Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.

Diagnostic value of circRNAs as effective biomarkers in human cardiovascular disease: an updated meta-analysis.

Background: A growing body of literature has demonstrated that circular RNAs (circRNAs) are the potential biomarkers in human cardiovascular disease (CVD). Therefore, a meta-analysis based on current studies was accomplished to appraise the role of circRNAs in the diagnostic of CVD patients. Methods: Studies before October 30, 2021, were searched using PubMed, EMBASE, the Web of Science, and Cochrane Library. The diagnostic odds ratio (DOR) with a confidence interval (CI) of 95% was used to investigate the associations between circRNAs and CVDs. Results: A total of 27 eligible articles were selected, including 47 studies, with 6833 participants meeting the criteria standard constrain. The pooled overall sensitivity and specificity for circRNAs expression profile in differentiating CVD patients from controls (non-CVDs or healthy subjects) were 0.81 (95%CI 0.78-0.83) and 0.74 (95%CI 0.68-0.78), respectively; the overall positive likelihood ratio was 3.1 (95%CI 2.5-3.7); the negative likelihood ratio was 0.26 (95%CI 0.22-0.31); the overall diagnostic odds ratio corresponding to an area under the curve of 0.85 (95%CI 0.81-0.88) was 12 (95%CI 9-16). Subgroup analysis indicated that the serum rather than blood has higher diagnostic accuracy. Likewise, meta-regression analysis demonstrated that the specimen, detection method, sample size, and publication year were the main sources of heterogeneity. Sensitivity analysis and Deeks' funnel plot revealed that our results are relatively robust. Conclusions: Our evidence-based analysis results suggested that circRNAs provide higher diagnostic accuracy in the prediction of CVDs. Thus, circRNAs might be potential biomarkers in CVDs.

Expression of the circular RNAs in astaxanthin promotes cholesterol efflux from THP-1 cells based on RNA-seq.

BACKGROUND: It is reported that circular RNAs (circRNAs) play a key role in atherosclerosis (AS). Foam cell formation, which is the main feature of AS, can be significantly inhibited by cholesterol efflux. METHODS: We established a model of astaxanthin (AST) promoting cholesterol efflux from macrophages through oil red O staining, real-time quantitative PCR (qRT-PCR), and western blot and used RNA sequencing to detect the expression of circRNAs in AST-treated and untreated THP-1 cells. Finally, siRNA transfection screened out circRNAs that were significantly differentially expressed. The data analysis was performed by Student's t test and P < 0.05 was considered statistically significant. RESULTS: In the model of AST promoting cholesterol efflux from THP-1 cells, there were a total of 7276 circRNAs differentially expressed, among which the top 25 upregulated and the top 25 downregulated circRNAs were selected based on the log2 (fold change). GO analysis showed that differential expression of circRNAs in biological process (2066/3098; 66.69%), molecular function (543/3098; 17.53%), and cellular component (489/3098; 15.78%). Based on KEGG analysis, RNA transport was the most enriched pathway. Finally, we obtained 3 significantly upregulated circRNAs by siRNA transfection and qRT-PCR. CONCLUSIONS: The 3 differentially expressed circRNAs may play an important role in the process of AST promoting cholesterol efflux and may be used as biomarkers to prevent AS.

The potential diagnostic value of extracellular vesicle miRNA for human non-small cell lung cancer: a systematic review and meta-analysis.

Background: This meta-analysis aimed to evaluate the diagnostic accuracy of extracellular vesicles (EV) miRNAs for non-small cell lung cancer (NSCLC).Methods: All eligible studies were searched in an online database. Stata 15.0, Meta-disc 14.0 and Review Manager 5.2 software packages were used to perform all statistical analysis.Results: The analysis included 16 articles and 70 studies. Pooled sensitivity (SEN) and specificity (SPE), positive predictive value and negative predictive value were 0.77 (95% CI: 0.72-0.80), 0.83 (95% CI: 0.78-0.86), 0.88 (95% CI: 0.86-0.90) and 0.63 (95% CI: 0.58-0.68), respectively. The overall diagnostic odds ratio (DOR) was 16 (95% CI: 11-21) and the area under the curve (AUC) was 0.86 (95% CI: 0.83-0.89). 3 EV miRNAs could identify metastatic NSCLC from healthy, and 10 distinguish early-stage NSCLC. The respective targets of EV miR-21, miR-210, and miR-1290 could activate PI3K/AKT-related pathway.Conclusion: EV miRNAs had high diagnostic accuracy (AUC = 0.86) for NSCLC, especially metastatic NSCLC (AUC = 0.90), and early-stage NSCLC (AUC = 0.88). Besides, multitudinous EV miRNAs combined showed higher diagnostic value than alone. EV miR-21, miR-210, and miR-1290 might be associated with PI3K/AKT-related pathway and the valuable diagnostic biomarkers for NSCLC.

The prognostic significance of long non-coding RNAs in hepatocellular carcinoma: An updated meta-analysis.

BACKGROUND: Recently, many studies have demonstrated that long non-coding RNAs (lncRNAs) are abnormally expressed in hepatocellular carcinoma (HCC) and may serve as a potential molecular biomarker to evaluate the prognosis of hepatocellular carcinoma. Therefore, we accomplished a meta-analysis built on current studies to assess the prognostic value of lncRNAs in hepatocellular carcinoma. METHODS: The PubMed database was carefully searched to collect all eligible studies until February 20, 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of the overall survival, relapse-free survival, and progression-free survival were calculated to evaluate the prognostic significance of lncRNAs expression in hepatocellular carcinoma using Stata12.0 software. Heterogeneity, sensitivity analysis, and publication bias were also evaluated. RESULTS: The results showed that the expression level of lncRNAs was significantly correlated with clinical outcomes. Abnormally expressed lncRNAs predicted poor overall survival (HR=2.19, 95% CI: 1.99-2.42, P<0.001; I2=44.7%, P=0.005), relapse-free survival (HR=2.68, 95% CI: 1.74-4.14, P<0.001; I2=0.0%, P=0.763) and progression-free survival of hepatocellular carcinoma patients (HR=2.44, 95% CI: 1.53-3.89, P<0.001; I2=0.0%, P=0.336). Statistical significance was also noted in subgroup meta-analyses that were stratified by follow-up time, cutoff value, and quality score. Moreover, the pooled results indicated that lncRNAs expression was significantly associated with tumor size (HR=1.48, 95% CI: 1.24-1.79), tumor number (HR=1.34, 95% CI: 1.08-1.66), and tumor node metastasis stage (HR=2.10, 95% CI: 1.48-2.99), but not liver cirrhosis and tumor differentiation (P>0.05). CONCLUSIONS: This meta-analysis indicates that lncRNAs are strongly associated with prognosis in hepatocellular carcinoma and may serve as a promising indicator for prognostic evaluation of patients with hepatocellular carcinoma. But larger clinical studies are needed to verify its feasibility.

You did not mean it: Perceived good intentions alleviate sense of unfairness.

Previous research has reported that feedback-related negativity (FRN) may represent the degree of perceived unfairness in the ultimatum game (UG). However, few studies have incorporated intention-related consideration in examining the neural correlates of fairness perception. To address this issue, the present study introduced an intentional UG paradigm to disentangle the effect of perceived intention from fairness concerns, using an event-related potential (ERP) analysis. Consistent with the hypothesis, the behavioral results indicated that good intention could markedly reduce rejection rates, and this intention effect was modulated by the degree of fairness, which was more prominent under unfair scenarios. Further electrophysiological results showed that, for the unfair division schemes, FRN and P300 amplitudes were significantly different between offers proposed with good intention and those with bad intention, while such discrepancies were not observed for the fair condition. In summary, converging results demonstrated that perceived intention can modulate the effect of fairness in social decision-making.