99 research outputs found

    Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

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    Connective tissue is known to provide structural and functional 'glue' properties to other tissues. It contains cellular and molecular components that are arranged in several dynamic organizations. Connective tissue is the focus of numerous genetic and nongenetic diseases. Genetic diseases of the connective tissue are minority or rare, but no less important than the nongenetic diseases. Here we review the impact of reactive oxygen species (ROS) and oxidative stress on the onset and/or progression of diseases that directly affect connective tissue and have a genetic origin. It is important to consider that ROS and oxidative stress are not synonymous, although they are often closely linked. In a normal range, ROS have a relevant physiological role, whose levels result from a fine balance between ROS producers and ROS scavenge enzymatic systems. However, pathology arises or worsens when such balance is lost, like when ROS production is abnormally and constantly high and/or when ROS scavenge (enzymatic) systems are impaired. These concepts apply to numerous diseases, and connective tissue is no exception. We have organized this review around the two basic structural molecular components of connective tissue: The ground substance and fibers (collagen and elastic fibers)

    Desconexión entre actores: percepciones del uso de tecnologías educativas durante la pandemia por COVID-19

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    This article studies the relationships between the actors involved in the integration of Information and Communication Technologies (ICTs) into the educational process, from their design to their implementation and use by teachers and students. This study is based on the assumption that, in the introduction of a new technology, different intentions can be identified, bringing into play the elements considered by each one of the actors involved. This paper analyzes a study case, i.e., the Vermont School in Medellín from 2020 to 2021, to explore a particular scenario of complete access to ICTs, as well as the new virtual environments and dynamics resulting from confinement as a strategy to prevent COVID-19 spread. Using surveys, interviews, and focus groups, the authors describe the new telematic environments, as well as the perceptions and relationships of designers, students, and teachers around the use of educational technologies. The results show that the introduction of technologies into education produces changes in the relationships between designers, teachers, and students because different elements modify the perceptions, intentions, and educational expectations of each actor. Consequently, when ICTs are integrated into education, designers, implementers, and users should agree on shared criteria. This integration should also consider the curriculum, the technological tool or platform, and the intentions of each actor.El objetivo de este artículo fue identificar las relaciones que se presentan entre los actores involucrados en la integración de tecnologías de la información y la comunicación al proceso educativo, desde su diseño, hasta su implementación y uso por parte de docentes y estudiantes. Se partió del supuesto de que, en la inserción de una nueva tecnología, se pueden identificar diferentes intenciones, entrando en juego los elementos considerados por cada uno de los actores. Se analizó el caso de estudio del Vermont School de Medellín entre los años 2020 y 2021. Esto permitió explorar un escenario particular de acceso completo a las TIC, así como los nuevos entornos y dinámicas virtuales resultado del confinamiento como estrategia de prevención por la COVID-19. Por medio de encuestas, entrevistas y grupos focales se logró describir los nuevos entornos telemáticos, así como las percepciones y relaciones de diseñadores, estudiantes y docentes alrededor del uso de tecnologías educativas. Los resultados mostraron que la inserción de tecnologías en la educación genera cambios en las relaciones entre diseñadores, docentes y estudiantes a partir de la consideración de diferentes elementos que modifican las percepciones, intenciones y expectativas de cada actor. En consecuencia, es fundamental la unificación de criterios al integrar las TIC al contexto educativo, desde quien diseña, quien implementa y, finalmente, quien las usa. Para esto es determinante tener en cuenta el currículo, la herramienta o plataforma tecnológica, así como las intenciones de cada actor

    Gestión de los directivos y las relaciones humanas de los docentes en las instituciones educativas públicas del cercado de Villa María del Triunfo Ugel 01.2011

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    La presente investigación tuvo como objetivo principal determinar si existe relación significativa entre la gestión de los directivos y las relaciones humanas de los docentes en las Instituciones Educativas Públicas del cercado de Villa María del Triunfo UGEL 01-2011. El tipo de investigación fue descriptivo correlacional, que se resolvió con el método cuantitativo, utilizando técnicas como: la encuesta y el cuestionario, como instrumento de investigación, las que se aplicaron a los docentes de las Instituciones Educativas Públicas del cercado de Villa María del Triunfo. El estudio contempla una población que involucra a docentes de las Instituciones Educativas Públicas del cercado de Villa María del Triunfo, la muestra estuvo constituida por 164 docentes de una población total de 286. Se aplicó la encuesta a toda la muestra, la cual nos permitió recoger la información y medir las variables para efectuar las correlaciones y las comparaciones correspondientes. En los resultados de la prueba de hipótesis se obtuvo un coeficiente de correlación de Rho de Spearman r =0,953, con un nivel de significancia del 0,05 y (p<05) corroborando aspectos señalados en la hipótesis; que la gestión de los directivos se relaciona significativamente con las relaciones humanas de los docentes en las Instituciones Educativas Públicas del Cercado de Villa María del Triunfo

    The Combined Treatment of Curcumin with Verapamil Ameliorates the Cardiovascular Pathology in a Williams-Beuren Syndrome Mouse Model

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    Williams-Beuren syndrome (WBS) is a rare disorder caused by a recurrent microdeletion with hallmarks of cardiovascular manifestations, mainly supra-valvular aortic stenosis (SVAS). Unfortunately, there is currently no efficient treatment. We investigated the effect of chronic oral treatment with curcumin and verapamil on the cardiovascular phenotype of a murine model of WBS harbouring a similar deletion, CD (complete deletion) mice. We analysed systolic blood pressure in vivo and the histopathology of the ascending aorta and the left ventricular myocardium to determine the effects of treatments and their underlying mechanism. Molecular analysis showed significantly upregulated xanthine oxidoreductase (XOR) expression in the aorta and left ventricular myocardium of CD mice. This overexpression is concomitant with increased levels of nitrated proteins as a result of byproduct-mediated oxidative stress damage, indicating that XOR-generated oxidative stress impacts the pathophysiology of cardiovascular manifestations in WBS. Only the combined therapy of curcumin and verapamil resulted in a significant improvement of cardiovascular parameters via activation of the nuclear factor erythroid 2 (NRF2) and reduction of XOR and nitrated protein levels. Our data suggested that the inhibition of XOR and oxidative stress damage could help prevent the severe cardiovascular injuries of this disorder

    Hyperuricaemia Does Not Interfere with Aortopathy in a Murine Model of Marfan Syndrome

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    Redox stress is involved in the aortic aneurysm pathogenesis in Marfan syndrome (MFS). We recently reported that allopurinol, a xanthine oxidoreductase inhibitor, blocked aortopathy in a MFS mouse model acting as an antioxidant without altering uric acid (UA) plasma levels. Hyperuricaemia is ambiguously associated with cardiovascular injuries as UA, having antioxidant or pro-oxidant properties depending on the concentration and accumulation site. We aimed to evaluate whether hyperuricaemia causes harm or relief in MFS aortopathy pathogenesis. Two-month-old male wild-type (WT) and MFS mice (Fbn1C1041G/+) were injected intraperitoneally for several weeks with potassium oxonate (PO), an inhibitor of uricase (an enzyme that catabolises UA to allantoin). Plasma UA and allantoin levels were measured via several techniques, aortic root diameter and cardiac parameters by ultrasonography, aortic wall structure by histopathology, and pNRF2 and 3-NT levels by immunofluorescence. PO induced a significant increase in UA in blood plasma both in WT and MFS mice, reaching a peak at three and four months of age but decaying at six months. Hyperuricaemic MFS mice showed no change in the characteristic aortic aneurysm progression or aortic wall disarray evidenced by large elastic laminae ruptures. There were no changes in cardiac parameters or the redox stress-induced nuclear translocation of pNRF2 in the aortic tunica media. Altogether, the results suggest that hyperuricaemia interferes neither with aortopathy nor cardiopathy in MFS mice

    The undiscovered biosynthetic potential of the Greenland Ice Sheet microbiome

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    The Greenland Ice Sheet is a biome which is mainly microbially driven. Several different niches can be found within the glacial biome for those microbes able to withstand the harsh conditions, e.g., low temperatures, low nutrient conditions, high UV radiation in summer, and contrasting long and dark winters. Eukaryotic algae can form blooms during the summer on the ice surface, interacting with communities of bacteria, fungi, and viruses. Cryoconite holes and snow are also habitats with their own microbial community. Nevertheless, the microbiome of supraglacial habitats remains poorly studied, leading to a lack of representative genomes from these environments. Under-investigated extremophiles, like those living on the Greenland Ice Sheet, may provide an untapped reservoir of chemical diversity that is yet to be discovered. In this study, an inventory of the biosynthetic potential of these organisms is made, through cataloging the presence of biosynthetic gene clusters in their genomes. There were 133 high-quality metagenome-assembled genomes (MAGs) and 28 whole genomes of bacteria obtained from samples of the ice sheet surface, cryoconite, biofilm, and snow using culturing-dependent and -independent approaches. AntiSMASH and BiG-SCAPE were used to mine these genomes and subsequently analyze the resulting predicted gene clusters. Extensive sets of predicted Biosynthetic Gene Clusters (BGCs) were collected from the genome collection, with limited overlap between isolates and MAGs. Additionally, little overlap was found in the biosynthetic potential among different environments, suggesting specialization of organisms in specific habitats. The median number of BGCs per genome was significantly higher for the isolates compared to the MAGs. The most talented producers were found among Proteobacteria. We found evidence for the capacity of these microbes to produce antimicrobials, carotenoid pigments, siderophores, and osmoprotectants, indicating potential survival mechanisms to cope with extreme conditions. The majority of identified BGCs, including those in the most prevalent gene cluster families, have unknown functions, presenting a substantial potential for bioprospecting. This study underscores the diverse biosynthetic potential in Greenland Ice Sheet genomes, revealing insights into survival strategies and highlighting the need for further exploration and characterization of these untapped resources

    Allopurinol blocks aortic aneurysm in a mouse model of Marfan syndrome via reducing aortic oxidative stress

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    Background Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen species (ROS) formation and NADPH oxidase NOX4 upregulation in MFS patients and mouse aortae. Here we address the contribution of xanthine oxidoreductase (XOR), which catabolizes purines into uric acid and ROS in MFS aortopathy. Methods and results In aortic samples from MFS patients, XOR protein expression, revealed by immunohistochemistry, increased in both the tunicae intima and media of the dilated zone. In MFS mice (Fbn1C1041G/+), aortic XOR mRNA transcripts and enzymatic activity of the oxidase form (XO) were augmented in the aorta of 3-month-old mice but not in older animals. The administration of the XOR inhibitor allopurinol (ALO) halted the progression of aortic root aneurysm in MFS mice. ALO administrated before the onset of the aneurysm prevented its subsequent development. ALO also inhibited MFS-associated endothelial dysfunction as well as elastic fiber fragmentation, nuclear translocation of pNRF2 and increased 3′-nitrotyrosine levels, and collagen maturation remodeling, all occurring in the tunica media. ALO reduced the MFS-associated large aortic production of H2O2, and NOX4 and MMP2 transcriptional overexpression. Conclusions Allopurinol interferes in aortic aneurysm progression acting as a potent antioxidant. This study strengthens the concept that redox stress is an important determinant of aortic aneurysm formation and progression in MFS and warrants the evaluation of ALO therapy in MFS patients

    Application of the adverse outcome pathway to identify molecular changes in prenatal brain programming induced by IUGR: Discoveries after EGCG exposure

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    Following a multi-disciplinary approach integrating information from several experimental models we have collected new evidence supporting, expanding and redesigning the AOP "Disrupted laminin/int-β1 interaction leading to decreased cognitive function". Investigations in vitro in rabbit and rat neurospheres and in vivo in mice exposed to EGCG (epigallocatechin-gallate) during neurodevelopment are combined with in vitro evaluations in neural progenitor cells overexpressing int-β1 and literature information from int-β1 deficiency models. We have discovered for the first time that neural progenitor cells from intrauterine growth restricted (IUGR) animals overexpress int-β1 at gene and protein level and due to this change in prenatal brain programming they respond differently than control neurospheres to the exposure of EGCG, a compound triggering neural progenitor cell migration alterations. We have also identified that EGCG developmental exposure has deleterious effects on neuronal branching and arborization in vitro and in vivo. Our results warn that a thorough developmental neurotoxicity characterization of this and other catechin-based food supplements is needed before recommending their consumption during pregnancy
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