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ObjectiveThe study aimed to screen microRNAs (miRNAs) that can be used for the early detection of colorectal cancer (CRC) based on differential expression of miRNA in serum.Materials and methodsA three-stage study was designed with a total of 217 CRCs, 168 colorectal adenomas (CRAs), and 190 healthy controls (HCs). A quantitative reverse transcription polymerase chain reaction was performed in three stages. We screened 528 miRNA expression profiles in the sera of 40 patients (CRC n=20, CRA n=10, and HC n=10) for candidate miRNAs, then 210 serum samples (CRC n=90, CRA n=60, and HC n=60) were used for screening of candidate miRNAs. Three hundred and twenty-five independent individual samples (CRC n=107, CRA n=98, and HC n=120) were used to validate the most differentially-expressed miRNAs in the screening stage, and binary logistic regression was used in the validation stage. A receiver operating characteristic curve was drawn to evaluate the diagnostic accuracy.ResultsA 5-serum miRNA panel (miRNA-1246, miRNA-202-3p, miRNA-21-3p, miRNA-1229-3p, and miRNA-532-3p) effectively distinguished CRCs from HCs with 91.6% sensitivity and 91.7% specificity. The area under the curve (AUC) was 0.960 (95% confidence interval [CI]: 0.937–0.983). In addition, the panel also accurately distinguished CRCs from CRAs with 94.4% sensitivity and 84.7% specificity. The AUC was 0.951 (95% CI: 0.922–0.980).ConclusionOur 5-serum miRNA panel accurately distinguished CRCs from CRAs and HCs with high sensitivity and specificity. The 5-serum miRNA panel may be a promising prospect for application as a nonintrusive and inexpensive method for the early detection of CRC.

Non-esterified fatty acids (NEFAs) promote de novo lipogenesis, which caused abnormal hepatic lipid accumulation, by the NFκB–Orai1 pathway. Oxidative stress and endoplasmic reticulum (ER) stress have been recognized as key mechanisms in non-alcoholic fatty liver disease (NAFLD) pathogenesis. Whether Orai1 facilitates ER stress by oxidative stress remains unknown. The rat model of NAFLD was constructed by feeding high-fat diet (HFD). BRL-3A cells were treated with NEFAs, Orai1inhibtor BTP2, NFκB inhibitor wogonin, or small interfering Orai (siOrai) 1, respectively. The content of intracellular reduced glutathione (GSH) and malondialdehyde (MDA), indicating oxidative stress, was measured by a spectrophotometer. ER stress major proteins PERK, IRE1, ATF6, CHOP, and GRP78 were quantified using Western blot and qRT-PCR analyses. For the intracellular location of reactive oxygen species (ROS) and Orai1 were measured by Western blot and immunofluorescence, and cytosolic Ca2+ was measured by flow cytometry. As we expected, the liver of rats with NAFLD showed lipid droplets in HE and Oil Red O. The decreased GSH and increased MDA were found in rats fed with HFD. ER stress major proteins PERK, IRE1, ATF6, GRP78, and CHOP were significantly increased in the HFD group. In BRL-3A cells, GSH content dramatically decreased from 1 h, MDA content dramatically increased from 3 h, and expression levels of ER stress significantly increased from 3 h by NEFA treatment. Furthermore, cytosolic Ca2+ increased from 0.5 h by NEFAs treated in BRL-3A cells. It indicated that NEFAs increased cytosolic Ca2+ to induce oxidative stress, thus ER stress. The content of oxidative stress and ER stress proteins showed the same trends by NEFAs treated in BRL-3A cells. These effects were reversed by the Orai1 inhibitor BTP2 and the NFκB inhibitor wogonin. Moreover, siOrai1 abrogated NEFAs’ influence in BRL-3A cells. Last, ROS was found by NEFAs treated in BRL-3A cells, and NEFA treatment enhanced the nuclear localization of NF-κB p65 and ORAI1. It was considered that high NEFAs increased cytosolic Ca2+ and enhanced NFκB-dependent SOCE and its moiety protein Orai1 to decrease GSH and thus induced oxidative stress at earlier stages and furthermore tempted ER stress in the pathologic progress of NAFLD.

Cardiopulmonary bypass (CPB) constitutes one of the primary methodologies pertaining to cardiac surgery. However, this form of surgery can cause damage to the body. Many studies have reported that dexmedetomidine confers cerebral protection. In this study, we aimed to investigate the effect and mechanism of dexmedetomidine on neuronal apoptosis caused by CPB. Here, rats were treated with different doses of dexmedetomidine by intravenous infusion 2 hours after CPB. We observed that dexmedetomidine treatment to rats reduces the S100β, NSE levels in plasma, and neuronal apoptosis following CPB in a dose-dependent manner. Furthermore, we observed that the beneficial effect of dexmedetomidine treatment following CPB was associated with a reduction in IL6, an inflammatory cytokine in plasma and cortex. Our results suggest that dexmedetomidine provides neuroprotective effects by inhibiting inflammation and reducing neuronal apoptosis. There was a correlation between the protective effect on the brain and the dose of dexmedetomidine. In addition, dexmedetomidine administration inhibits phosphorylation of JAK2 and STAT3 proteins in the hippocampus of rats 2 hours after CPB. Therefore, we speculate that the JAK2–STAT3 pathway plays an important role in the neuroprotective effects of dexmedetomidine following brain injury induced by CPB.