Mechanisms of endothelial cell protection by blockade of the JAK2 pathway

10 pages, 7 figures.Inhibition of the JAK2/STAT pathway has been implicated recently in cytoprotective mechanisms in both vascular smooth muscle cells and astrocytes. The advent of JAK2-specific inhibitors provides a practical tool for the study of this pathway in different cellular types. An interest in finding methods to improve endothelial cell (EC) resistance to injury led us to examine the effect of JAK2/STAT inhibition on EC protection. Furthermore, the signaling pathways involved in JAK2/STAT inhibition-related actions were examined. Our results reveal, for the first time, that blockade of JAK2 with the tyrosine kinase inhibitor AG490 strongly protects cultured EC against cell detachment-dependent death and serum deprivation and increases reseeding efficiency. Confirmation of the specificity of the effects of JAK2 inhibition was attained by finding protective effects on transfection with a dominant negative JAK2. Furthermore, AG490 blocked serum deprivation-induced phosphorylation of JAK2. In terms of mechanism, treatment with AG490 induces several relevant responses, both in monolayer and detached cells. These mechanisms include the following: 1) Increase and nuclear translocation of the active, dephosphorylated form of beta-catenin. In functional terms, this translocation is transcriptionally active, and its protective effect is further supported by the stimulation of EC cytoprotection by transfectionally induced excess of beta-catenin. 2) Increase of platelet endothelial cell adhesion molecule (PECAM)/CD31 levels. 3) Increase in total and phosphorylated AKT. 4) Increase in phosphorylated glycogen synthase kinase (GSK)3alpha/beta. The present findings imply potential practical applications of JAK2 inhibition on EC. These applications affect not only EC in the monolayer but also circulating detached cells and involve mechanistic interactions not previously described.This study was supported by grants from the Instituto de Salud Carlos III (Red Cardiovascular), Fondo de Investigaciones Sanitarias (FIS: PI: 030888), Comunidad Autónoma de Madrid (CAM: GR/SAL/0418/2004), Sociedad Española de Nefrología and Instituto Reina Sofía de Investigación Nefrológica (IRSIN, Entrecanales Trust), the Spanish Ministry of Education, Science and Technology (SAF04-00361), Fundación Jiménez Díaz-Capio and Amgen (Barcelona, Spain). M. A. Castilla and F. R. González-Pacheco are investigators from FIS and CAM, respectively. S. Peñate is a senior research technician from Red Cardiovascular (RECAVA), and J. J. P. Deudero is a fellow from the Instituto Carlos III. F. Neria, A. J. de Solis, and R. Fernández-Sánchez are fellows from Fundación C. Rábago. H. Peinado is supported by a grant from Justesa Imagen SA.Peer reviewe

Evaluar el comportamiento de la chiltoma (Capsicum Annum L) variedad tres cantos bajo el sistema convencional vs orgánico en La Quinta Vera, comarca Santa Rita Km 147½ carretera Juigalpa-El Rama en el primer semestre del 2016

Este experimento fue realizado en La Quinta Vera Comarca Santa Rita Km 147 ½ carretera El Rama Juigalpa - Chontales, en los meses de Febrero a Junio del 2016. Un diseño de Bloque Completo al Azar con chiltoma (Capsicum annum L) fue desarrollado comparando tres diferentes tratamientos, con el objetivo de valorar el rendimiento productivo del cultivo. Los tratamientos a evaluar fueron; T1, tratamiento orgánico aplicando lombrihumus; T2, tratamiento químico aplicando fertilizante completo (NPK) 15-15-15 y; T3, un tratamiento testigo. Para todos los tratamientos se utilizó estiércol al momento de realizar el semillero y actividades culturales propias del cultivo. Los datos fueron procesados por IBM SPSS Statistics 18.0 de Chicago, USA, para Windows. Las variables evaluadas fueron cantidad de chiltoma por plantas, cantidad de chiltoma por surco, tamaño de la chiltoma, altura de la planta y peso de la chiltoma; además de ello, se identificaron y controlaron las principales plagas y enfermedades que atacan al cultivo. Se aplicó un ANOVA de un factor con efecto fijo donde se usó como variable dependiente el total de muestras de chiltoma y variable independiente el tipo de tratamiento. En la variable de tratamiento, el mejor resultado en cuanto a altura fue el orgánico con una media de 22.9 cm seguido del tratamiento químico con 22.7 cm y finalmente el testigo con 19.4 cm. Al determinar el número promedio de frutos por planta, se obtuvo para el tratamiento químico 2.22, orgánico 2.07 y 1.56 para el testigo. En cuanto al tamaño promedio del fruto por planta fue para el orgánico de 5.3cm, para el químico 3.01cm y el testigo con 2.66cm.Por último, para la variable peso, se obtuvo para el orgánico frutos de 33.72gr, seguido del testigo con 14.47gr y el químico con 13.84gr. Palabras claves: Capsicum annum L, Variedad, Plagas, Enfermedad, Producció

TEO: an online emotional therapy system to apply homework assignments in the Treatment of adjustment disorders

Adjustment Disorders (AD) are a very important public health problem. Regarding its treatment, only a series of general guidelines are available. Our research team has developed a cognitive-behavioral treatment (CBT) supported by Virtual Reality (VR) that has shown its utility in the treatment of AD. A CBT approach gives a crucial role to homework assignments. So far, studies that use Information and Communication Technologies (ICT) for psychological treatments have been centered on how to use the technologies to deliver treatment within the therapeuti c c ontext. No study is avai lable in the literature that uses ICT to apply homework assignments. Therefore, in the present work we pretend to go one step beyond and join the use of the VR EMMA system within the therapy sessions, with the use of other ICT to apply homework assignments between sessions in the treatment of AD. TEO is a completely open Online Emotional Therapy system based on Web technology that allows, in a simple and effective way, to create personalized therapeutic material to present to the patient over the Internet. The aim of the present work is to describe the TEO system and the study that is being conducted to test its efficacy and efficiency

MicroRNA-200 Family Modulation in Distinct Breast Cancer Phenotypes

The epithelial to mesenchymal transition (EMT) contributes to tumor invasion and metastasis in a variety of cancer types. In human breast cancer, gene expression studies have determined that basal-B/claudin-low and metaplastic cancers exhibit EMT-related characteristics, but the molecular mechanisms underlying this observation are unknown. As the family of miR-200 microRNAs has been shown to regulate EMT in normal tissues and cancer, here we evaluated whether the expression of the miR-200 family (miR-200f) and their epigenetic state correlate with EMT features in human breast carcinomas. We analyzed by qRT-PCR the expression of miR-200f members and various EMT-transcriptional inducers in a series of 70 breast cancers comprising an array of phenotypic subtypes: estrogen receptor positive (ER+), HER2 positive (HER2+), and triple negative (TN), including a subset of metaplastic breast carcinomas (MBCs) with sarcomatous (homologous or heterologous) differentiation. No MBCs with squamous differentiation were included. The DNA methylation status of miR-200f loci in tumor samples were inspected using Sequenom MassArray® MALDI-TOF platform. We also used two non-tumorigenic breast basal cell lines that spontaneously undergo EMT to study the modulation of miR-200f expression during EMT in vitro. We demonstrate that miR-200f is strongly decreased in MBCs compared with other cancer types. TN and HER2+ breast cancers also exhibited lower miR-200f expression than ER+ tumors. Significantly, the decreased miR-200f expression found in MBCs is accompanied by an increase in the expression levels of EMT-transcriptional inducers, and hypermethylation of the miR-200c-141 locus. Similar to tumor samples, we demonstrated that downregulation of miR-200f and hypermethylation of the miR-200c-141 locus, together with upregulation of EMT-transcriptional inducers also occur in an in vitro cellular model of spontaneous EMT. Thus, the expression and methylation status of miR-200f could be used as hypothetical biomarkers to assess the occurrence of EMT in breast cancer. © 2012 Castilla et al.This work was supported by grants from: the Instituto de Salud Carlos III (ISCIII; Grant Nos PI07/90324 and PI080971) and the Ministerio de Ciencia e Innovación (MCINN), co-financed by the European Development Regional Fund, “A way to achieve Europe” EDRF (Grant No. RD06/0020/0013); the Junta de Andalucía (Consejería de Salud, Grant No.PI-0384/2007, PI0581/2009); the Consejería de Innovación (Proyecto de Excelencia, Grant No. P07-CVI-03100); and Sandra Ibarra Foundation (Grant No. 2011/088) to JP. MAC and JDM are PhD researchers funded by the ISCIII (Grant No. RD06/0020/0013) and the Consejería de Salud, Junta de Andalucía (PI0581/2009), respectively. DS was funded by an EU Marie Curie Intra-European Fellowship (PIEF-GA-2008-221083) and by Breakthrough Breast Cancer. LRP is a PhD student recipient of a PFIS fellowship (Grant No. F109/00193). MB is a researcher funded by the ISCIII-Red de Biobancos RD09/0076/00085. SR works as a lab technician supported by the ISCIII (PI080971). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe

Removal of Phenolic Compounds from Water Using Copper Ferrite Nanosphere Composites as Fenton Catalysts

The authors affiliated to the University of Jaén (Department of Inorganic and Organic Chemistry) acknowledge financial support from the Spanish Ministry of Economy, Industry and Competitiveness and from FEDER (Project CTQ2016-80978-C2-1-R). L. Mateus thanks the Asociación Universitaria Iberoamericana de Postgrado (AUIP) and University of Jaén for their grant and financial support.Copper ferrites containing Cu+ ions can be highly active heterogeneous Fenton catalysts due to synergic effects between Fe and Cu ions. Therefore, a method of copper ferrite nanosphere (CFNS) synthesis was selected that also permits the formation of cuprite, obtaining a CFNS composite that was subsequently calcined up to 400 °C. Composites were tested as Fenton catalysts in the mineralization of phenol (PHE), p-nitrophenol (PNP) and p-aminophenol (PAP). Catalysts were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and magnetic measurements. Degradation of all phenols was practically complete at 95% total organic carbon (TOC) removal. Catalytic activity increased in the order PHE < PNP < PAP and decreased when the calcination temperature was raised; this order depended on the electronic effects of the substituents of phenols. The as-prepared CFNS showed the highest catalytic activity due to the presence of cubic copper ferrite and cuprite. The Cu+ surface concentration decreased after calcination at 200 °C, diminishing the catalytic activity. Cuprite alone showed a lower activity than the CFNS composite and the homogeneous Fenton reaction had almost no influence on its overall activity. CFNS activity decreased with its reutilization due to the disappearance of the cuprite phase. Degradation pathways are proposed for the phenols.This research was funded by Spanish Ministry of Economy, Industry and Competitiveness and FEDER (grant number CTQ2016-80978-C2-1-R), Asociación Universitaria Iberoamericana de Postgrado (AUIP) and University of Jaén

Youth’s cultural leisure, a subjective indicator of human development

El ocio cultural reporta numerosos beneficios que contribuyen al crecimiento personal en sus distintas dimensiones. El objetivo de este estudio es identificar la práctica de ocio cultural de la juventud como un indicador subjetivo del desarrollo humano, mediante el análisis de la percepción que el joven tiene sobre el influjo que estas experiencias ejercen en su dimensión física, psicológica, cognitiva y social. Se aplicó un cuestionario elaborado ad hoc a una muestra de 1023 jóvenes españoles. Las actividades culturales de ocio son importantes para la juventud, quien percibe que su práctica favorece su desarrollo humano, fundamentalmente en los aspectos psicológicos, emocionales, creativos y cognitivos.Cultural leisure provides numerous benefits that contribute to personal growth in its various dimensions. The goal of this study is to identify the practice of youth’s cultural leisure as a subjective indicator of human development, through the analysis of young people's perception of the influence of such experiences on their physical, psychological, cognitive and social dimensions. An ad hoc questionnaire was administered to a sample of 1023 young Spaniards. Cultural leisure activities are important for youth, who perceive that its practice favors human development, primarily the psychological, emotional, creative and cognitive aspects.Ministerio de Economía y Competitividad, y Fondo Europeo de Desarrollo Regional (FEDER). Plan Nacional I+D+I. Proyectos de investigación «De los tiempos educativos a los tiempos sociales: la cotidianidad familiar en la construcción del ocio físico-deportivo juvenil» (EDU2012-39080-C07-05) y «Ocio y bienestar en clave intergeneracional: de la cotidianidad familiar a la innovación social en las redes abuelos-nietos» (EDU2017-85642-R).peerReviewe

Endoluminal brachytherapy in the treatment of oesophageal cancer. Technique description, case report and review of the literature.

Endoesophageal brachytherapy is a useful technique for the palliative treatment of dysphagia in advanced oesophageal cancer. This technique offers good results on dysphagia control and quality of life.We report the case of a patient treated with this technique presenting complete response to the dysphagia. We describe endoesophageal brachyterapy technique and we comment on the literature

Practical training of university students and professional deontology

Este artículo presenta una investigación dirigida a: 1) analizar los prácticum de diferentes carreras universitarias, 2) analizar las dimensiones éticas de los códigos deontológicos de profesiones universitarias, 3) comparar estas dimensiones con el entrenamiento práctico de las carreras universitarias y 5) ofrecer propuestas para mejorar los prácticum de estas carreras universitarias de acuerdo con las dimensiones éticas percibidas. Se realizó un análisis de contenido de los códigos deontológicos de siete carreras universitarias y se aplicaron a 1.454 estudiantes universitarios un cuestionario y un inventario de creencias. Los datos resultantes fueron sistemáticamente analizados (un análisis descriptivo general, un análisis descriptivo de cada carrera, análisis factoriales y análisis de contingencias) aplicando el programa SPSS. Se presentan los resultados y las conclusiones inferidas, junto a las propuestas de mejora de acuerdo con las deficiencias observadas.This paper presents a study which aimed to: 1) analyse practicums of different university degrees, 2) analyse the ethical dimensions of the deontological codes of university professions, 3) compare these dimensions with the practical training of university degrees and 4) offer proposals to improve the practicums of these university degrees according to the ethical dimensions perceived. An analysis of the contents of the deontological codes of seven university degrees was carried out, a questionnaire and an inventory of beliefs were drawn up which were presented to 1454 undergraduates. The resulting data were statistically analysed (a general descriptive analysis, an analysis of each respective degree, factor analyses and contingency analyses) by applying the SPSS programme. The results and the inferred conclusions are presented with the proposals for improvement in accordance with the observed deficiencies.Programa Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica del Ministerio de Ciencia y Tecnología (Número de referencia: BSO2001-3083)

A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155)