Construcción génica y su empleo en el tratamiento de la fibrosis cardíaca

Construcción génica y su empleo en el tratamiento de la fibrosis cardiaca. La presente invención se refiere a una nueva construcción génica que comprende a) una secuencia de ADN que codifica para la proteína proMMP2, b) una secuencia de ADN que codifica para el promotor de MHC-{be}, operativamente unida a la secuencia a), y c) un vector de expresión y secreción de proteínas que une operativamente a las secuencias a) y b). Asimismo, se contempla una composición farmacéutica, que comprende dicha construcción génica, para su empleo en el tratamiento de la fibrosis cardiaca. Finalmente se contempla el método para la obtención de la construcción génica de la invención.Solicitud: 201700440 (29.03.2017)Nº Pub. de Solicitud: ES2620702A1 (29.06.2017)Nº de Patente: ES2620702B2 (18.12.2017

Color y género. Un análisis de la pervivencia de estereotipos

En esta comunicación se analiza como los estereotipos asociados a los colores siguen vigentes en nuestra sociedad. Tradicionalmente era lo común vestir a los niños vestidos de azul y a las niñas de rosa, al igual que a los niños se les acostumbraba a regalar juguetes bélicos y las niñas muñecas. Han sido numerables las campañas en los medios de comunicación orientadas a combatir la adscripción de roles o colores según género. Sin embargo, aún permanece de forma latente la transmisión generacional de dichos estereotipos. Para llevar a cabo esta investigación, se ha elaborado un cuestionario realizado por alumnado comprendido entre los 6 y 7 años de edad. En dicho cuestionario, primero el alumnado facilitaba información acerca de los colores con los que los padres adornan su entorno (color de la habitación, de la ropa, útiles de clase, etc). Así mismo, se preguntaba al alumnado sus preferencias sobre colores a efectos de control. El análisis estadístico posterior confirma una diferencia significativa en lo que se refiere respecto a los colores que utilizan los padres para niños y niñas. Para las niñas se escogen colores cálidos y para los niños colores fríos, dando continuidad al estereotipo de color/género

Who is Transitioning out of Prison? Characterising Female Offenders and Their Needs in Chile

The last decades’ increase in female incarceration has translated into an increasing number of women being released from prison. Understanding their characteristics and criminal trajectories can enlighten us regarding the different needs of women upon re-entering society after incarceration. Drawing on data from the Reinserción, Desistimiento y Reincidencia en Mujeres Privadas de Libertad en Chile study, this article identifies different profiles among a cohort of 225 women who were released from prison in Santiago, Chile, and demonstrates that significant heterogeneity exists among them in terms of their criminal trajectories and the intervention needs to support their transition out of prison

Correlative 3D cryo X-ray imaging reveals intracellular location and effect of designed antifibrotic protein-nanomaterial hybrids

Revealing the intracellular location of novel therapeutic agents is paramount for the understanding of their effect at the cell ultrastructure level. Here, we apply a novel correlative cryo 3D imaging approach to determine the intracellular fate of a designed protein-nanomaterial hybrid with antifibrotic properties that shows great promise in mitigating myocardial fibrosis. Cryo 3D structured illumination microscopy (cryo-3D-SIM) pinpoints the location and cryo soft X-ray tomography (cryo-SXT) reveals the ultrastructural environment and subcellular localization of this nanomaterial with spatial correlation accuracy down to 70 nm in whole cells. This novel high resolution 3D cryo correlative approach unambiguously locates the nanomaterial after overnight treatment within multivesicular bodies which have been associated with endosomal trafficking events by confocal microscopy. Moreover, this approach allows assessing the cellular response towards the treatment by evaluating the morphological changes induced. This is especially relevant for the future usage of nanoformulations in clinical practices. This correlative super-resolution and X-ray imaging strategy joins high specificity, by the use of fluorescence, with high spatial resolution at 30 nm (half pitch) provided by cryo-SXT in whole cells, without the need of staining or fixation, and can be of particular benefit to locate specific molecules in the native cellular environment in bio-nanomedicine

Sex-Specific Regulation of miR-29b in the Myocardium Under Pressure Overload is Associated with Differential Molecular, Structural and Functional Remodeling Patterns in Mice and Patients with Aortic Stenosis

Pressure overload in patients with aortic stenosis (AS) induces an adverse remodeling of the left ventricle (LV) in a sex-specific manner. We assessed whether a sex-specific miR-29b dysregulation underlies this sex-biased remodeling pattern, as has been described in liver fibrosis. We studied mice with transverse aortic constriction (TAC) and patients with AS. miR-29b was determined in the LV (mice, patients) and plasma (patients). Expression of remodeling-related markers and histological fibrosis were determined in mouse LV. Echocardiographic morpho-functional parameters were evaluated at baseline and post-TAC in mice, and preoperatively and 1 year after aortic valve replacement (AVR) in patients with AS. In mice, miR-29b LV regulation was opposite in TAC-males (down-regulation) and TAC-females (up-regulation). The subsequent changes in miR-29b targets (collagens and GSK-3?) revealed a remodeling pattern that was more fibrotic in males but more hypertrophic in females. Both systolic and diastolic cardiac functions deteriorated more in TAC-females, thus suggesting a detrimental role of miR-29b in females, but was protective in the LV under pressure overload in males. Clinically, miR-29b in controls and patients with AS reproduced most of the sexually dimorphic features observed in mice. In women with AS, the preoperative plasma expression of miR-29b paralleled the severity of hypertrophy and was a significant negative predictor of reverse remodeling after AVR; therefore, it may have potential value as a prognostic biomarker

Androgens contribute to sex differences in myocardial remodeling under pressure overload by a mechanism involving TGF-beta

Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Methodology/principal findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-?s, Smads 2 and 3, collagens, fibronectin, ?-myosin heavy chain and ?-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson's trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-?s and the treatment with a neutralizing antibody to TGF-? prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-?s and TGF-? target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-? expression was confirmed in NIH-3T3 fibroblasts and H9C2 cardiomyocytes exposed to dihydrotestosterone. Conclusions/significance: Our results indicate that circulating androgens are responsible for the detrimental effects in the myocardium of older male mice subjected to pressure overload through a mechanism involving TGF-?s.This work was supported by Instituto de Salud Carlos III (PS09/01097); Fundación Marqués de Valdecilla-Universidad de Cantabria (FMV-UC 09/01); Instituto de Formación e Investigación Marqués de Valdecilla (FMV-API 10/20); and Ministerio de Ciencia e Innovación (SAF2010-16894). Dr. Nistal is in the Scientist Stabilization and Research Activity Intensification Program of the National Health System, funded by the Instituto de Salud Carlos III and Comunidad Autónoma de Cantabria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Spontaneous rectus sheath hematoma : case report.

O hematoma espont?neo do m?sculo reto abdominal ? uma condi??o rara, - 1/10.000 de todas as urg?ncias - causado pelo ac?mulo de sangue em sua pr?pria bainha muscular por causa de rompimento dos vasos epig?stricos ou por les?o da pr?pria musculatura. O presente estudo tem o objetivo de relatar um caso de hematoma espont?neo do m?sculo reto abdominal raro e discorrer sobre suas poss?veis aplica??es cl?nicas. Este artigo relata um caso de uma mulher de 47 anos que deu entrada no Hospital P?blico Regional de Betim Osvaldo Rezende Franco (HPRB) apresentando intensa dor abdominal e equimose epig?strica com achados de hematoma na bainha do m?sculo reto do abdome em exames de imagem. A paciente foi submetida a tratamento convencional ap?s tomografia computadorizada de abdome superior evidenciar a afec??o. Ressalta-se a import?ncia do reconhecimento do quadro na pr?tica cl?nica, pois sua semelhan?a com outras condi??es abdominais agudas pode levar a interven??es cir?rgicas desnecess?rias.The Spontaneous hematoma of the rectus abdominis muscle is a rare condition -1 / 10,000 of all urgencies - caused by the accumulation of blood in its own muscular sheath due to the rupture of the epigastric vessels or injury of the musculature itself. The present study aims to report a rare case of spontaneous hematoma of the rectus abdominis muscle and to discuss its possible clinical applications. This article reports a case of a 47-year-old woman who was admitted at Regional Public Hospital of Betim Osvaldo Rezende Franco (HPRB) presenting severe abdominal pain and epigastric ecchymosis with hematoma findings in the sheath of the rectus abdominis muscle at imaging examinations. The patient was submitted to conventional treatment after computed tomography of the upper abdomen evidenced the condition. Therefore, it is important to recognize the clinical picture in clinical practice, since its similarity with other acute abdominal conditions can lead to unnecessary surgical interventions

Identification of a Novel Modulator of Thyroid Hormone Receptor-Mediated Action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease

BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) reveals the involvement of the transforming growth factor-beta family in pain modulation

Transforming growth factors- (TGF- s) signal through type I and type II serine–threonine kinase receptor complexes. During ligand binding, type II receptors recruit and phosphorylate type I receptors, triggering downstream signaling. BAMBI [bone morphogenetic protein (BMP) and activin membrane-bound inhibitor] is a transmembrane pseudoreceptor structurally similar to type I receptors but lacks the intracellular kinase domain. BAMBI modulates negatively pan-TGF- family signaling; therefore, it can be used as an instrument for unraveling the roles of these cytokines in the adult CNS. BAMBI is expressed in regions of the CNS involved in pain transmission and modulation. The lack of BAMBI in mutant mice resulted in increased levels of TGF- signaling activity, which was associated with attenuation of acute pain behaviors, regardless of the modality of the stimuli (thermal, mechanical, chemical/inflammatory). The nociceptive hyposensitivity exhibited by BAMBI / mice was reversed by the opioid antagonist naloxone. Moreover, in a model of chronic neuropathic pain, the allodynic responses of BAMBI / mice also appeared attenuated through a mechanism involving -opioid receptor signaling. BasalmRNAand protein levels of precursor proteins of the endogenous opioid peptides proopiomelanocortin (POMC) and proenkephalin (PENK) appeared increased in the spinal cords of BAMBI / . Transcript levels of TGF- s and their intracellular effectors correlated directly with genes encoding opioid peptides, whereas BAMBI correlated inversely. Furthermore, incubation of spinal cord explants with activin A or BMP-7 increased POMC and/or PENK mRNA levels. Our findings identify TGF- family members as modulators of acute and chronic pain perception through the transcriptional regulation of genes encoding the endogenous opioids

Identification of a novel modulator of thyroid hormone receptor-mediated action

Diabetes is characterized by reduced thyroid function and altered myogenesis after muscle injury. Here we identify a novel component of thyroid hormone action that is repressed in diabetic rat muscle. Methodology/Principal Findings. We have identified a gene, named DOR, abundantly expressed in insulin-sensitive tissues such as skeletal muscle and heart, whose expression is highly repressed in muscle from obese diabetic rats. DOR expression is up-regulated during muscle differentiation and its loss-of-function has a negative impact on gene expression programmes linked to myogenesis or driven by thyroid hormones. In agreement with this, DOR enhances the transcriptional activity of the thyroid hormone receptor TRa1. This function is driven by the N-terminal part of the protein. Moreover, DOR physically interacts with TR a1 and to T3-responsive promoters, as shown by ChIP assays. T3 stimulation also promotes the mobilization of DOR from its localization in nuclear PML bodies, thereby indicating that its nuclear localization and cellular function may be related. Conclusions/Significance. Our data indicate that DOR modulates thyroid hormone function and controls myogenesis. DOR expression is down-regulated in skeletal muscle in diabetes. This finding may be of relevance for the alterations in muscle function associated with this disease