE and prior testing for SARS-CoV-2 were more willing to restart elective procedures than those in limited scenarios.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA)UCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de NutriciónUCR::Vicerrectoría de Docencia::Salud::Facultad de Medicina::Escuela de Medicin

The Hippo Kinase LATS2 Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Intestinal Metaplasia in Gastric Mucosa

Gastric carcinoma is related mostly to CagA+-Helicobacter pylori infection, which disrupts the gastric mucosa turnover and elicits an epithelial-mesenchymal transition (EMT) and preneoplastic transdifferentiation. The tumor suppressor Hippo pathway controls stem cell homeostasis; its core, constituted by the large tumor suppressor 2 (LATS2) kinase and its substrate Yes-associated protein 1 (YAP1), was investigated in this context.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Evaluación por pares y heteroevaluación en un proyecto de creación de materiales para la divulgación científica enfermera

[EN] Peer evaluation is an evaluation strategy that allows meaningful learning. In this experience, a project for the creation of informative material has been proposed, evaluated by peers through a rubric and with quantitative and qualitative return of the assessment to the creators of the material. Once the subject creation project was completed, an evaluation was carried out by teaching staff outside the project in order to verify the coherence of both evaluations. The results have shown that the students carry out a more benevolent evaluation than the teachers, but both controls were coherent in the continuous evaluation of learning. We can say that the use of the rubric as a peer assessment tool is useful and brings benefits to learning, but it is necessary to identify a criterion that allows resolving the differences observed in the results issued by students and teachers.[ES] La evaluación por pares es una estrategia de evaluación que permite un aprendizaje significativo. En esta experiencia se ha planteado un proyecto de creación de material divulgativo, evaluado por pares mediante una rúbrica y con devolución cuantitativa y cualitativa de la valoración a los creadores del material. Finalizado el proyecto de creación de materia, se realizó una evaluación por personal docente ajeno al proyecto con la finalidad de comprobar la coherencia de ambas evaluaciones. Los resultados han mostrado que el alumnado realiza una evaluación más benevolente que los docentes, pero ambos controles fueron coherentes en la evaluación continua del aprendizaje. Podemos decir que el uso de la rúbrica como herramienta de evaluación entre iguales es útil y aporta beneficios al aprendizaje, pero es necesario identificar un criterio que permita resolver las diferencias observadas en los resultados emitidos por estudiantes y docentes.García-Martínez, P.; García Molina, P.; Ruiz Oliva, E.; Buck Sainz-Rocas, P.; González Blazquez, F.; Trujillo Barberá, S.; Castro Calvo, J.... (2023). Evaluación por pares y heteroevaluación en un proyecto de creación de materiales para la divulgación científica enfermera. Editorial Universitat Politècnica de València. 367-375. https://doi.org/10.4995/INRED2023.2023.1655536737

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). Conclusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup

The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). Conclusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup

Multi-ancestry GWAS reveals excitotoxicity associated with outcome after ischaemic stroke

During the first hours after stroke onset, neurological deficits can be highly unstable: some patients rapidly improve, while others deteriorate. This early neurological instability has a major impact on long-term outcome. Here, we aimed to determine the genetic architecture of early neurological instability measured by the difference between the National Institutes of Health Stroke Scale (NIHSS) within 6 h of stroke onset and NIHSS at 24 h. A total of 5876 individuals from seven countries (Spain, Finland, Poland, USA, Costa Rica, Mexico and Korea) were studied using a multi-ancestry meta-analyses. We found that 8.7% of NIHSS at 24 h of variance was explained by common genetic variations, and also that early neurological instability has a different genetic architecture from that of stroke risk. Eight loci (1p21.1, 1q42.2, 2p25.1, 2q31.2, 2q33.3, 5q33.2, 7p21.2 and 13q31.1) were genome-wide significant and explained 1.8% of the variability suggesting that additional variants influence early change in neurological deficits. We used functional genomics and bioinformatic annotation to identify the genes driving the association from each locus. Expression quantitative trait loci mapping and summary data-based Mendelian randomization indicate that ADAM23 (log Bayes factor = 5.41) was driving the association for 2q33.3. Gene-based analyses suggested that GRIA1 (log Bayes factor = 5.19), which is predominantly expressed in the brain, is the gene driving the association for the 5q33.2 locus. These analyses also nominated GNPAT (log Bayes factor = 7.64) ABCB5 (log Bayes factor = 5.97) for the 1p21.1 and 7p21.1 loci. Human brain single-nuclei RNA-sequencing indicates that the gene expression of ADAM23 and GRIA1 is enriched in neurons. ADAM23, a presynaptic protein and GRIA1, a protein subunit of the AMPA receptor, are part of a synaptic protein complex that modulates neuronal excitability. These data provide the first genetic evidence in humans that excitotoxicity may contribute to early neurological instability after acute ischaemic stroke. Ibanez et al. perform a multi-ancestry meta-analysis to investigate the genetic architecture of early stroke outcomes. Two of the eight genome-wide significant loci identified-ADAM23 and GRIA1-are involved in synaptic excitability, suggesting that excitotoxicity contributes to neurological instability after ischaemic stroke.Peer reviewe

Famílies botàniques de plantes medicinals

Facultat de Farmàcia, Universitat de Barcelona. Ensenyament: Grau de Farmàcia, Assignatura: Botànica Farmacèutica, Curs: 2013-2014, Coordinadors: Joan Simon, Cèsar Blanché i Maria Bosch.Els materials que aquí es presenten són els recull de 175 treballs d’una família botànica d’interès medicinal realitzats de manera individual. Els treballs han estat realitzat per la totalitat dels estudiants dels grups M-2 i M-3 de l’assignatura Botànica Farmacèutica durant els mesos d’abril i maig del curs 2013-14. Tots els treballs s’han dut a terme a través de la plataforma de GoogleDocs i han estat tutoritzats pel professor de l’assignatura i revisats i finalment co-avaluats entre els propis estudiants. L’objectiu principal de l’activitat ha estat fomentar l’aprenentatge autònom i col·laboratiu en Botànica farmacèutica

La gestión académica en pandemia : adecuaciones, innovaciones y desafíos de la Universidad Nacional de Cuyo

Este libro remite a un contexto especial e inédito que surge a partir de la pandemia de covid-19. Se trata de un contexto de alcance global signado por efectos intensos y perdurables sobre diferentes aspectos de la realidad social, económica y ambiental. En general, estos efectos provocaron, por un lado, situaciones problemáticas nuevas y, por otro lado, agravaron situaciones problemáticas preexistentes que adquirieron mayor visibilidad. En el caso argentino, las restricciones derivadas de la pandemia agudizaron la brecha socioeducativa existente y, al mismo tiempo, exigieron una gestión ágil, dinámica, resolutiva, propositiva y resiliente, especialmente a las instituciones educativas con el objeto de asegurar el derecho a la educación y su calidad. Lógicamente, la provincia de Mendoza y, por tanto, la Universidad Nacional de Cuyo (UNCUYO) no quedaron exentas de los efectos mencionados. Aunque aún no resulta posible identificar con rigor el impacto concreto que ha tenido la pandemia sobre el funcionamiento del sistema educativo provincial, se pueden entrever algunos indicadores que vale la pena atender. Por ejemplo, el egreso en la oferta de educación superior de la uncuyo registró, en 2020, una caída interanual cercana al -18 % 1. Esta oscilación se torna más relevante si se considera que este indicador se mostraba estable a lo largo de los últimos años.Fil: Castañeda, Linda. Universidad de Murcia.Fil: Viñoles Cosentino, Virginia. Universidad de Murcia.Fil: Falcón, Paulo.Fil: Martínez, Ana María.Fil: Meljin Lombard, Mariela Beatriz. Universidad Nacional de Cuyo. Facultad de Artes y Diseño.Fil: Van Den Bosch, Silvia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias.Fil: Castro, María Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria.Fil: Puebla, Patricia. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Sánchez, Esther Lucía. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: González Gaviola, Miguel. Universidad Nacional de Cuyo. Facultad de Ciencias Económicas.Fil: Tarabelli, María Florencia. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales.Fil: Rüttler, María Elena. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Nalda, Gonzalo. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas.Fil: Castiglia, Mariana. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales.Fil: Mussuto, Matías M.. Universidad Nacional de Cuyo. Facultad de Derecho.Fil: Griffouliere, María Gabriela. Universidad Nacional de Cuyo. Facultad de Educación.Fil: Verstraete, María Ana. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras.Fil: Echagaray, Patricia. Universidad Nacional de Cuyo. Facultad de Odontología.Fil: Mirasso, Aníbal. Universidad Nacional de Cuyo. Facultad de Ingeniería.Fil: Molina, Fabiana. Universidad Nacional de Cuyo. Instituto Tecnológico Universitario.Fil: Corral, Patricia. Universidad Nacional de Cuyo. Instituto Universitario de Seguridad Pública.Fil: Chrabalowski, Marina. Universidad Nacional de Cuyo.Fil: Barrozo, María Ana. Universidad Nacional de Cuyo.Fil: Zabala, Cecilia. Universidad Nacional de Cuyo. Escuela de Comercio Martín Zapata.Fil: Sauer, Marcelo. Universidad Nacional de Cuyo.Fil: Romero Day, Marcela. Universidad Nacional de Cuyo. Liceo Agrícola y Enológico Domingo F. Sarmiento.Fil: Marlia, Nora. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras. Departamento de Aplicación Docente.Fil: Zamorano, Cristina. Universidad Nacional de Cuyo. Colegio Universitario Central.Fil: Yapura, Susana. Universidad Nacional de Cuyo. Escuela del Magisterio.Fil: Navarro, María Fernanda. Universidad Nacional de Cuyo.Fil: Bosio, Iris Viviana. Universidad Nacional de Cuyo. EDIUNC.Fil: Degiorgi, Horacio. Universidad Nacional de Cuyo. Sistema Integrado de Documentación.Fil: Bocco, María Susana. Universidad Nacional de Cuyo.Fil: Guayco, Mariana. Universidad Nacional de Cuyo.Fil: Pizzi, Daniel. Universidad Nacional de Cuyo.Fil: Lettelier, Dolores. Universidad Nacional de Cuyo. Secretaría Académica