microRNA (miRNA) expression profiles varied greatly among current studies due to different technological platforms and small sample size. Systematic and integrative analysis of published datesets that compared the miRNA expression profiles between hepatocellular carcinoma (HCC) tissue and paired adjacent noncancerous liver tissue was performed to determine candidate HCC associated miRNAs. Moreover, we further validated the confirmed miRNAs in a clinical setting using qRT-PCR and Tumor Cancer Genome Atlas (TCGA) dataset. A miRNA integrated-signature of 5 upregulated and 8 downregulated miRNAs was identified from 26 published datesets in HCC using robust rank aggregation method. qRT-PCR demonstrated that miR-93-5p, miR-224-5p, miR-221-3p and miR-21-5p was increased, whereas the expression of miR-214-3p, miR-199a-3p, miR-195-5p, miR-150-5p and miR-145-5p was decreased in the HCC tissues, which was also validated on TCGA dataset. A miRNA based score using LASSO regression model provided a high accuracy for identifying HCC tissue (AUC = 0.982): HCC risk score = 0.180E_miR-221 + 0.0262E_miR-21 - 0.007E_miR-223 - 0.185E_miR-130a. E_miR-n = Log 2 (expression of microRNA n). Furthermore, expression of 5 miRNAs (miR-222, miR-221, miR-21 miR-214 and miR-130a) correlated with pathological tumor grade. Cox regression analysis showed that miR-21 was related with 3-year survival (hazard ratio [HR]: 1.509, 95%CI: 1.079–2.112, P = 0.016) and 5-year survival (HR: 1.416, 95%CI: 1.057–1.897, P = 0.020). However, none of the deregulated miRNAs was related with microscopic vascular invasion. This study provides a basis for further clinical application of miRNAs in HCC.
The prognostic nomogram provided an individualized risk estimate of short-term survival in patients with ACHBLF, offering to clinicians to improve their abilities to assess patient prognosis.
Background:Non-alcoholic fatty liver disease (NAFLD) is a global health problem affecting more than a quarter of the entire adult population. Both monocytes and high-density lipoprotein cholesterol (HDL-C) were found to participate in the progression of hepatic inflammation and oxidative stress. We speculated that the monocyte-to-HDL-C ratio (MHR) may be associated with the risk of NAFLD.MethodsWe conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018. NAFLD was identified using a controlled attenuation parameter (CAP) of ≥274 dB/m. Degree of liver fibrosis were assessed by liver stiffness measurement (LSM) and LSM values≥8.0, ≥ 9.7, and ≥13.7 kPa were defined as significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4), respectively. The association between MHR and the risk of NAFLD and liver fibrosis was estimated using weighted multivariable logistic regression. The non-linear relationship between MHR and the risk of NAFLD was further described using smooth curve fittings and threshold effect analysis.ResultsOf 4,319 participants, a total of 1,703 (39.4%) participants were diagnosed with NAFLD. After complete adjustment for potential confounders, MHR was positively associated with the risk of NAFLD (OR = 2.87, 95% CI: 1.95–4.22). The risk of NAFLD increased progressively as the MHR quarter increased (P for trend < 0.001). In subgroup analysis stratified by sex, a positive association existed in both sexes; Women displayed higher risk (men: OR = 2.12, 95% CI: 1.33–3.39; women: OR = 2.64, 95%CI: 1.40–4.97). MHR was positively associated with the risk of significant liver fibrosis (OR = 1.60, 95% CI: 1.08–2.37) and cirrhosis (OR = 1.83, 95% CI: 1.08–3.13), but not with advanced liver fibrosis (OR = 1.53, 95% CI: 0.98–2.39) after full adjustment for potential confounders. In the subgroup analysis by sex, the association between MHR and different degrees of liver fibrosis was significantly positive in women. When analyzing the relationship between MHR and NAFLD risk, a reverse U-shaped curve with an inflection point of 0.36 for MHR was found in women.ConclusionHigher MHR was associated with increased odds of NAFLD among Americans of both sexes. However, an association between MHR and liver fibrosis was found mainly among women.
Endotoxin tolerance (ET) is suggested to attenuate the severity of acute liver failure (ALF) in mice, possibly through both innate and adaptive immunity. However, the involvement of regulatory dendritic cells (DCregs) in ET has not been fully elucidated. In this study, their effect on ALF in mice was investigated. Splenic DCregs from ET-exposed mice (ET-DCregs) showed lower expression levels of CD40, CD80, and MHC-II markers and stronger inhibition of allogenic T cells and regulation of IL-10 and IL-12 secretion than splenic DCregs from normal mice (nDCregs). Moreover, the mRNA and protein levels of TNF-α and P65 in splenic ET-DCregs were significantly lower than those in the splenic nDCregs. The survival rate was significantly increased and liver injury was mitigated in mice with ALF treated with splenic ET-DCregs. In addition, A20 expression was decreased in the liver of ALF mice, but elevated after infusion of splenic nDCregs and ET-DCregs, and a much higher elevation was observed after infusing the latter cells. The functionality of splenic DCregs was altered after ET exposure, contributing to protection of the livers against D-GalN/LPS-induced ALF.
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