Objetivo: analizar algunos predictores de la calidad de vida en personas mayores, diferenciando entre mayores jóvenes o muy mayores. Esto es, se estudia un potencial efecto moderador debido a ser muy ...mayor, dado que este sector de la población está en rápido crecimiento en todo el mundo. Materiales y métodos: estudio transversal analítico de encuesta a 224 personas mayores, en dos grupos diferenciales, menores de 75 años y 75 años o más, que viven en la ciudad de Valencia (España). Resultados: se ajustó un modelo estructural multimuestra donde las dimensiones de espiritualidad y la esperanza predicen dos indicadores de calidad de vida en personas mayores: satisfacción vital y percepción de salud. Se han encontrado relaciones estadísticamente significativas (p < 0,05) entre la espiritualidad y la esperanza, y los dos indicadores; especialmente potente es la predicción de la satisfacción vital. Asimismo, los resultados multimuestra indican que la fe juega un papel diferencial relevante en los muy mayores. Discusión: se ponen en relación los hallazgos con la literatura. Conclusiones: existe un importante impacto, en algunos casos diferencial para los muy mayores, de la espiritualidad sobre indicadores de envejecimiento con éxito tales como la satisfacción vital y la salud, y la capacidad para realizar actividades, ya sea instrumentales de la vida diaria, o en general todo tipo de actividades productivas.
Chemoresistance constitute nowadays the major contributor to therapy failure in most cancers. There are main factors that mitigate cell response to therapy, such as target organ, inherent sensitivity ...to the administered compound, its metabolism, drug efflux and influx or alterations on specific cellular targets, among others. We now know that intrinsic properties of cancer cells, including metabolic features, substantially contribute to chemoresistance. In fact, during the last years, numerous reports indicate that cancer cells resistant to chemotherapy demonstrate significant alterations in mitochondrial metabolism, membrane polarization and mass. Metabolic activity and expression of several mitochondrial proteins are modulated under treatment to cope with stress, making these organelles central players in the development of resistance to therapies. Here, we review the role of mitochondria in chemoresistant cells in terms of metabolic rewiring and function of key mitochondria-related proteins.
The proportion of elderly people is growing faster than any other age group. Amongst them, the group of oldest old is indeed the segment of the elderly population with the fastest growth rate. The ...increase in the proportion of elderly in the Angolan population makes research on this area badly needed. Within the theoretical framework of successful aging, the study aims to test for sociodemographic group differences in perceived health, life satisfaction, and social relations in Angolan elderly. The dependent variables are three of the components of what has been called successful aging. Data came from a cross-sectional survey of elderly people living in Luanda. 1003 Angolan elderly were surveyed on sociodemographic information, perceived health, life satisfaction, and social support. MANOVAs were calculated to test for mean differences in the dependent variables. Results permit to conclude that the factors associated with the largest differences on the Angolan elderly’s quality of life and social relations were age (becoming oldest old) and institutionalization. The interactions of several factors with age pointed out that the oldest old were clearly a group in which the decreased quality of life due to becoming oldest old could not be compensated by other factors, as it was the case in the group of young old.
Introducción: Uno de los elementos abordados desde la Estrategia para la Nutrición, Actividad física y prevención de la Obesidad y Salud (NAOS) es la alimentación en el medio escolar. Objetivo: ...Evaluar, tomando como referencia el conjunto mínimo de indicadores y recomendaciones de la Estrategia NAOS, una muestra de menús distribuidos en varios comedores escolares de Bizkaia. Métodos: Estudio descriptivo transversal basado en la revisión teórica de los menús basales distribuidos por siete cocinas centrales que abastecen a 324 centros escolares (80.969 alumnos). Se determinó y valoró la frecuencia semanal de varios grupos de alimentos; los documentos de referencia fueron "Evaluación y Seguimiento de la Estrategia NAOS: Conjunto de Indicadores" y las recomendaciones del "Documento de Consenso sobre la alimentación en los centros educativos". Resultados y discusión: El 100% de los comedores cumple con los mínimos relativos a legumbres, pescados y precocinados y con las recomendaciones relativas a carne y productos cárnicos. Si bien se aproximan bastante, ninguno cumple con los mínimos de fruta, verdura o con la información nutricional complementaria. Se han evidenciado diferencias entre las recomendaciones de La Estrategia NAOS y las condiciones exigidas por el Departamento de Educación, así como dificultades en la cuantificación y clasificación de varios alimentos. Conclusiones: Se recomienda incrementar el contenido en frutas, verduras, huevos y pescado azul de los menús escolares, así como ofrecer a las familias una información de los menús más detallada.
The anti-diabetic drug metformin targets pancreatic cancer stem cells (CSCs), but not their differentiated progenies (non-CSCs), which may be related to distinct metabolic phenotypes. Here we ...conclusively demonstrate that while non-CSCs were highly glycolytic, CSCs were dependent on oxidative metabolism (OXPHOS) with very limited metabolic plasticity. Thus, mitochondrial inhibition, e.g., by metformin, translated into energy crisis and apoptosis. However, resistant CSC clones eventually emerged during treatment with metformin due to their intermediate glycolytic/respiratory phenotype. Mechanistically, suppression of MYC and subsequent increase of PGC-1α were identified as key determinants for the OXPHOS dependency of CSCs, which was abolished in resistant CSC clones. Intriguingly, no resistance was observed for the mitochondrial ROS inducer menadione and resistance could also be prevented/reversed for metformin by genetic/pharmacological inhibition of MYC. Thus, the specific metabolic features of pancreatic CSCs are amendable to therapeutic intervention and could provide the basis for developing more effective therapies to combat this lethal cancer.
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•Pancreatic CSCs rely on mitochondrial OXPHOS and show reduced metabolic plasticity•Mitochondrial inhibition effectively eliminates pancreatic CSC•MYC/PGC-1α balance controls the metabolic phenotype of PDAC cells•MYC targeting prevents resistance/restores the response to metformin in resistant CSCs
Sancho et al. show that pancreatic cancer stem cells (CSCs) are especially vulnerable to mitochondrial-targeted therapies (i.e., metformin) due to their strong reliance on oxidative metabolism. The MYC/PGC-1α balance acts as the main determinant for this OXPHOS dependency, and genetic/pharmacological targeting of MYC restores metformin response in resistant CSCs.
Los enfoques de ensenanza a los que recurren los docentes universitarios determinan su forma de afrontar el proceso educativo y su figura como docentes. Estos pueden ser de dos tipos, centrado en el ...profesorado/transmision de la informacion y centrado en el alumnado/cambio conceptual. El objetivo de esta investigacion es dibujar el perfil del profesor universitario segun el enfoque docente mas empleado. Con este fin, se aplico el cuestionario ATI (2004) a un total de 501 docentes universitarios de la Region de Murcia. Los resultados muestran que el enfoque centrado en el alumnado es el mas empleado entre las profesoras que han recibido formacion didactica, de menor edad o anos de experiencia, preferiblemente de la rama de arte o humanidades y ciencias sociales y juridicas y dependiendo del tipo de universidad a la que pertenece. De este modo, es posible detectar las variables que determinan el uso de este enfoque, en detrimento del anterior, y como consecuencia, las areas donde es mas necesario trabajar para hacer posible el cambio.
En la actualidad, los nuevos requerimientos del siglo XXI en la formación docente son evidentes. El presente trabajo tiene como principal objetivo describir el perfil de los estudiantes ...universitarios en temas relevantes para su futuro profesional. Entre ellos se consideran importantes los enfoques de enseñanza, la atención a la diversidad, las TIC y su relación con el cyberbullying, la inteligencia emocional y la autoestima. La investigación fue llevada a cabo en la Universidad Católica de San Antonio de Murcia (UCAM) con una muestra de 230 estudiantes de Educación. Los instrumentos utilizados para este propósito fueron el cuestionario de autoestima Rosenberg, ATI, TMMS-24 y un instrumento diseñado ad-hoc para la atención a la diversidad y el uso de las TIC y su relación con el cyberbullying. Los resultados muestran un perfil definido de estudiantes mujeres, con una alta inteligencia emocional, autoestima dentro del promedio, que no favorecen un enfoque de enseñanza específico y con medios muy elevados en la atención a la diversidad y el cyberbullying.
1 INSERM, U872, Mort Cellulaire Programmée et Physiopathologie des Cellules Tumorales, Equipe 19, Centre de Recherche des Cordeliers, Paris, France
2 Université Pierre et Marie Curie-Paris 6, UMRS ...872, Paris, France
3 Université Paris Descartes, UMRS 872, Paris, France
4 Institut Pasteur, Paris, France
5 AP-HP, Groupe Hospitalier Pitie-Salpêtrière, Service d'Hématologie Biologique, Paris, France
6 Centre de Recherche du CHUM, Hôpital Notre-Dame, Laboratoire dImmunorégulation, Montréal, Canada
7 Cell Neurobiology Unit, Departament de Medicina Experimental, Universitat de Lleida, IRBLLEIDA, Lleida, Spain
Correspondence: Santos A. Susin. Centre de Recherche des Cordeliers. 15, rue de lEcole de Médecine, 75006, Paris, France. E-mail: santos.susin{at}crc.jussieu.fr
Background: Programmed cell death has been traditionally related with caspase activation. However, it is now accepted that caspase-independent forms of programmed cell death also regulate cell death. In chronic lymphocytic leukemia, CD47 ligation induces one of these alternative forms of cell death: type III programmed cell death. This poorly understood process is characterized by cytoplasmic hallmarks, such as mitochondrial damage. To gain insights into the molecular pathways regulating type III programmed cell death in chronic lymphocytic leukemia, we performed extensive biochemical and cell biology assessments.
Design and Methods: After CD47 triggering, purified B-cells from 20 patients with chronic lymphocytic leukemia were studied by flow cytometry, immunofluorescence and three-dimensional imaging, immunoblotting, electron microscopy, and fibrillar/globular actin measurements. Finally, we subjected CD47-treated chronic lymphocytic leukemia cells to a phagocytosis assay.
Results: We first confirmed that induction of type III programmed cell death is an efficient means of triggering cell death in chronic lymphocytic leukemia. Further, we demonstrated that the signaling events induced by CD47 ligation provoked a reduction in cell size. This alteration is related to F-actin disruption, as the two other cytoskeleton networks, microtubules and intermediate filaments, remain undisturbed in type III programmed cell death. Strikingly, we revealed that the pharmacological modulation of F-actin dynamics regulated this type of death. Finally, our data delineated a new programmed cell death pathway in chronic lymphocytic leukemia initiated by CD47 triggering, and followed by serine protease activation, F-actin rearrangement, mitochondrial damage, phosphatidylserine exposure, and cell clearance.
Conclusions: Our work reveals a key molecular tool in the modulation of cell death in chronic lymphocytic leukemia: F-actin. By assessing the regulation of F-actin and type III programmed cell death, this analysis provides new options for destroying chronic lymphocytic leukemia cells, such as a combination of therapies based on apoptosis regulators (e.g., caspases, Bcl-2, Bax) along with alternative therapies based on type III death effectors (e.g., F-actin).
Key words: actin, apoptosis, caspase-independent cell death, CD47, chronic lymphocytic leukemia, mitochondria.
FaO rat hepatoma cells show increased levels of the epidermal growth factor receptor (EGFR) ligands, when compared with adult normal hepatocytes, and higher activity of the TNF-alpha converting ...enzyme (TACE/ADAM17), which is required for EGFR ligand proteolysis and activation. In this work we have analysed the consequences of inhibiting the EGFR in FaO rat hepatoma cells, focusing the attention on autocrine growth and protection from apoptosis. Results have indicated that FaO cells show overactivation of the EGFR pathway, which induces basal growth (in the absence of serum) and protection from pro-apoptotic agents, such as doxorubicin, generating drug resistance. Treatment of cells with the combination of doxorubicin and the tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478, a potent and specific inhibitor of EGFR tyrosine kinase) potently inhibits autocrine growth and induces apoptosis. The apoptotic effect correlates with high expression and activation of the pro-apoptotic Bax and decreased transcript and protein levels of the anti-apoptotic Mcl-1 and Bcl-x
L. Furthermore, the combination of AG1478 and doxorubicin induces reactive oxygen species (ROS) production and glutathione depletion in FaO cells, coincident with up-regulation of the NADPH oxidase NOX4 and down-regulation of the gamma-glutamylcysteine synthetase (γ-GCS), a key regulatory enzyme of the glutathione synthesis. Incubation of cells with glutathione ethyl ester attenuates the apoptosis induced by the combination of doxorubicin and AG1478, which indicates that glutathione depletion is required for an efficient cell death. In conclusion, targeting EGFR combined with other conventional pro-apoptotic drugs should potentially be effective in antineoplastic therapy towards liver cancer.
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