Association of Dietary and Supplement Intake of Antioxidants with Risk of Dementia: A Meta-Analysis of Cohort Studies.

BACKGROUND: Dementia is a neuropsychiatric disorder with cognitive decline due to multiple factors. With the arrival of the aging population, the incidence of dementia has gradually increased. There is still no effective treatment for dementia, and therefore, the prevention of dementia has become crucial. Oxidative stress is considered to be one of the pathogenesis of dementia; therefore, antioxidant therapy and prevention of dementia have been gradually proposed. OBJECTIVE: Our meta-analysis aimed to investigate the association of antioxidants with risk of dementia. METHODS: We searched PubMed, Embase, and Web of Science databases for articles on antioxidants associated with dementia risk, and those containing cohort studies with high-dose versus low-dose controls were included in our meta-analysis. The resulting risk ratios (RR) and hazard ratios (HR) and 95% confidence intervals were statistically analyzed using Stata12.0 free software. RESULTS: A total of 17 articles were included in this meta-analysis. Of 98,264 participants, 7,425 had dementia after 3-23 years of follow-up. The results of the meta-analysis showed a trend towards a lower incidence of dementia with high intake of antioxidants (RR = 0.84, 95% CI 0.77-1.19 I2 = 54.6%), but this was not statistically significant. High antioxidant intake significantly reduced the incidence of Alzheimer 's disease (RR = 0.85, 95% CI 0.79-0.92 I2 = 45.5%), and we additionally carried out subgroup analyses by nutrient type, diet or supplement, region, and study quality score. CONCLUSION: Dietary intake of antioxidants or supplements reduces both the risk of dementia and the risk of Alzheimer's disease.

Circular RNA-UBE2D2 accelerates the proliferation and metastasis of non-small cell lung cancer cells via modulating microRNA-376a-3p/Eukaryotic Translation Initiation Factor 4γ2 axis.

Non-small cell lung cancer (NSCLC) ranks first in the morbidity and mortality of malignant tumors in China. As reported, circular RNAs (circRNAs) are emerged in the progress of NSCLC. The study was to figure out the potential mechanism of circ-UBE2D2 in the progression of NSCLC. First, plasmid vectors intervening circ-UBE2D2, microRNA (miR)-376a-3p or Eukaryotic Translation Initiation Factor 4γ2 (EIF4G2) expression were transfected into NSCLC cells, and the expression of circ-UBE2D2, miR-376a-3p and EIF4G2 was detected by reverse transcription quantitative polymerase chain reaction or Western blot. Then, cell proliferation was detected by Cell counting kit-8 assay and plate cloning. Cell apoptosis was tested by flow cytometry. Plate scratches and Transwell were used to detect cell migration and invasion. Finally, the binding sites of circRNA UBE2D2, EIF4G2 and miR-376a-3p were verified by bioinformatics website starBase analysis and dual luciferase reporter gene assay. The results manifested the up-regulation of circ-UBE2D2 expression in NSCLC tissues and cells. Circ-UBE2D2 promoted the proliferation, migration and invasion, but repressed apoptosis of NSCLC cells. Interestingly, circ-UBE2D2 directly targeted miR-376a-3p and up-regulated miR-376a-3p restrained proliferation, migration and invasion, but accelerated apoptosis of NSCLC cells. More importantly, EIF4G2 was the target of miR-376a-3p, and overexpression of EIF4G2 reversed the effects of circ-UBE2D2 downregulation on proliferation, migration, invasion and apoptosis of NSCLC cells. These results suggest that circ-UBE2D2 promotes the proliferation, migration and invasion but restrains apoptosis of lung cancer cells by regulating miR-376a-3p/EIF4G2 axis.

TRIM59 as a novel molecular biomarker to predict the prognosis of patients with NSCLC.

As a member of the tripartite motif family, tripartite motif-containing protein 59 (TRIM59) serves as an E3 ubiquitin ligase in various cellular processes, including intracellular signaling, development, apoptosis, protein quality control, innate immunity, autophagy and carcinogenesis. The present study aimed to investigate the expression and prognostic value of TRIM59 in patients with non-small cell lung cancer (NSCLC). Expression of TRIM59 in patients with NSCLC was measured by immunohistochemistry in tissue microarrays. Datasets from The Cancer Genome Atlas (TCGA) were used to further verify the expression level of TRIM59 in NSCLC, lung adenocarcinoma and lung squamous cell carcinoma (LUSC). The prognostic value of TRIM59 in NSCLC was also analyzed. Immunohistochemistry revealed that TRIM59 was primarily located in the cytoplasm of tumor cells. Analysis of TCGA datasets revealed that TRIM59 was more highly expressed in tumor tissues than in normal tissues (P<0.0001). Furthermore, the TRIM59 expression level was associated with tumor differentiation (P=0.012), while no association was observed between TRIM59 expression and any other clinicopathological parameters. However, the average overall survival rate of patients with NSCLC in the high TRIM59 expression group was significantly lower than that in the low expression group (P=0.014), especially in patients with LUSC (P=0.016) and patients with poor differentiation (P=0.033). The multivariate analysis indicated that high TRIM59 expression is an independent prognostic factor in patients with NSCLC (P=0.018) and was associated with poor prognosis in patients with NSCLC. Therefore, TRIM59 may serve as a novel molecular biomarker to predict the prognosis of patients with NSCLC.

ARHGAP30 suppressed lung cancer cell proliferation, migration, and invasion through inhibition of the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Rho GTPase-activating protein 30 (ARHGAP30), a member of the Rho GTPase-activating proteins (Rho GAPs) family, plays an important role in the regulation of cytoskeleton organization and cell adhesion. MATERIALS AND METHODS: mRNA and protein expression was assessed by quantitative real-time PCR and Western blotting, respectively. Cell Counting Kit-8 (CCK-8) and Transwell assays were conducted to detect cell proliferation, migration, and invasion. RESULTS: ARHGAP30 expression was downregulated in specimens and cell lines of lung cancer in comparison to non-cancerous specimens and normal bronchial epithelial cell lines, respectively. Moreover, in vitro experiments demonstrated that ARHGAP30 overexpression impeded the proliferative, migratory, and invasive abilities of lung cancer cells. Moreover, bioinformatics analysis with The Cancer Genome Atlas (TCGA) lung cancer dataset showed a negative association between ARHGAP30 expression and the Wnt signaling pathway. Enforced expression of ARHGAP30 decreased the mRNA and protein levels of ß-catenin, c-Myc, matrix metalloproteinase-2 (MMP-2) and MMP-9. Besides, the ß-catenin inhibitor XAV939 blocked the enhanced cell growth, migration, and invasion caused by ARHGAP30 knockdown. Thus, the Wnt/ß-catenin pathway mediated the functions of ARHGAP30 in lung cancer cells. CONCLUSION: ARHGAP30 acts as a tumor suppressor in lung cancer by suppressing Wnt/ß-catenin signaling.

Triptolide exhibits antitumor effects by reversing hypermethylation of WIF­1 in lung cancer cells.

Triptolide (TP) exhibits numerous biological activities, including immunosuppressive, anti­inflammatory and antitumor effects. The aim of the present study was to investigate the role of TP as a potent therapeutic drug for the treatment of lung cancer and to investigate the underlying therapeutic mechanisms. Western blot analyses and reverse transcription­quantitative polymerase chain reaction (PCR) were performed to investigate the expression of genes at transcriptional and translational levels, respectively. Methylation­specific PCR assays were conducted to investigate whether TP affects the Wnt inhibitory factor­1 (WIF­1) methylation status and subsequently affects apoptosis, migration or the invasion of lung cancer cells. The results of the present study revealed that the methylation status of WIF­1 in lung cancer cell lines A549 and H460 was significantly enhanced compared with the human normal bronchial epithelial cell line HBE, whereas treatment with TP was revealed to induce the demethylation of WIF­1. The present study aimed to investigate whether the biological activities of TP are regulated by inhibiting the Wnt signaling pathway via an increase in WIF­1 expression levels. The results of the present study revealed that Wnt signaling was suppressed in cells following treatment with TP, which was concluded by the downregulation of Axin 2 and ß­catenin expression. Further investigation demonstrated that the silencing of WIF­1 expression with small interfering RNA reversed the TP­induced upregulation of WIF­1 expression, upregulated Axin 2 and ß­catenin expression and enhanced the activation of Wnt signaling. Notably, an upregulation of cellular tumor antigen p53 expression, and downregulation of matrix metalloproteinase­9 (MMP­9) and phosphorylated­nuclear factor­κB (NF­κB) P65 (p­P65) levels was observed following TP treatment. These results suggest that the Wnt, p53 and NF­κB signaling pathways mediate the potent antitumor effects of TP. Notably, the silencing of WIF­1 did not completely recover the levels of p53, MMP­9 and p­P65 in cells treated with TP compared with the control cells, thus suggesting that TP exhibits further functions in addition to the targeting of WIF­1.

Survival analysis in Caucasian pulmonary adenocarcinoma patients based on differential targets between Caucasian and Asian population.

Ethnicity differences may contribute to the variety of overall survival in pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic driver mutations (ERSDM) profile on Caucasian survival is not well investigated. In this study, we studied epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes were selected as harboring somatic driver mutations with >10% prevalence and with different occurrence between Caucasian and Asian ethnicity. Clinical information and transcriptome sequencing of 173 Caucasian pulmonary adenocarcinoma patients with matched mutation data are retrieved from TCGA, Kaplan-Meier analyses and Cox proportional-hazards regression models are further used to analyze the effect of the ERSDM profile on overall survival. There is no significant correlation between single gene mutation and overall survival, while patients with less than two mutated genes have a better overall survival compared with those with at least two mutated genes (p = 0.034). All of these indicate that multiple mutations in the ERSDM profile may be a negative prognostic factor for overall survival in Caucasian pulmonary adenocarcinoma patients.