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.
O objetivo deste estudo foi analisar fatores associados aos óbitos por COVID-19 em gestantes brasileiras. Trata-se de um transversal, com 7296 gestantes brasileiras com diagnóstico de COVID-19 no ano de 2021. Os dados foram coletados do sistema de informação em saúde OPEN DATASUS. O desfecho estudado foi óbito, e as covariáveis foram referentes a questões sociodemográficas e epidemiológicas. Foi realizada análise de regressão logística, com estimativa de odds ratio (OR) e seus respectivos intervalos de confiança de 95% (IC95%), com nível de significância de 5%. Os fatores associados ao óbito em gestantes foram: residir na região nordeste (OR = 1,37; IC95% 1,03 – 1,82), ter alguma comorbidade (OR = 1,80; IC95% 1,48 – 2,21), internação em UTI (OR = 2,56; IC95% 1,99 – 3,30) e ter feito uso de suporte ventilatório invasivo (OR = 18,73; IC95% 12,89 – 27,21). Deve-se buscar e aplicar serviços de saúde integrais em seus recursos físicos e humanos para uma assistência de qualidade e eficiente com maior atenção ao perfil de gestantes encontrado.
Considering the multifactorial nature of the development of coronary artery calcificatioN (CAD), and the difficulty in making its early diagnosis, this study sought to investigate the role of the TREML4 in the development of atherosclerotic lesions by genotyping of two main variants associated with this gene (rs2803495 and rs2803496), mRNA expression and identification of its regulatory miRNAs. 329 patients with Subclinical atherosclerosis (AS) were recruited. The results with AS patients stratified according to the Duke score demonstrated an association of the Duke score with increased expression of mRNA of the TREML4 in peripheral blood leukocytes (OR. = 3.173, 95% CI = 1.29-7, 78, p = 0.012). Furthermore, genotyping revealed that the SNP genotype combination rs2803495 (AG + GG) (OR = 9,007, 95% CI = 4.1-19.8, p <0.001) and rs2803496 (CT + CC) ( OR = 11.1, 95% CI = 4.8-25.4, p = 0.011), favor the expression of TREML4 mRNA. Patients with AS and carriers of the SNP G alleles rs2803495 (AG + GG) (OR = 13.31, 95% CI = 5, 79-30.61, p <0.001) and C allele rs2803496 (CT + CC) (OR = 18.99, 95% CI = 7.60-47.44, p <0.001) are more likely to express TREML4 . Once again, the C allele was associated with higher levels of mRNA expression (OR = 3.98, 95% CI = 1.67-9.48, p = 0.002). The rs2803495 (AG + GG) and rs2803496 (CT + CC) variants were not related to the development of type 2 Diabetes Mellitus (DM2; p> 0.05). However, patients who express TREML4 and are DM2 have higher levels of expression of TREML4 when compared to the control group (OR = 2.6, 95% CI = 1.19-5.72, p <0.001). Patients with DM2 and rs2803495 (AG + GG) genotypes are more likely to express TREML4 (OR = 20.77, 95% CI = 2.29-188.41, p = 0.007). In silico analyzes showed that 8 miRNAs (hsa-miR-181a-5p, hsa-miR-200b-3p, hsa-miR-24-3p, hsa-miR-296-5p, hsa-miR-361-5p, hsa-miR- 423-5p, hsa-miR-486-3p and hsa-miR-708-5p) are expected to interact with TREML4 mRNA.The results suggest that mRNA expression of the TREML4 is associated with the presence of SNPs and increased in patients with AS with DM2 and that miRNAs may be involved in the regulation of the TREML4 being directly or indirectly involved in the pathophysiology of CVD being potential circulating biomarkers for early detection and/or individualized treatment of AS and CAD.
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