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Doñinos de Salamanca, Spain

Pericacho M.,University of Salamanca | Velasco S.,University of Salamanca | Prieto M.,University of Salamanca | Llano E.,University of Salamanca | And 4 more authors.
PLoS ONE | Year: 2013

Accurate regulation of dermal fibroblast function plays a crucial role in wound healing. Many fibrotic diseases are characterized by a failure to conclude normal tissue repair and the persistence of fibroblasts inside lesions. In the present study we demonstrate that endoglin haploinsufficiency promotes fibroblast accumulation during wound healing. Moreover, scars from endoglin-heterozygous (Eng+/-) mice show persisting fibroblasts 12 days after wounding, which could lead to a fibrotic scar. Endoglin haploinsufficiency results in increased proliferation and migration of primary cultured murine dermal fibroblasts (MDFs). Moreover, Eng+/- MDF have diminished responses to apoptotic signals compared with control cells. Altogether, these modifications could explain the augmented presence of fibroblasts in Eng+/- mice wounds. We demonstrate that endoglin expression regulates Akt phosphorylation and that PI3K inhibition abolishes the differences in proliferation between endoglin haploinsufficient and control cells. Finally, persistent fibroblasts in Eng+/- mice wound co-localize with a greater degree of Akt phosphorylation. Thus, endoglin haploinsufficiency seems to promote fibroblast accumulation during wound healing through the activation of the PI3K/Akt pathway. These studies open new non-Smad signaling pathway for endoglin regulating fibroblast cell function during wound healing, as new therapeutic opportunities for the treatment of fibrotic wounds. © 2013 Pericacho et al.

Suazo V.,University of Salamanca | Suazo V.,Biomedical Research Institute of Salamanca | Diez A.,University of Salamanca | Diez A.,Biomedical Research Institute of Salamanca | And 6 more authors.
Psychiatry and Clinical Neurosciences | Year: 2014

Aims The aim of this study was to assess the relation between cognition, gray matter (GM) volumes and gamma noise power (amount of background oscillatory activity in the gamma band) in schizophrenia. Methods We explored the relation between cognitive performance and regional GM volumes using voxel-based morphometry (VBM), in order to discover if the association between gamma noise power (an electroencephalography measurement of background activity in the gamma band) and cognition is observed through structural deficits related to the disease. Noise power, magnetic resonance imaging and cognitive assessments were obtained in 17 drug-free paranoid patients with schizophrenia and 13 healthy controls. Results In comparison with controls, patients showed GM deficits at posterior cingulate (bilateral),left inferior parietal (supramarginal gyrus) and left inferior dorsolateral prefrontal regions. Patients exhibited a direct association between performance in working memory and right temporal (superior and inferior gyri) GM densities. They also displayed a negative association between right anterior cerebellum volume and gamma noise power at the frontal midline (Fz) site. Conclusion A structural deficit in the cerebellum may be involved in gamma activity disorganization in schizophrenia. Temporal structural deficits may relate to cognitive dysfunction in this illness. © 2013 The Authors.

Campo L.,Complutense University of Madrid | Aliaga I.J.,Complutense University of Madrid | De Paz J.F.,Biomedical Research Institute of Salamanca | Garcia A.E.,Complutense University of Madrid | And 4 more authors.
Computational Intelligence and Neuroscience | Year: 2016

The field of odontology requires an appropriate adjustment of treatments according to the circumstances of each patient. A follow-up treatment for a patient experiencing problems from a previous procedure such as endodontic therapy, for example, may not necessarily preclude the possibility of extraction. It is therefore necessary to investigate new solutions aimed at analyzing data and, with regard to the given values, determine whether dental retreatment is required. In this work, we present a decision support system which applies the case-based reasoning (CBR) paradigm, specifically designed to predict the practicality of performing or not performing a retreatment. Thus, the system uses previous experiences to provide new predictions, which is completely innovative in the field of odontology. The proposed prediction technique includes an innovative combination of methods that minimizes false negatives to the greatest possible extent. False negatives refer to a prediction favoring a retreatment when in fact it would be ineffective. The combination of methods is performed by applying an optimization problem to reduce incorrect classifications and takes into account different parameters, such as precision, recall, and statistical probabilities. The proposed system was tested in a real environment and the results obtained are promising. © 2016 Livia Campo et al.

Crespo I.,University of Coimbra | Vital A.L.,University of Coimbra | Gonzalez-Tablas M.,University of Salamanca | Patino M.D.C.,University of Salamanca | And 11 more authors.
American Journal of Pathology | Year: 2015

In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16INK4A, and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14ARF pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors. © 2015 American Society for Investigative Pathology.

Padron-Morales J.,University of Salamanca | Padron-Morales J.,Biomedical Research Institute of Salamanca | Garcia-Solaesa V.,University of Salamanca | Garcia-Solaesa V.,Biomedical Research Institute of Salamanca | And 14 more authors.
Allergologia et Immunopathologia | Year: 2014

Asthma is a complex disease involving numerous mediator molecules and effector cells, in combination with a range of environmental determining factors. Cytokines play a key role in the physiopathological mechanisms of asthma; the study of the structure, regulation and variations of the genes that encode for these molecules is therefore crucial. Cytokines have extremely diverse roles, and exert effects both as activators and inhibitors of the innate and adaptive immune response. Certain modifications in the expression or structure of these molecules, resulting from the presence of polymorphisms, may give rise to deregulation of the mentioned effects, and therefore to a predisposition to develop concrete asthma phenotypes. © 2013 SEICAP.

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