The miRNAs had different expression profiles dependent on the AF condition, with higher expression in the acute new-onset AF than well-controlled AF. Clinically, this may contribute to an effective assessment for patients, leading to early detection of AF and monitoring to reduce the risk of other serious cardiovascular events.
Clopidogrel is an essential antiplatelet drug used to prevent thrombosis complications associated with atherosclerosis. However, hepatotoxicity is a potential adverse effect related to clopidogrel therapy. Exosome-derived miRNAs may be useful for improved monitoring of drug response and hepatotoxicity risk. In the present study, the expression of several exosomal miRNAs (miR-26a-5p, miR-145-5p, miR-15b-5p, and miR-4701-3p) and cell-derived mRNA targets (PLOD2, SENP5, EIF4G2, HMGA2, STRADB, and TLK1) were evaluated in HepG2 cells treated with clopidogrel (6.25, 12.5, 25, 50, and 100 μM) for 24 and 48 h. Then, clopidogrel cytotoxicity was evaluated by analyzing DNA fragmentation and the cell cycle profile using flow cytometry. Differential expression of exosome-derived miRNAs and cell-derived mRNAs was analyzed by RT-qPCR. Exposure of HepG2 cells to high concentrations of clopidogrel (50 and 100 μM) for 24 h caused significant DNA fragmentation (17.6 and 44.4%, respectively; p < 0.05) and 48 h (26.8 and 48.9%, respectively; p < 0.05), indicating cellular toxicity. Upregulation of miR-26a-5p and downregulation of miR-15b-5p was observed in cells exposed to 100 μM clopidogrel for 24 and 48 h. The miR-26a-5p target mRNAs HMGA2, EIF4G2, STRADB, and SENP5 were downregulated in HepG2 cells following exposure to cytotoxic concentrations of clopidogrel (50 and 100 μM) for 24 h, and HMGA2 levels remained low after 48 h of treatment. TLK1, a target of miR-15b-5p, was downregulated by 50 and 100 μM clopidogrel at 24 h. In conclusion, our results suggest that exposure to high concentrations of clopidogrel modulates the expression of exosomal miR-26a-5p and miR-15b-5p and their target mRNAs in HepG2 cells. Dysregulation of these miRNAs maybe modulate the regulatory pathways involved in clopidogrel-induced liver injury.
Sterol and fatty acid biomarkers and isotopic composition (δ13C and δ15N) of bulk organic matter (OM) were quantified in a sediment core to characterize the accumulation of autochthonous OM in an area on the continental shelf adjacent to Rio de Janeiro State. In the sediment surface (0-1 cm) the concentration of total sterols and fatty acids was at least one order of magnitude higher than that measured deeper down in the core and was dominated by labile and planktonic-derived biomarker compounds. These results suggest, as is confirmed by multivariate statistical analysis, the occurrence of an event of enhanced primary production in the water column and efficient export of particles to the bottom. Similar conditions have been observed at Cabo Frio, located 150 km to the north of our study site, during an upwelling event, suggesting that such events may exert a regional influence on primary production on the south-eastern Brazilian continental shelf. Beyond the signatures from this event, the presence of biomarker compounds from vascular plants suggests the additional influence of an outflow from Guanabara Bay at the study site. These results point to the need for further investigation of the relative influence of physical forcings and continental inputs on the biogeochemical processes on the section of the continental shelf considered in the present study.
Marcadores moleculares na classe de lipídios (esterois, ácidos graxos e hidrocarbonetos) e a composição isotópica (δ13C e δ15N) da matéria orgânica bruta foram quantificados em amostras de um testemunho de sedimento para caracterizar o histórico recente de sedimentação da matéria orgânica na plataforma continental adjacente à Baía de Guanabara, no Estado do Rio de Janeiro. Na superfície do sedimento (0-1 cm), a concentração total de esterois e ácidos graxos foi cerca de uma ordem de grandeza maior do que observado nas camadas mais profundas do sedimento, com predominância de lipídios derivados da produção planctônica. Esses resultados sugerem, como confirmado através de estatística multi-variada, a ocorrência de um evento de elevada produção primária na coluna d'água e uma exportação rápida e eficiente das partículas para o sedimento. Condições similares são observadas na região de ressurgência de Cabo Frio, localizada cerca de 150 km ao norte da área de estudo. Portanto, nossos resultados sugerem que tais eventos têm uma influência regional sobre a produção primária na margem continental sudeste do Brasil. Por outro lado, a presença de lipídios derivados de plantas vasculares de origem continental ressalta a necessidade de investigar com maior profundidade a influência relativa entre forçantes físicas e o aporte continental sobre processos biogeoquímicos na porção da plataforma continental considerada no presente trabalho
An integrative analysis of miRNA and mRNA expression profiles in left ventricle (LV) of diabetes-induced rats was performed to elucidate the role of miRNAs and their mRNAs target in diabetic cardiomyopathy (DCM). mRNA (GSE4745) and miRNA (GSE44179) datasets were downloaded from Gene Expression Omnibus 2R (GEO2R) and differentially expressed mRNAs and miRNAs were selected. Cardiotoxicity-related mRNAs (n=7) were analyzed by Ingenuity Pathway Analyses 6 (IPA) and regulatory miRNAs (n=639) were identified using TargetScan 7.1. web dataset. The integrative analysis was performed between miRNAs differentially expressed in GSE44179 and regulatory TargetScan-detected miRNAs of mRNAs differentially expressed in GSE4745. and mRNAs were up-and-down regulated, respectively, in GSE4745 on days 3 and 42 after diabetes-induction. The regulatory miRNAs, rno-miR-877, rno-miR-320 and rno-miR-214 were down-regulated, and regulatory miRNAs, rno-miR-17, rno-miR-187, rno-miR-34a, rno-miR-322, rno-miR-188, rno-miR-532 and rno-miR-21, were up-regulated in GSE44179 dataset. These results are suggestive that and mRNAs and their regulatory miRNAs play a role in DCM pathogenesis and they may be potential circulating biomarkers to detect early cardiovascular complications in diabetic patients.
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