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Small Heterodimer Partner (SHP; NR0B2) is an orphan receptor that acts as a transcriptional regulator, controlling various metabolic processes, and is a potential therapeutic target for cancer. Examining the correlation between the expression of NR0B2 and the risk of gastric diseases could open a new path for treatment and drug development. The Gene Expression Omnibus (GEO) database was utilized to explore NR0B2 gene expression profiles in gastric diseases. Co-expressed genes were identified through Weighted Correlation Network Analysis (WGCNA), and GO enrichment was performed to identify potential pathways. The Xcell method was employed to analyze immune infiltration relationships. To determine the potential causal relationship between NR0B2 expression and gastric diseases, we identified six single-nucleotide polymorphisms (SNPs) as a proxy for NR0B2 expression located within 100 kilobases of NR0B2 and which are associated with triglyceride homeostasis and performed drug-target Mendelian randomization (MR). Bioinformatics analysis revealed that NR0B2 expression levels were reduced in gastric cancer and increased in gastritis. GO analysis and Gene Set Enrichment Analysis (GSEA) showed that NR0B2 is widely involved in oxidation-related processes. Immune infiltration analyses found that NR0B2 was associated with Treg. Prognostic analyses showed that a low expression of NR0B2 is a risk factor for the poor prognoses of gastric cancer. MR analyses revealed that NR0B2 expression is associated with a risk of gastric diseases (NR0B2 vs. gastric cancer, p = 0.006, OR: 0.073, 95%CI: 0.011–0.478; NR0B2 vs. gastric ulcer, p = 0.03, OR: 0.991, 95%CI: 0.984–0.999; NR0B2 vs. other gastritis, p = 0.006, OR:3.82, 95%CI: 1.468–9.942). Our study confirms the causal relationship between the expression of NR0B2 and the risk of gastric diseases, and highlights its role in the progression of gastric cancer. The present study opens new avenues for exploring the potential of drugs that either activate or inhibit the NR0B2 receptor in the treatment of gastric diseases. [ABSTRACT FROM AUTHOR]

Despite several decades of research, the beneficial effect of flavonoids on health is still enigmatic. Here, we focus on the antioxidant effect of flavonoids, which is elementary to their biological activity. A relatively new strategy for obtaining a more accurate understanding of this effect is to leverage computational chemistry. This review systematically presents various computational chemistry indicators employed over the past five years to investigate the antioxidant activity of flavonoids. We categorize these strategies into five aspects: electronic structure analysis, thermodynamic analysis, kinetic analysis, interaction analysis, and bioavailability analysis. The principles, characteristics, and limitations of these methods are discussed, along with current trends. [ABSTRACT FROM AUTHOR]

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in 'biotargeting' quercetin. [ABSTRACT FROM AUTHOR]