The function and regulation network mechanism of circRNA in liver diseases.

Circular RNA (circRNA), a new type of endogenous non-coding RNA, is abundantly present in eukaryotic cells, and characterized as stable high conservation and tissue specific expression. It has been generated increasing attention because of their close association with the progress of diseases. The liver is the vital organ of humans, while it is prone to acute and chronic diseases due to the influence of multiple pathogenic factors. Moreover, hepatocellular carcinoma (HCC) is the one of most common cancer and the leading cause of cancer death worldwide. Overwhelming evidences indicate that some circRNAs are differentially expressed in liver diseases, such as, HCC, chronic hepatitis B, hepatic steatosis and hepatoblastoma tissues, etc. Additionally, these circRNAs are related to proliferation, invasion, migration, angiogenesis, apoptosis, and metastasis of cell in liver diseases and act as oncogenic agents or suppressors, and linked to clinical manifestations. In this review, we briefly summarize the biogenesis, characterization and biological functions, recent detection and identification technologies of circRNA, and regulation network mechanism of circRNA in liver diseases, and discuss their potential values as biomarkers or therapeutic targets for liver diseases, especially on HCC.

Association Between Environmental and Socioeconomic Risk Factors and Hepatocellular Carcinoma: A Meta-Analysis.

BACKGROUND: The association between environmental and socioeconomic risk factors and the occurrence of hepatocellular carcinoma (HCC) are still inconclusive. A meta-analysis was conducted to address this issue. METHODS: We systematically searched the databases including PubMed, Web of Science, and Google Scholar and collected the related risk factors of HCC before March 6, 2020. Statistical analysis was performed on the odds ratio (OR) value and 95% CI of the correlation between environmental and socioeconomic factors and HCC. Begg's rank correlation test, Egger's linear regression test, and the funnel plot were employed for identification of the publication bias. RESULTS: Out of 42 studies, a total of 57,892 participants were included. Environmental and socioeconomic risk factors including ever educated (illiteracy); race (Black, Hispanic, and Asian); medium and low incomes; occupations (farmer and labor); passive smoking; place of residence (rural); blood aflatoxin B1 (AFB1) adduct level; exposure of pesticide, etc., were statistically increased with the occurrence of HCC (P < 0.05) and OR values and 95% CIs were 1.37 (1.00, 1.89), 2.42 (1.10-5.31), 1.90 (0.87-4.17), 5.36 (0.72-40.14), 1.48 (1.11, 1.96), 1.74 (1.00-3.03), 1.49 (1.06-2.08), 1.52 (1.07-2.18), 1.43 (0.27, 7.51), 1.46 (1.09, 1.96), 2.58 (1.67-3.97), and 1.52 (0.95-2.42), respectively. We found 6-9, 9-12, and ≥12 years of education that statistically reduced the risk of the occurrence of HCC (P < 0.05) and OR values and 95% CIs were 0.70 (0.58, 0.86), 0.52 (0.40, 0.68), and 0.37 (0.23, 0.59), respectively. No significant associations (P > 0.05) were observed between race (Hispanic and Asian), passive smoking, marital status, place of birth, place of residence, and HCC. In stratified analysis, exposure of pesticide was statistically significant (P < 0.05), while race of black was on the contrary. CONCLUSION: Environmental and socioeconomic risk factors have great impacts on the incidence rate of HCC. Improving national education and income levels can significantly reduce the risk of HCC. PROSPERO REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier: CRD42020151710.

Non-linear associations between metabolic syndrome and four typical heavy metals: Data from NHANES 2011-2018.

Previous studies have found that heavy metals are associated with metabolic syndrome (MetS), although findings are inconsistent. Further, investigations into potential associations that consider age- or gender-specific effects and dose-response associations for metal exposure and MetS are rare. In this study, we explore the associations between blood levels of typical heavy metals [lead (Pb), cadmium (Cd), mercury (Hg) and manganese (Mn)] and MetS among adults using logistic regression analysis and restricted cubic splines (RCS) logistic analysis using data from the US National Health and Nutrition Examination Survey 2011-2018. After adjusting for covariates, higher levels of blood Pb, Cd and Hg were associated with lower risks of MetS in participants overall, and in all subgroup analyses, by logistic regression analysis (all P-values <0.05); in contrast, higher levels of blood Mn had a higher risk of MetS only in the age group of 30-49 years (P-values <0.05). We also found non-linear associations of heavy metal levels in blood with risk of MetS in participants overall, in specific age groups and in both genders, using RCS logistic regressions (all P-values <0.05). In addition, the non-linear associations of Pb and Hg we observed in different subgroups differed. In conclusion, blood levels of four heavy metals were associated with the risk of MetS through a variety of non-linear patterns.

The Construction and Analysis of ceRNA Network and Immune Infiltration in Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) has the highest invasion, mortality and metastasis of the renal cell carcinomas and seriously affects patient's quality of life. However, the composition of the immune microenvironment and regulatory mechanisms at transcriptomic level such as ceRNA of KIRC are still unclear. Methods: We constructed a ceRNA network associated with KIRC by analyzing the long non-coding RNA (lncRNA), miRNA and mRNA expression data of 506 tumor tissue samples and 71 normal adjacent tissue samples downloaded from The Cancer Genome Atlas (TCGA) database. In addition, we estimated the proportion of 22 immune cell types in these samples through "The Cell Type Identification by Estimating Relative Subsets of RNA Transcripts." Based on the ceRNA network and immune cells screened by univariate Cox analysis and Lasso regression, two nomograms were constructed to predict the prognosis of patients with KIRC. Receiver operating characteristic curves (ROC) and calibration curves were employed to assess the discrimination and accuracy of the nomograms. Consequently, co-expression analysis was carried out to explore the relationship between each prognostic gene in a Cox proportional hazards regression model of ceRNA and each survival-related immune cell in a Cox proportional hazards regression model of immune cell types to reveal the potential regulatory mechanism. Results: We established a ceRNA network consisting of 12 lncRNAs, 25 miRNAs and 136 mRNAs. Two nomograms containing seven prognostic genes and two immune cells, respectively, were successfully constructed. Both ROC [area under curves (AUCs) of 1, 3, and 5-year survival in the nomogram based on ceRNA network: 0.779, 0.747, and 0.772; AUCs of 1, 3, and 5-year survivals in nomogram based on immune cells: 0.603, 0.642, and 0.607] and calibration curves indicated good accuracy and clinical application value of both models. Through co-correlation analysis between ceRNA and immune cells, we found both LINC00894 and KIAA1324 were positively correlated with follicular helper T (Tfh) cells and negatively correlated with resting mast cells. Conclusion: Based on the ceRNA network and tumor-infiltrating immune cells, we constructed two nomograms to predict the survival of KIRC patients and demonstrated their value in improving the personalized management of KIRC.

Carbon nanotube-mediated antibody-free suspension array for determination of typical endocrine-disrupting chemicals.

A carbon nanotube (CNT)-mediated antibody-free suspension array (CASA) by integration of functionalized CNTs and aptamer (Apt) into xMAP® technology for simultaneous determination of typical endocrine-disrupting chemicals (EDCs) was developed . The interaction between CNTs and Apt acts as an effective and straightforward signal recognition, transformation, and amplification strategy. The amino-functionalized CNTs are covalently modified on the carboxyl-functionalized magnetic bead (MB) and further physically bridging with biotinylated Apt. CNTs on the surface of MBs not only increase the amount of Apt for target binding and signal amplification but also maintain the biological activity of Apt. After magnetic separation, the encoded MB address was distinguished and the concentration of the target in the liquid was negatively correlated with median fluorescence intensity. A series of environmental water samples were analysed by CASA, traditional immuno-SA, and competitive inhibition enzyme-linked immunosorbent assay for validation. The results obtained using CASA well matched for the multiplexed detection of various targets with dynamic concentration range from 6.40 × 10-5 to 4.00 µg L-1 within 1 h. The method also confirmed good selectively, accuracy, and consistency with high-performance liquid chromatography. Graphical abstractSchematic representation of amino-functionalized carbon nanotube (CNT)-bridged antibody-free suspension array for detecting of three typical endocrine-disrupting chemicals. The amino-functionalized CNTs are covalently modified and further physically interacted with biotinylated aptamer featuring in the recognition and binding with the target of interest.