Análisis de los microRNA en enfermedades cardiovasculares y envejecimiento cardiaco

Cardiovascular diseases (CVD) are one of the main causes of death that affect worldwide. Thereare several risk factors for the development of CVD, among them, aging is important, whichimplies the anatomical and functional deterioration of the heart. CVD constitute a great burdenin advanced societies. There is a need for the development of therapies and non-invasiveprognostic and diagnostic biomarkers to effectively tackle them. microRNAs (miRNAs) are smallRNAs known to regulate main biological process. For this reason, miRNAs have been proposedas a powerful therapeutic targets or biomarkers.Here the role of miRNAs in the development of CVD and cardiac aging has been reviewed. Inaddition, the translation level of results in animal models to human has been investigated. Asresult, a complete compilation of miRNAs that contribute to CVD and cardiac aging is offered.This literature compilation points out that the great majority of the described miRNAs remainunstudied in human. Based in the high degree of miRNA sequence conservation between speciesand their target sequences, similar functions could be expected in human. Yet, otherphysiological differences in comparison with animal models could suggest the contrary. Toassess the contribution of miRNA in cardiac related pathophysiology, cardiomyocytes derivedfrom human induced pluripotent stem cells (iPSC-CMs) emerge as a model for their studyavoiding this translation difficulties.In addition, the BSICoS group has built a bioinformatic regulatory network controlled by miRNAsassociated with biological age (BIO-AGEmiRNAs) of the human myocardium. Experimentalvalidation of the interactions within this network is required. A new cost-effective validation toolhas been built using fluorescence. Last, luciferase reporter assays (DualGlo assay) are used tostudy interaction of cardiac-related genes with miR-3916. As a result, positive interaction trendshave been observed for CASQ2, ACTN2 and DSP with miR-3916. This fact highlights the potentialof miRNAs in the regulation of genes associated with human cardiac aging and CVD and theirpowerful value as therapeutic targets.<br /

Desarrollo de nanotransportadores de DNA de vanguardia con capacidad cardioregenerativa utilizando el potencial terapéutico de los microRNAs

El infarto de miocardio, si no es mortal, conduce a un remodelado del tejido cardíaco que evoluciona hacia la insuficiencia cardíaca puesto que el corazón carece de capacidad regenerativa. Actualmente no existe una terapia regenerativa, pero se han descrito microRNAs (miR), por ejemplo, el miR-199a-3p, que la promueven a través de la estimulación la proliferación de cardiomiocitos. En este trabajo se han desarrollado y caracterizado nanoestructuras de DNA (DNS) capaces de transportar el miR-199a-3p, internalizarse de manera eficiente en la célula y liberar el miR de manera funcional utilizando la propia maquinaria de la célula. Este trabajo sienta las bases para futuros desarrollos de la terapia cardioregenerativa basada en miR

Terapias cardiacas avanzadas con microRNAs basadas en nanoestructuras de DNA

La desregulación de microRNAs (miRNAs) se asocia con múltiples procesos incluidos el envejecimiento cardiaco y las enfermedades cardiovasculares (ECV). Por ello, se posicionan como prometedoras dianas terapéuticas. Para superar limitaciones en su uso como tal, se propone la creación de nanoestructuras de DNA (DNS) biocompatibles para crear terapias efectivas y seguras

Exploring shRNA-based therapy to prevent chemotherapy-induced cardiotoxicity

Chemotherapy-induced cardiotoxicity is an often fatal consequence of some cancer treatments, such as anthracyclines like doxorubicin (DOXO), for which there is currently no preventive treatment. Since the cardiotoxic mechanism of DOXO is due to its action on topoisomerase 2 β (TOP2B), some studies have described the protective effects of its cardiomyocyte-specific inhibition. In this work we have develop and characterized an RNA interference (RNAi) strategy to inhibit TOP2B. Although our preliminary results show low inhibition of TOP2B in vitro, they encourage future development of more efficient shRNAs

Cardiomiocitos derivados de células pluripotentes inducidas (hiPSC-CM) con progerina inducible para estudiar envejecimiento cardiaco

Molecular bases of cardiac aging still remain in the dark. Though hiPSC-CM are a usefull tool to study mechanisms, they present an immature phenotype. here, we present a maturation strategy and defind the progerin induction contitions for further aging analyisis&nbsp;in vitro.Las bases moleculares del envejecimiento cardiaco no se conocen en profundidad. Los hiPSC-CM son una herramienta útil para este tipo de estudios, pero presentan un fenotipo inmaduro. En este estudio, proponemos una estrategia de maduración y definimos las condiciones de inducción de progerina para el posterior estudio del envejecimiento in vitro

microRNAs en envejecimiento cardiaco humano: dianas terapéuticas y biomarcadores

Cardiovascular diseases (CVD) are the leading cause of death globally, being age one of the most important predisposing risk factor. MicroRNAs (miRNAs) are key post-transcriptional regulators of multiple biological processes, including cardiac aging. MiRNAs are nowadays emerging therapeutics. Also, miRNAs are cutting-edge biomarkers, as they can be actively or passively released from tissues to body fluids (i.e. blood) acting as indicators of physiological and pathophysiological processes in tissues. However, the role of miRNAs in age-related cardiac remodelling is poorly understood in humans. This limits their use as anti-aging interventions, to reduce the risk of CVD, but also as biomarkers of the true physiological state of the heart in relation to age (biological age indicators). Our group recently described the miRNome dynamics with age, chronological and biological, of the human left ventricle. We identified a number of miRNAs related to biological age (BIO-AGEmiRNAs) and bioinformatically established their downstream gene regulation network. Also, a number of cardiac-enriched BIO-AGEmiRNAs were described. Here, we aim to validate the BIO-AGEmiRNA regulatory network and to describe miRNA indicators of the biological age of the heart.Las enfermedades cardiovasculares (ECV) son la principal causa de muerte globalmentem siendo la edad uno de los factores de riesgo más importantes. Los microRNA(miRNA) son reguladores postranscripcionales clave de múltiples procesos biológicos, entre ellos el envejecimiento cardíaco. Los miRNA son hoy en día dianas terapéuticas emergente. Además, los miRNA son biomarcadores de vanguardia, ya que pueden ser liberados activa o pasiva de los tejidos a los fluidos corporales (es decir, la sangre) actuando como indicadores de procesos fisiológicos y fisiopatológicos en los tejidos. Sin embargo, el papel de los miRNA en la remodelación cardiaca relacionada con la edad esta escasamente estudiado en humanos. Esto limita su uso como intervenciones antienvejecimiento, para reducir el riesgo de ECV, pero también como biomarcadores del verdadero estado fisiológico del corazón en relación con la edad (indicadores de edad biológica). Nuestro grupo ha descrito recientemente la dinámica de expresión de los miRNAs con la edad, cronológica y biológica, del ventrículo izquierdo humano. Identificamos una serie de miRNAs relacionados con la edad biológica (BIO-AGEmiRNAs) y establecimos bioinformáticamente su red de regulación génica. Asimismo, se describió una serie de BIO-AGEmiRNAs enriquecidos en el corazón. Nuestro objetivo es validar la red reguladora BIO-AGEmiRNA y describir los miRNA indicadores de la edad biológica del corazón. &nbsp

Envejecimiento cardiaco humano: transcriptómica y desarrollo de modelos celulares de envejecimiento

Pese a la relevancia de la edad como factor de riesgo de las enfermedades cardiovasculares, sus bases moleculares y funcionales están poco caracterizadas en humanos. Para mejorar esta comprensión hemos estudiado su dinámica transcripcional cronológica y biológica en ventrículo izquierdo humano y hemos desarrollado un modelo de envejecimiento celular cardiaco

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America : the ESTAMPA screening study protocol

Q1Q1Introduction Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. Methods and analysis Women aged 30–64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. Ethics and dissemination The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. Trial registration number NCT01881659Revista Internacional - Indexad

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good