RESUMEN
Mesenchymal stem cells (MSCs) possess unique paracrine and immunosuppressive properties, which make them useful candidates for cellular therapy. Here, we address how cellular senescence influences the therapeutic potential of human MSCs (hMSCs). Senescence was induced in bone marrow-derived hMSC cultures with gamma irradiation. Control and senescent cells were tested for their immunoregulatory activity in vitro and in vivo, and an extensive molecular characterization of the phenotypic changes induced by senescence was performed. We also compared the gene expression profiles of senescent hMSCs with a collection of hMSCs used in an ongoing clinical study of Graft Versus Host disease (GVHD). Our results show that senescence induces extensive phenotypic changes in hMSCs and abrogates their protective activity in a murine model of LPS-induced lethal endotoxemia. Although senescent hMSCs retain an ability to regulate the inflammatory response on macrophages in vitro, and, in part retain their capacity to significantly inhibit lymphocyte proliferation, they have a severely impaired migratory capacity in response to proinflammatory signals, which is associated with an inhibition of the AP-1 pathway. Additionally, expression analysis identified PLEC, C8orf48, TRPC4, and ZNF14, as differentially regulated genes in senescent hMSCs that were similarly regulated in those hMSCs which failed to produce a therapeutic effect in a GVHD trial. All the observed phenotypic alterations were confirmed in replicative-senescent hMSCs. In conclusion, this study highlights important changes in the immunomodulatory phenotype of senescent hMSCs and provides candidate gene signatures which may be useful to evaluate the therapeutic potential of hMSCs used in future clinical studies.
Asunto(s)
Senescencia Celular , Endotoxemia/terapia , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/fisiología , Animales , Movimiento Celular , Proliferación Celular , Células Cultivadas , Endotoxemia/inmunología , Humanos , Inmunomodulación , Lipopolisacáridos/farmacología , Linfocitos/inmunología , Masculino , Ratones Endogámicos BALB C , Plectina/genética , Plectina/metabolismo , Canales Catiónicos TRPC/genética , Canales Catiónicos TRPC/metabolismo , Factor de Transcripción AP-1/metabolismo , TranscriptomaRESUMEN
MicroRNAs, small noncoding RNAs, regulate gene expression primarily at the posttranscriptional level. We previously found that miR-335 is critically involved in the regulation and differentiation capacity of human mesenchymal stem cells (hMSCs) in vitro. In this study, we investigated the significance of miR-335 for the therapeutic potential of hMSCs. Analysis of hMSCs in ex vivo culture demonstrated a significant and progressive increase in miR-335 that is prevented by telomerase. Expression levels of miR-335 were also positively correlated with donor age of hMSCs, and were increased by stimuli that induce cell senescence, such as γ-irradiation and standard O2 concentration. Forced expression of miR-335 resulted in early senescence-like alterations in hMSCs, including: increased SA-ß-gal activity and cell size, reduced cell proliferation capacity, augmented levels of p16 protein, and the development of a senescence-associated secretory phenotype. Furthermore, overexpression of miR-335 abolished the in vivo chondro-osseous potential of hMSCs, and disabled their immunomodulatory capacity in a murine experimental model of lethal endotoxemia. These effects were accompanied by a severely reduced capacity for cell migration in response to proinflammatory signals and a marked reduction in Protein Kinase D1 phosphorylation, resulting in a pronounced decrease of AP-1 activity. Our results demonstrate that miR-335 plays a key role in the regulation of reparative activities of hMSCs and suggests that it might be considered a marker for the therapeutic potency of these cells in clinical applications.
Asunto(s)
Diferenciación Celular/genética , Senescencia Celular/genética , Células Madre Mesenquimatosas/fisiología , MicroARNs/genética , Factor de Transcripción AP-1/metabolismo , Western Blotting , Movimiento Celular/genética , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción GenéticaRESUMEN
Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of the CPC proteome associable with specific functions by comparison with human bone marrow mesenchymal stem cells (MSC), the reference population for cell therapy, and human dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially in CPC. iTRAQ analysis confirmed differential expression of a substantial proportion of those proteins in CPC relative to MSC, and systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment comprised 1,595 proteins, including a minimal signature of 167 proteins preferentially or exclusively expressed by CPC. CDH5 (VE-cadherin), OX2G (OX-2 membrane glycoprotein; CD200), GPR4 (G protein-coupled receptor 4), CACNG7 (calcium voltage-gated channel auxiliary subunit gamma 7) and F11R (F11 receptor; junctional adhesion molecule A; JAM-A; CD321) were selected for validation. Their differential expression was confirmed both in expanded CPC batches and in early stages of isolation, particularly when compared against cardiac fibroblasts. Among them, GPR4 demonstrated the highest discrimination capacity between all cell lineages analyzed.
Asunto(s)
Diferenciación Celular/fisiología , Corazón/crecimiento & desarrollo , Miocitos Cardíacos/metabolismo , Adulto , Antígenos CD , Biomarcadores , Cadherinas , Canales de Calcio , Moléculas de Adhesión Celular , Perfilación de la Expresión Génica/métodos , Humanos , Células Madre Mesenquimatosas/metabolismo , Células Madre Multipotentes/metabolismo , Proteoma/genética , Proteómica/métodos , Receptores de Superficie Celular , Receptores Acoplados a Proteínas G , Transcriptoma/genéticaRESUMEN
Resumen (analítico) El estudio aborda aspectos diferenciadores en la producción de medios escolares que trascienden la visión divulgativa y tradicional de estas experiencias. La indagación se adelantó en instituciones educativas del Valle de Aburrá (Antioquia) y Montería (Córdoba). Desde el punto de vista teórico, se asumen los medios escolares en el campo de la comunicación/educación. La investigación cualitativa se basó en testimonios y reflexiones de estudiantes consultados mediante grupos focales. Los resultados se estructuraron a partir de dos categorías emergentes: temas propios y atribución de sentido. El hallazgo principal indica que los medios escolares se constituyen en un espacio y un proceso que hacen posible la discusión, la deliberación y el establecimiento de acuerdos para la producción, construcción de significados y circulación de contenidos relacionados con el contexto de los estudiantes.
Abstract (analytical) This article examines the differentiating aspects in the production of school media, which transcend the informative and traditional vision of these experiences in educational institutions in Valle de Aburrá (Antioquia) and Montería (Córdoba). From a theoretical point of view, he topic of school media is addressed from the field of communication/education. The research is qualitative and based on the testimonies and reflections of students consulted through focus groups. The research results are structured using two emerging categories: own topics and attribution of meaning. The main finding indicates that school media constitute a space / process that facilitates discussion, deliberation and the establishment of agreements for media production, construction of meanings and circulation of content related to the contexts of students.
Resumo (analítico) São abordados os aspetos diferenciadores da produção da mídia escolar que transcendem a visão informativa e tradicional dessas experiências nas instituições de ensino do Vale de Aburrá (Antioquia) e Montería (Córdoba). Do ponto de vista teórico, as mídias escolares são assumidas a partir do campo da comunicação/educação. A pesquisa é qualitativa e está baseada nos depoimentos e reflexões dos alunos consultados por meio de grupos focais. Os resultados da pesquisa são estruturados a partir de duas categorias emergentes: temas próprios e atribuição de sentido. A principal constatação indica que as mídias escolares se constituem em um espaço e um processo que possibilita a discussão, deliberação e o estabelecimento de pactos para a produção, construção de significados e circulação de conteúdos relacionados ao contexto dos alunos.
RESUMEN
RESUMEN Fundamento: el sueño es reconocido como un indicador de calidad de vida y, en la vida cotidiana de un estudiante, adquiere gran relevancia por su relación con el funcionamiento cognitivo y las actividades académicas. Objetivo: identificar y evaluar los factores asociados a la calidad de sueño que presentan estudiantes chilenos de la carrera de Obstetricia, según años cursados. Métodos: estudio transversal y analítico realizado en el año lectivo 2018 en una universidad chilena, que incluyó la totalidad de estudiantes de la carrera de Obstetricia, quienes respondieron un cuestionario que evaluó los antecedentes sociodemográficos, el perfil académico, los hábitos previos al dormir y la calidad de sueño, evaluada mediante la encuesta de Pittsburg de calidad de sueño (Pittsburgh Sleep Quality Index, PSQI). Resultados: el comportamiento en torno a los hábitos del sueño difiere significativamente entre los cursos, en el 1° y el 4° año se encuentran quienes duermen menos y los estudiantes de este último curso son clasificados como los peores dormidores. El promedio de los componentes del PSQI varía entre 6, 6 (5° año) y 9,2 (4° año); el componente disfunción diurna mostró los valores más extremos. Conclusiones: existe una débil asociación entre la calidad de sueño y las variables sociodemográficas, perfil académico y hábitos previos al dormir. Solo se asocia fuertemente con algunos componentes de la encuesta de calidad de sueño, como la hora de acostarse y las horas de sueño del estudiante. La progresión de la carrera no supone un alza o disminución de los malos o buenos dormidores.
ABSTRACT Foundation: sleep is recognized as an indicator of quality of life and, in a student´s daily life, it acquires great importance for its relationship with cognitive functioning and academic activities. Objective: to identify and evaluate factors associated with quality of sleep presented by the Chilean students of the Obstetric training program, according to years studied. Methods: cross-sectional and analytical study conducted in the 2018 school year in a Chilean university, which included all the students of Obstetrics, who answered a questionnaire that evaluated sociodemographic background, academic profile, previous sleep habits and sleep quality, assessed by the Pittsburgh Sleep Quality Index (PSQI) survey. Results: the behavior around the sleep habits differs significantly among courses, in the 1st and 4th year there are those who sleep less and the students of this last course are classified as the worst sleepers. The average of the PSQI components varies between 6, 6 (5th year) and 9.2 (4th year); daytime dysfunction component showed the most extreme values. Conclusions: there is a weak association between sleeping quality and sociodemographic variables, academic profile and previous sleep habits. It is only strongly associated with some components of the sleep quality survey, such as bedtime and student sleeping hours. The training program progression does not mean an increase or decrease in bad or good sleepers.
RESUMEN
Resumen Las diferentes trayectorias criminales son el resultado de los cambios que se van produciendo en una persona a lo largo de toda su vida. Estas variaciones son observables a través de la forma que adquieren las curvas de la relación entre edad y delito. El objetivo de esta investigación es verificar cómo los cambios a través del desarrollo de la vida influyen en el cómo y cuándo se manifiesta el comportamiento criminal. Las trayectorias criminales fueron identificadas con base en la información delictual retrospectiva obtenida mediante entrevistas y autoinformes, en un grupo de 168 internos del Centro Penitenciario de Jóvenes de Cataluña, de entre 18 y 24 años. La curva general reproduce la forma tradicional de la relación entre edad y delito. Se identificaron ocho tipos diferentes de trayectorias, cada una de las cuales representa un tipo distinto de delincuente. Tales diferencias no solo involucran magnitud (cantidad de delitos), sino cómo estos delitos se presentan, o no, a través de diferentes momentos de la vida de las personas, confirmándose los postulados de la Criminología del Desarrollo y del Curso de la Vida.
Abstract The different criminal trajectories are the result of the changes that occur in a person throughout his life. These deviations are observable through the shape that curves have got with regard to age-crime relationship. The objective of this research is to verify in what way the changes through the life development impact on how and when the criminal behavior is revealed. The criminal trajectories were identified according to the retrospective tort information obtained by interviews and self-reports in a group of 168 prisoners between 18 and 24 years old at the Centro Penitenciario de Jóvenes de Cataluña (Penitentiary Center for Young People in Cataluña). The general curve reproduces the traditional way of the relationship between age and crime. Eight different types of trajectories were identified. Each trajectory represents a different type of criminal. These differences involve not only magnitude (amount of crimes), but also the mode these crimes are presented, or not, through the different moments of the people's lives, ratifying the tenets of Criminology and Development and the Life-Course.
Resumo As diferentes trajetórias criminais são o resultado das mudanças que se vão produzindo em uma pessoa ao longo da sua vida. Essas variações são observáveis por meio da forma que tomam as curvas da relação entre idade e delito. O objetivo de esta pesquisa é verificar como as mudanças no desenvolvimento da vida influem no como e quando se manifesta o comportamento criminal. As trajetórias criminais foram identificadas com base na informação delitiva retrospectiva obtida mediante entrevistas e autorelatórios, em um grupo de 168 internos do Centro Penitencial de Jovens da Catalunha, de entre 18 e 24 anos. A curva geral reproduz a forma tradicional da relação entre idade e delito. Identificaram-se oito tipos diferentes de trajetórias, cada uma das quais representa um tipo distinto de delinquente. Tais diferenças não só envolvem magnitude (quantidade de delitos), mas também como esses delitos se apresentam, ou não, por meio de diferentes momentos da vida das pessoas, confirmando-se os postulados da Criminologia do Desenvolvimento e do Curso da Vida.
Asunto(s)
Criminología , Prisiones , Criminales , ReincidenciaRESUMEN
ABSTRACT Objective: identify the factors associated with subjective wellbeing in older adults. Method: analytical, cross-sectional study developed in Chile. The sample consisted of 20,351 seniors, who answered a question on overall life satisfaction in the National Socio-Economic Survey, 2011. Subjective wellbeing was correlated with health, demographic and social indicators. Comparisons of averages, correlations and regressions were applied using the software Statistical Package for the Social Sciences 20. Results: life satisfaction was associated with increased age; being male; participation in social organizations; being married or living as a couple; having higher education level; higher income; good perceived health status and better health care. Conclusion: according to the age and income predictors, it can be concluded that, over the years, life satisfaction is reinforced, but in combination with adequate perceived health and income, which permit an excellent quality of life.
RESUMO Objetivo: identificar os fatores associados ao bem-estar subjetivos dos idosos. Método: estudo analítico, transversal, realizado no Chile. A amostra correspondeu a 20.351 idosos que responderam a uma pergunta sobre satisfação vital global no Inquérito de Caracterização Socioeconômica Nacional, 2011. O indicador de bem-estar subjetivo foi correlacionado com indicadores de saúde, demográficos e sociais. Foram comparadas médias e análise de correlação e regressão com o programa Statistical Package for the Social Sciences 20. Resultados: a satisfação com a vida associou-se com maior idade; ser homem; participação em organizações sociais; ser casado ou viver junto; ter estudos superiores; maior renda; boa percepção do estado de saúde e maior atenção sanitária. Conclus ão: ao observar os preditores idade e renda pode-se concluir que o passar dos anos reforça a satisfação com a vida, mas em confluência com uma adequada percepção de saúde e renda que permitam uma qualidade de vida ótima.
RESUMEN Objetivo: identificar los factores asociados al bienestar subjetivo en los adultos mayores. Método: estudio analítico, transversal desarrollado en Chile. La muestra correspondió a 20.351 adultos mayores, que respondieron una pregunta sobre satisfacción vital global en la Encuesta de Caracterización Socioeconómica Nacional, 2011. El bienestar subjetivo fue correlacionado con indicadores de salud, demográficos y sociales. Se aplicaron comparaciones de medias, correlaciones y regresiones, mediante el programa Statistical Package for the Social Sciences 20. Resultados: la satisfacción con la vida se asoció con mayor edad; ser hombre; participación en organizaciones sociales; estar casado o convivir en pareja; tener estudios superiores; mayor ingreso; buena percepción del estado de salud; mejor atención sanitaria. Conclusión: al observar los predictores edad e ingresos, se puede concluir que el paso de los años refuerza la satisfacción con la vida pero, en confluencia con una adecuada percepción de salud e ingresos, que permitan una calidad de vida óptima.
Asunto(s)
Humanos , Anciano , Satisfacción Personal , Calidad de Vida , Anciano , Salud del Anciano , Enfermería , Determinantes Sociales de la Salud , FelicidadRESUMEN
Este trabajo analiza las propiedades psicométricas de la escala BMSLSS de Seligson, Huebner y Valois (2003) en niños y niñas chilenos. Se aplicó a 1096 estudiantes de 10, 11 y 12 años. Se realizaron análisis de confiabilidad, análisis factorial exploratorio (EFA) y confirmatorio (CFA) y correlación ítem con puntaje total. Los resultados exhiben una aceptable confiabilidad interna de la escala (a = 0.7), un solo factor en la estructura factorial de la escala y adecuada correlación ítem con puntaje total (entre 0.55 y 0.73). El estudio fundamenta el uso de BMSLSS en Chile en población infantil y aporta herramientas de medición de indicadores sociales para la infancia en países en vías de desarrollo de habla hispana.
This paper analyzes the psychometric properties of the Brief Multidimensional Students' Life Satisfaction Scale -BMSLSS (Seligson, Huebner and Valois, 2003) in Chilean children. 1096 Chilean students of 10, 11 and 12 years-old participated in the study. Reliability analysis, exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and item correlation with total score were performed. Results show acceptable internal reliability of the scale (a = 0.7), a single factor structure of the scale and appropriate item correlation with total score (between 0.55 and 0.73) This study supports the use of the BMSLSS in children in Chile in the school context, and also provides measurement tools for social indicators for children in Spanish-speaking developing countries.