Time-gated luminescence acquisition for biochemical sensing: miRNA detection*Relacionar en OpeAire*

Luminescence emission is a multidimensional phenomenon comprising a time-domain layer defined by its excited-state kinetics and corresponding lifetime, which is specific to each luminophore and depends on environmental conditions. This feature allows for the discrimination of luminescence signals from species with a similar spectral profile but different lifetimes by time-gating (TG) the acquisition of luminescence. This approach represents an efficient tool for removing unwanted, usually short-lived, signals from scattered light and fluorescence interferents using luminophores with a long lifetime. Due to the emergence of time-resolved techniques using rapid excitation and acquisition methods (i.e., pulsed lasers and single-photon timing acquisition) and new long-lifetime luminophores (i.e., acridones, lanthanide complexes, nanoparticles, etc.), TG analyses can be easily applied to relevant chemical and biochemical issues. The successful application of TG to important biomedical topics has attracted the attention of the R&D industry due to its potential in the development and patenting of new probes, methods and techniques for drug discovery, immunoassays, biomarker discovery and biomolecular interactions, etc. Here, we review the technological efforts of innovative companies in the application of TG-based techniques. Among the many currently available biomarkers, circulating microRNAs (miRNAs) have received attention since they are highly specific and sensitive to different pathological stages of numerous diseases and easily accessible from biological fluids. qPCR is a powerful and routine technique used for the detection and quantification of miRNAs, but qPCR may introduce numerous artefacts and low reproducibility during the amplification process, particularly using complex samples. Thus, due to the efficiency of TG in separating short- lived sources of fluorescence common in biological fluids, TG is an ideal approach for the direct detection of miRNAs in liquid biopsies. Recently, great efforts in the use of TG have been achieved. Our contribution is the proposal of a direct detection approach using TG- imagining with single nucleobase resolution.European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 690866 (miRNA-DisEASY)Proyecto CTQ2017-85658-R. Ministerio de Economía y Competitividad/Agencia Estatal deInvestigación/Fondo Europeo de Desarrollo Regional (FEDER

Hepatic microcirculation and mechanisms of portal hypertension.

The liver microcirculatory milieu, mainly composed of liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs) and hepatic macrophages, has an essential role in liver homeostasis, including in preserving hepatocyte function, regulating the vascular tone and controlling inflammation. Liver microcirculatory dysfunction is one of the key mechanisms that promotes the progression of chronic liver disease (also termed cirrhosis) and the development of its major clinical complication, portal hypertension. In the present Review, we describe the current knowledge of liver microcirculatory dysfunction in cirrhotic portal hypertension and appraise the preclinical models used to study the liver circulation. We also provide a comprehensive summary of the promising therapeutic options to target the liver microvasculature in cirrhosis