BACKGROUND:The identification of novel biomarkers for early breast cancer detection would be a great advance. Because of their role in tumorigenesis and stability in body fluids, microRNAs (miRNAs) are emerging as a promising diagnostic tool. Our aim was to identify miRNAs deregulated in breast tumors and evaluate the potential of circulating miRNAs in breast cancer detection.

Astroglial cells play an important role in maintaining neuronal function in the adult and in the developing nervous system. Ethanol exposure induces profound alterations in the astrogliogenesis process, affecting important cell functions, including intracellular protein trafficking. Because the actin cytoskeleton plays a crucial role in intracellular protein transport, the aim of the present study was to analyze the effects of ethanol on actin cytoskeleton organization and the involvement of the RhoA signaling pathway in these effects. We show that RhoA and lysophosphatidic acid (LPA), an upstream activator of RhoA, stimulate the formation of stress fibers and focal adhesion in cortical astrocytes in primary culture. Exposure of cultured astrocytes to different concentrations of ethanol profoundly disorganizes the actin cytoskeleton, leading to the formation of actin rings at the cell periphery and decreasing the content of focal adhesion proteins. Furthermore, LPA treatment or RhoA transfection revert the ethanol-induced actin alterations in astrocytes, whereas transfection with an inactive mutant of RhoA is unable to revert the actin ring organization. In addition, inhibition of endogenous RhoA by C3 exoenzyme effectively blocks ethanol-induced actin ring formation. These results suggest that the effects of alcohol on actin cytoskeleton organization are mediated by the RhoA signaling pathway. Disruptions in actin organization may impair important astrocyte functions, participating in ethanol-induced astroglial and brain damage during development.

rather than by caspase-3 cleavage. Accordingly, the RhoA inhibitor C3, completely abolishes the ethanol-induced ROCK-I activation. Furthermore, inhibition of both RhoA and ROCK prevents the membrane blebbing induced by ethanol. Ethanol also promotes myosin light chain (MLC) phosphorylation, which might be involved in the actinmyosin contraction. All of these findings strongly support that ethanol-exposed astrocytes undergo apoptosis by anoikis and also that the RhoA/ROCK-I/MLC pathway participates in this process.

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An increase in the number of older people experiencing disability and dependence is a critical aspect of the demographic change that will emerge within Europe due to the rise in life expectancy. In this scenario, prevention of these conditions is crucial for the well-being of older citizens and for the sustainability of our healthcare systems. Thus, the diagnosis and management of conditions like frailty, which identifies the people at the highest risk for developing those adverse outcomes, is of critical relevance. Currently, assessment of frailty relies primarily on measuring functional parameters, which have limited clinical utility. In this viewpoint article, we describe the FRAILOMIC Initiative, an international, large-scale, multi-endpoint, community- and clinic-based research study funded by the European Commission. The aim of the study is to develop validated measures, comprising both classic and ‘omics-based' laboratory biomarkers, which can predict the risk of frailty, improve the accuracy of its diagnosis in clinical practice and provide a prognostic forecast on the evolution from frailty to disability. The initiative includes eight established cohorts of older adults, encompassing >75,000 subjects, most of whom (∼70%) are aged >65 years. Data on function, nutritional status and exercise habits have been collected, and cardiovascular health has been evaluated at baseline. Subjects will be stratified as ‘non-frail' or ‘frail' using Fried's definition, all adverse outcomes of interest will be recorded and differentially expressed biomarkers associated with the risk of frailty will be identified. Genomic, proteomic and transcriptomic investigations will be carried out using array-based systems. As circulating microRNAs in plasma have been identified in the context of senescence, ageing and age-associated diseases, a miRNome-wide analysis will also be undertaken to identify a miRNA-based signature of frailty. Blood concentrations of secreted proteins known to be upregulated significantly in senescent endothelial cells and other hypothesis-driven biomarkers will be measured using ELISAs. The FRAILOMIC Initiative aims to issue a series of interim scientific reports as key results emerge. Ultimately, it is hoped that this study will contribute to the development of new clinical tools, which may help individuals to enjoy an old age that is healthier and free from disability.