OBJECTIVE: It is of great interest to identify the oxidation products of sesamol that may be beneficial to humans. This study was undertaken to identify the oxidation products of sesamol and investigate their antioxidant and cytotoxic activities.

MATERIALS AND METHODS: Using the ferricyanide oxidation approach, four oxidation products of sesamol (2, 3, 20 & 21) have been identified. Structural elucidation of these compounds was established on the basis of their detailed NMR spectroscopic analysis, mass spectrometry and x-ray crystallography. Additionally, a formation mechanism of compound 20 was proposed based on high-resolution mass spectrometry-fragmentation method. The antioxidant activities of these compounds were determined by the DPPH, FRAP, and ABTS assays. The in vitro antiproliferative activity of these compounds was evaluated against a panel of human cancer cell lines as well as non-cancerous cells.

RESULTS: Two oxidation products of sesamol were found to contain an unusual methylenedioxy ring-opening skeleton, as evidenced by spectroscopic and x-ray crystallographic data. Among all compounds, 20 displayed impressive antiproliferative activities against a panel of human cancer cell lines yet remained non-toxic to noncancerous cells. The antioxidant activities of compound 20 are significantly weaker than sesamol as determined by the DPPH, FRAP, and ABTS assays.

METHODS: We performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330.

RESULTS: We replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis.

METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays.

RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential.