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Sepsis contributes to the high prevalence of acute kidney injury (AKI), which mainly occurs in hospitalized patients. The delay in AKI detection is a risk factor for death and chronicity; thus, early diagnosis is essential for initiating proper treatment strategies. Although serum creatinine is used as biomarker, it is increased in plasma serum creatinine only at late stages of AKI. MicroRNAs (miRNAs), a class of noncoding RNAs responsible for gene regulation, can be found in biological fluids within vesicles such as exosomes and may be promising tools for the early detection of AKI. We aimed to identify potential blood miRNAs that can be used as early biomarkers of sepsis-induced AKI in rats. Adult male Wistar rats received a single dose of lipopolysaccharide (LPS). The earliest significant increase in serum creatinine was detected 4 h after LPS administration. To evaluate whether miRNAs could act as early biomarkers, blood samples were collected before and 2 h after LPS infusion. Serum NGAL levels were used as a comparative marker. Serum miRNAs were derived from exosomes, and their expression were evaluated by the PCR array. miR-181a-5p and miR-23b-3p showed higher expression in LPS-treated rats than in the control animals (p < 0.05). Bioinformatics analysis showed that both miRNAs target molecules associated with transcription factors that regulate genes related to proinflammatory cytokines. Considering that LPS activates transcription factors that lead to the production of proinflammatory cytokines, possible premature changes in the serum levels of miR-181a-5p and miR-23b-3p may be used to identify sepsis-induced AKI earlier. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.Abbreviations: AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; B2M: beta-2-microglobulin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; LRRC37A2: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1 [ABSTRACT FROM AUTHOR]