Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)

Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discusse

Instrumento de Investigación para el análisis de las imágenes en la programación infantil de la Televisión

El  propósito  de  esta  investigación  ha  sido  acercarse  de  una  forma  diferente  al  estudio  de   las   imágenes   que   visionan   los   niños   y   niñas   en   los   documentos   audiovisuales   que   consumen   habitualmente.   Consideramos   que   éstas   son   de   suma   importancia   en   la   conformación   de   su   universo   gráfico.   Así   como   del   efecto   que   pueden   tener   en   su   educación   y   por   tanto   de   la   forma   de   entender   el   mundo   que   les   rodea   inundado   de   información   visual.   Presentamos   un   estudio   de   la   imagen   atendiendo   a   sus   valores   plásticos  como  objeto  de   análisis,   ya  que   los  consideramos   ingredientes  básicos  para  el   desarrollo  del  pensamiento  y  la  comunicación  visual.  Para  ello,  hemos  llevado  a  cabo  la   definición   y  perfeccionamiento  del  diseño  de   nuestra  plantilla  de  análisis,  poniéndola  a   prueba  mediante  la  validación  por  juicio  de  expertos  lo  cual  nos  ha  permitido  testear  su   fiabilidad  y  utilidad  para  un  estudio  futuro.  Hemos  conseguido  por  lo  tanto  contrastar  la   validez  de   la   versión  2.0  de   nuestra  plantilla  para  análisis  cuantitativo  de   imágenes   y   presentamos  aquí   un   instrumento  de  observación  para  acercarnos  a  conocer  qué   ven   los   niños  y  niñas  en  los  medios  audiovisuales  actuales  y  cuáles  son  las  características  de  las   imágenes  que  manejan.The   purpose   of   this   research   was   to   approach   differently   the   study   of   images   that   children   envision   in   the   audiovisual   documents   they   usually   watch.   Considering   the   importance   of   these   images   in   shaping   their   graphic   universe   and   the   effect   they   can   have  on  their  education  and  way  of   understanding  the  world  around   them,   now   flooded   with   visual   information.   We   have   presented   a   study   of   the   image   as   the   object   of   analysis   itself   paying   attention   to   its   plastic   values,   that   we   consider   basic   ingredients   for   the   development   of   thinking   and   visual   communication.   So   we've   carried   out   the   definition   and   refinement   of   the   design   of   our   analysis   template   by   testing   it   through   validation  by  expert   opinion,  which   has  allowed   us  to   test   its  reliability  and   usefulness   for  our   future  study.  Therefore,  we   have   managed  to   test   the   validity  of  the  2.0   version   of  our  Template  for  quantitative  image  analysis  and  we  present  here  an  observation  tool   to   get   closer   to   knowing   what   children   watch   in   today's   media   and   what   the   characteristics  of  the  images  they  handle  are

Propuesta de un ciclo de vida para creación y gestión del conocimiento. Actualización del análisis de las funcionalidades de las aplicaciones informáticas para la gestión de conocimiento

New paradigms for generation, capture, assimilation and knowledge transfer are stimulating the development of new methodologies and techniques. This in turn gives rise to a need to improve lifecycle processes for creating and managing knowledge. Current IT technologies allow the development of highly complex infrastructures for knowledge management, but it is socialand economic pressure that drives the development of specific applications in this field. Currently there are a large number of commercial knowledge management system for specific application areas, but no common platform that integrates these. Hopefully, in the not too distant future, we will have applications which better support global knowledge management for educational communities. Los nuevos paradigmas en cuanto a la generación, captura, asimilación, y transferencia del conocimiento como valor estratégico, están provocando el desarrollo de nuevas metodologías y técnicas con las que afrontarlos. En este sentido interesa que los Ciclos de Vida como procesos para la Creación y Gestión de Conocimiento se perfeccionen. El estado actual de las TIC posibilita el desarrollo de infraestructuras muy complejas que sirven de base para la GC, pero es sin duda la gran presión social y económica la que actúa de impulsora de la construcción de aplicaciones específicas de este campo. El escenario actual refleja la existencia de gran cantidad de SGC comerciales especializados en tareas concretas, sin una plataforma común que los integre. Quizá en un futuro próximo, presionados por una necesidad más extendida en la Creación y Gestión del Conocimiento, dispongamos de aplicaciones con más servicios de apoyo, para una Gestión Globalizada del Conocimiento, adaptados a las comunidades educativas

Molecular characterization of autophagic and apoptotic signaling induced by sorafenib in liver cancer cells

Sorafenib is the unique accepted molecular targeted drug for the treatment of patients in advanced stage of hepatocellular carcinoma. The current study evaluated cell signaling regulation of endoplasmic reticulum (ER) stress, c-Jun-N-terminal kinase (JNK), Akt, and 5′AMP-activated protein kinase (AMPK) leading to autophagy and apoptosis induced by sorafenib. Sorafenib induced early (3–12 hr) ER stress characterized by an increase of Ser51P-eIF2α/eIF2α, C/EBP homologous protein (CHOP), IRE1α, and sXBP1, but a decrease of activating transcription factor 6 expression, overall temporally associated with the increase of Thr183,Tyr185P-JNK1/2/JNK1/2, Thr172P-AMPKα, Ser413P-Foxo3a, Thr308P-AKt/AKt and Thr32P-Foxo3a/Foxo3a ratios, and reduction of Ser2481P-mammalian target of rapamycin (mTOR)/mTOR and protein translation. This pattern was related to a transient increase of tBid, Bim EL, Beclin-1, Bcl-xL, Bcl-2, autophagy markers, and reduction of myeloid cell leukemia-1 (Mcl-1) expression. The progressive increase of CHOP expression, and reduction of Thr308P-AKt/AKt and Ser473P-AKt/AKt ratios were associated with the reduction of autophagic flux and an additional upregulation of Bim EL expression and caspase-3 activity (24 hr). Small interfering-RNA (si-RNA) assays showed that Bim, but not Bak and Bax, was involved in the induction of caspase-3 in sorafenib-treated HepG2 cells. Sorafenib increased autophagic and apoptotic markers in tumor-derived xenograft model. In conclusion, the early sorafenib-induced ER stress and regulation of JNK and AMPK-dependent signaling were related to the induction of survival autophagic process. The sustained drug treatment induced a progressive increase of ER stress and PERK-CHOP-dependent rise of Bim EL, which was associated with the shift from autophagy to apoptosis. The kinetic of Bim EL expression profile might also be related to the tight balance between AKt- and AMPK-related signaling leading to Foxo3a-dependent BIM EL upregulation.Ministerio de Economía y Competitividad BFU2016‐75352‐PInstituto de Salud Carlos III PI15/00034, PI13/ 00021, PI16/00090, PI14/01349Ministerio de Educación FPU16/05127, FPU12/01433, FPU13/01237Junta de Andalucía CTS-6264, PI-00025-2013, PI-0127-2013, PI-0198-201

El método del caso en la enseñanza del Derecho Mercantil: Derecho de sociedades

Memoria del primer año de un Proyecto de Innovación Docente plurianual explicando el desarrollo y ejecución de un sistema de enseñanza de tipo angloamericano, basado en el método del caso y la dialéctica en su resolución como actividad permanente en todas las sesiones docentes, potenciando el valor de la universidad presencial

Efectos de la dieta, probióticos y prebióticos en la salud intestinal. Revisión bibliográfica.

Un gran número de interacciones y procesos ocurren en el intestino, el mismo órgano y las bacterias que contiene desempeñan un papel importante en la defensa de patógenos para garantizar así el correcto funcionamiento del sistema gastrointestinal.La microbiota intestinal nos protege de distintos agentes patógenos a través del efecto barrera y el antagonismo microbiano. Por ello, garantizar el buen equilibrio microbiano es fundamental para la salud intestinal.Es bien sabido que la dieta afecta a la microbiota intestinal, sin embargo, los efectos de sus componentes y de su acción sobre marcadores inflamatorios aún no se comprende completamente.En la presente revisión bibliográfica se buscará revisar la evidencia en la literatura respecto a los efectos de la dieta, los probióticos y prebióticos sobre la salud intestinal. Para ello, se ha seguido una metodología adecuada en cuanto a la selección de artículos y la relevancia de estos para así obtener la información actualizada sobre el tema en cuestión.<br /

Piezas

Pieza

Preliminary Studies of the Toxicity of Agaricus Bisporous Aqueous Enzymatic Extracts (AbAEE) In Rats

The health benefits of extracts from Agaricus bisporus greatly extend its use as components of new functional foods for the treatment and prevention of diseases, rather than restricting it to a good food with high nutritional value and good flavor. A. bisporus aqueous enzymatic extracts (AbAEE) have unique flavor, good taste, and health benefits which makes it a good candidate for its incorporation in different matrices for development of new functional foods and nutraceuticals. The potential use of AbAEE as nutraceutical or incorporated as a part of new functional foods requires its characterization and a subsequent food safety study. The focus of this paper was to carry out a preliminary toxicological study on experimental animals (rats in this case) by acute and sub-chronic oral administration. To evaluate potential adverse effects of AbAEE at high doses the acute toxic class method was used. After administration of the preset doses, behavior changes, toxic symptoms, and deaths were observed continuously for 1 h after treatment and then intermittently at 4th, 8th and 24th h. After these initial observations, the rats were further observed for up to 14 consecutive days for any signs of toxicity and/or death. Because of the likelihood that the results obtained in this preliminary acute toxicity test have a direct relevance for protecting human health with respect to the use of AbAEE as a functional food or nutraceutial, an additional upper dose level of 5000 mg/kg b.wt. was used. Since no death was observed, the LD50 could not be estimated but is expected to exceed 5000 mg/kg and this extract could be classified as hazard category 5 (in Globally Harmonized Classification System for Chemical Substances and Mixtures.) or even unclassified for its acute toxicity by the oral route. The sub-chronic oral toxicity study of AbAEE (250 and 500 mg/kg b.wt. day) did not induce significant alterations in almost all hematological and biochemical parameters in rats. Therefore, the overall results of the present study provide supportive data on the use of AbAEE and provide a promising first step for their use as component of new functional foods or as nutraceutical. Though, further studies in both, animals and humans are needed for better evaluation of the food safety of this extract.Ministerio de Economía y Competitividad (MINECO). España IPT- 2011-1418-060000FEDER IPT- 2011-1418-06000