MicroRNA133 and microRNA499 exert synergistic effect on cardiac differentiation

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Inflammatory extracellular vesicles prompt heart dysfunction via TRL4-dependent NF-κB activation.

Background: After myocardial infarction, necrotic cardiomyocytes release damage-associated proteins that stimulate innate immune pathways and macrophage tissue infiltration, which drives inflammation and myocardial remodeling. Circulating inflammatory extracellular vesicles play a crucial role in the acute and chronic phases of ischemia, in terms of inflammatory progression. In this study, we hypothesize that the paracrine effect mediated by these vesicles induces direct cytotoxicity in cardiomyocytes. Thus, we examined whether reducing the generation of inflammatory vesicles within the first few hours after the ischemic event ameliorates cardiac outcome at short and long time points. Methods: Myocardial infarction was induced in rats that were previously injected intraperitoneally with a chemical inhibitor of extracellular-vesicle biogenesis. Heart global function was assessed by echocardiography performed at 7, 14 and 28 days after MI. Cardiac outcome was also evaluated by hemodynamic analysis at sacrifice. Cytotoxic effects of circulating EV were evaluated ex-vivo in a Langendorff, system by measuring the level of cardiac troponin I (cTnI) in the perfusate. Mechanisms undergoing cytotoxic effects of EV derived from pro-inflammatory macrophages (M1) were studied in-vitro in primary rat neonatal cardiomyocytes. Results: Inflammatory response following myocardial infarction dramatically increased the number of circulating extracellular vesicles carrying alarmins such as IL-1α, IL-1β and Rantes. Reducing the boost in inflammatory vesicles during the acute phase of ischemia resulted in preserved left ventricular ejection fraction in vivo. Hemodynamic analysis confirmed functional recovery by displaying higher velocity of left ventricular relaxation and improved contractility. When added to the perfusate of isolated hearts, post-infarction circulating vesicles induced significantly more cell death in adult cardiomyocytes, as assessed by cTnI release, comparing to circulating vesicles isolated from healthy (non-infarcted) rats. In vitro inflammatory extracellular vesicles induce cell death by driving nuclear translocation of NF-κB into nuclei of cardiomyocytes. Conclusion: Our data suggest that targeting circulating extracellular vesicles during the acute phase of myocardial infarction may offer an effective therapeutic approach to preserve function of ischemic heart

Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction.

AIMS: Recent evidence suggests that cardiac progenitor cells (CPCs) may improve cardiac function after injury. The underlying mechanisms are indirect, but their mediators remain unidentified. Exosomes and other secreted membrane vesicles, hereafter collectively referred to as extracellular vesicles (EVs), act as paracrine signalling mediators. Here, we report that EVs secreted by human CPCs are crucial cardioprotective agents. METHODS AND RESULTS: CPCs were derived from atrial appendage explants from patients who underwent heart valve surgery. CPC-conditioned medium (CM) inhibited apoptosis in mouse HL-1 cardiomyocytic cells, while enhancing tube formation in human umbilical vein endothelial cells. These effects were abrogated by depleting CM of EVs. They were reproduced by EVs secreted by CPCs, but not by those secreted by human dermal fibroblasts. Transmission electron microscopy and nanoparticle tracking analysis showed most EVs to be 30-90 nm in diameter, the size of exosomes, although smaller and larger vesicles were also present. MicroRNAs most highly enriched in EVs secreted by CPCs compared with fibroblasts included miR-210, miR-132, and miR-146a-3p. miR-210 down-regulated its known targets, ephrin A3 and PTP1b, inhibiting apoptosis in cardiomyocytic cells. miR-132 down-regulated its target, RasGAP-p120, enhancing tube formation in endothelial cells. Infarcted hearts injected with EVs from CPCs, but not from fibroblasts, exhibited less cardiomyocyte apoptosis, enhanced angiogenesis, and improved LV ejection fraction (0.8 ± 6.8 vs. -21.3 ± 4.5%; P < 0.05) compared with those injected with control medium. CONCLUSION: EVs are the active component of the paracrine secretion by human CPCs. As a cell-free approach, EVs could circumvent many of the limitations of cell transplantation

Chronic productive cough in young adults is very often due to chronic rhino-sinusitis

Background. Chronic productive cough is a common clinical problem; often potential causes outside the lower respiratory tract are forgotten or ignored. The aim of this study was to make a precise etiopathogenetic diagnosis of chronic productive cough in young adults. Methods. In a clinical setting, 212 subjects (mean age 41±5 years) who had reported chronic productive cough in a previous postal survey of a young adult population underwent within two years clinical and functional investigations following a rational diagnostic approach. Two pulmonologists independently established the diagnosis using a clinically structured interview on nasal and respiratory symptoms, spirometry and other tests when appropriate (bronchodilator test or methacholine bronchial challenge, chest radiography); if rhino-sinusitis was suspected, subjects underwent an ENT examination with nasal endoscopy and/or sinus computed tomography. Results. At the end of the diagnostic procedure, 87 subjects (41%) no longer had chronic productive cough and had normal function. Fifty-eight subjects (27%) had chronic rhino-sinusitis; seventeen subjects (8%) had asthma, and of these fourteen also had chronic rhino-sinusitis; 50 subjects (24%) had COPD stage 0+, of these seven also had chronic rhino-sinusitis. Chronic rhino-sinusitis was more frequent in females than in males (p<0.05). Conclusions. Both in clinical practice and in epidemiological studies, it is important to consider that the origin of chronic productive cough could be frequently outside the lower respiratory tract; a consistent percentage of young adults with persistent productive cough has indeed chronic rhino-sinusitis

Mola : Seminario de Materialidades y Nuevos Paradigmas, Córdoba 2019

Introducción Universo MOLA; Gracias Iván Tarasconi; Materialidades; Diseño de indumentaria. sistema de moldería sin desperdicio: msd. “El mejor residuo es el que no se genera” / Liliana E. Cisneros & Lis Carrizo De La Fuente; La moda en terapia / Paula Aguirre; Nazca objetos. Los desechos plásticos como material de diseño / Josefina Sperat & Paola Cervio; Búsqueda de la materialidad / Andrea de Iacovo; Nuevos Paradigmas; Huella de carbono en la industria de la moda. Medición del impacto personal en vinculación a la industria de la moda y métricas que conducen al cambio de hábitos / Agostina Martino & Isis del Mar Morillas & Natsué Kiyama; Sustentabilidad y diseño ¿Cómo incorporamos criterios sobre la temática en la enseñanza? / Iván Tarasconi & Moriana Abraham; Nuevos paradigmas en la comunicación y el marketing en moda / Gabriela Ratner; Indumento - Cuerpo – Identidad; ¿Sustentabilidad de las formas?: Sistemas de representación del cuerpo en el mundo de la moda / Fabiola Heredia; Moda y género. Una reflexión sobre la percepción de los cuerpos y los vestidos en los vínculos sociales / Victoria Zaccari; Oír al consumidor / Fedra - Silvina Mauricci & Selediana De Souza Godinho & Silvana Golato; Fashion ManifestoEl compromiso hacia el cambio no debe quedar solo en palabras, sino en acciones. El actuar, el dar ejemplo sobre lo que se puede lograr, es lo que en definitiva, va a generar un cambio de consciencia y de paradigmas. Estamos rodeados de información, de letras, de teorías, pero cuando lo materializamos es cuando podemos sentir desde otra dimensión y creer que todo es posible. Universo MOLA está comprometido con el hacer, con el intercambio y con el crecer en colaboración para crear nuevas verdades. Los textos que este documento recolecta no son meras palabras al viento, son acciones evidenciadas en papel que hablan de historias, puntos de vista y especialmente, hilos para seguir tejiendo la construcción de una industria y un consumo responsable de moda en América Latina. Nos enorgullece que Córdoba, una provincia tan rica en creatividad y empeño, sea la abanderada en crear un documento empapado de revolución, de cambio y, primordialmente, de esperanza. La moda, un eje económico y de desarrollo, que a hoy ya sale de la frivolidad y superficialidad, crea oportunidades transversales en todo nuestro sistema de colaboración y crecimiento en sociedad. Entender que es un espacio, altamente creativo, y además de generación de impacto en todas las áreas de nuestra vida, nos llevará a entender su poder e influencia para que todo lo que realicemos dentro de esta industria esté validada por un propósito mayor que sobrepasa todas las aristas del egoísmo. Esta publicación recupera y pone en valor las investigaciones y ponencias presentadas en el primer seminario de materialidades y nuevos paradigmas realizado en la ciudad de Córdoba, junto a la Facultad de Arquitectura, Urbanismo y Diseño de la Universidad Nacional de Córdoba. Este evento ha sido organizado por las Voces del Universo MOLA de Argentina y abrió las puertas para que una comunidad conociera, compartiera y aprendiera sobre estas temáticas que hacen al corazón de la sostenibilidad. Queda en este documento, el eterno agradecimiento a aquellos investigadores, organizaciones, actores y activistas que aportan sus conocimientos todos los días para que entre todos, creemos el mundo justo y ético que buscamos. Que este documento sea fuente de inspiración, conocimiento y punta de pensamiento para todos los que lo lean.Fil: Abraham, Moriana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Tarasconi, Iván. Universidad Nacional de Río Cuarto. Facultad de Ciencias Económicas; ArgentinaFil: Heredia, Fabiola. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Museo de Antropología; ArgentinaFil: Ratner, Gabriela. Universidad de Palermo. Facultad de Diseño y Comunicación; ArgentinaFil: Aguirre, Paula. Fashion Revolution; ArgentinaFil: Sperat, Josefina. Nazca Objetos; ArgentinaFil: Cervio, Paola. Nazca Objetos; ArgentinaFil: De Iacovo, Andrea. Boomara vegan shoes; ArgentinaFil: Martino, Agostina. Iwela Design; ArgentinaFil: Morillas, Isis del Mar. Universidad Siglo 21; ArgentinaFil: Kiyama, Natsué. Universidad Siglo 21; ArgentinaFil: Zaccari, Victoria. Universidad de Morón; Argentin

Exosomal Expression of CXCR4 Targets Cardioprotective Vesicles to Myocardial Infarction and Improves Outcome after Systemic Administration.

Cell therapy has been evaluated to enhance heart function after injury. Delivered cells mostly act via paracrine mechanisms, including secreted growth factors, cytokines, and vesicles, such as exosomes (Exo). Intramyocardial injection of cardiac-resident progenitor cells (CPC)-derived Exo reduced scarring and improved cardiac function after myocardial infarction in rats. Here, we explore a clinically relevant approach to enhance the homing process to cardiomyocytes (CM), which is crucial for therapeutic efficacy upon systemic delivery of Exo. By overexpressing exosomal CXCR4, we increased the efficacy of plasmatic injection of cardioprotective Exo-CPC by increasing their bioavailability to ischemic hearts. Intravenous injection of Exo <sup>CXCR4</sup> significantly reduced infarct size and improved left ventricle ejection fraction at 4 weeks compared to Exo <sup>CTRL</sup> (p < 0.01). Hemodynamic measurements showed that Exo <sup>CXCR4</sup> improved dp/dt min, as compared to Exo <sup>CTRL</sup> and PBS group. In vitro, Exo <sup>CXCR4</sup> was more bioactive than Exo <sup>CTRL</sup> in preventing CM death. This in vitro effect was independent from SDF-1α, as shown by using AMD3100 as specific CXCR4 antagonist. We showed, for the first time, that systemic administration of Exo derived from CXCR4-overexpressing CPC improves heart function in a rat model of ischemia reperfusion injury These data represent a substantial step toward clinical application of Exo-based therapeutics in cardiovascular disease

A Ks-band-selected catalogue of objects in the ALHAMBRA survey

Large scale structure and cosmolog

Cooking pots, tableware, and the changing sounds of sociability in Italy, 1300–1700

This article considers how the sounds produced by the preparation and consumption of meals in Italy changed between around 1300 and 1700. It argues that by focusing on sound, and by using ecological approaches, we can rediscover obscured connections between different categories of material objects. By examining material and textual evidence for three categories of objects associated with cooking and dining – metalwork, ceramics, and glass – the article traces changes in the material cultures of kitchen and table, and the clear impact these changes had on domestic soundscapes. It considers these sound-producing objects as agents of social interaction, exploring the social relationships they constructed, and the role sound played in those relationships. The article then focuses on the practices of cooking and dining, and the way they shaped the sound of objects. Finally, the article situates objects and social practices within the spatial context of the home, tracing an increasing impetus to manage and control specific types of sound in relation to gender. In the discourse on hospitality, noise came to signify a badly-managed, and therefore morally dubious, household, while silence testified to decorous and authoritative domestic management

Mesenchymal stem cell therapy for heart disease.

Mesenchymal stem cells (MSC) are adult stem cells with capacity for self-renewal and multi-lineage differentiation. Initially described in bone marrow, MSC are also present in other organs and tissues. From a therapeutic perspective, facilitated by the ease of preparation and immunologic privilege, MSC are emerging as an extremely promising therapeutic agent for tissue regeneration and repair. Studies in animal models of myocardial infarction have demonstrated the ability of transplanted MSC to engraft and differentiate into cardiomyocytes and vasculature cells. Most importantly, engrafted MSC secrete a wide array of soluble factors that mediate beneficial paracrine effects and greatly contribute to cardiac repair. Together, these properties can be harnessed to both prevent and reverse remodeling in the ischemically injured ventricle. In proof-of-concept and phase I clinical trials, MSC therapy improved left ventricular function, induced reverse remodeling, and decreased scar size. This chapter reviews the current understanding of MSC biology and mechanism of action in cardiac repair of MSC therapy for cardiac disease