Current Pharmaceutical Biotechnology - Online First

This study aimed to investigate the effect of dihydroartemisinin (DHA) on DU145 cells and the role of NR2F2 (COUP-TFII) and its potential target genes in this process.

GSE122625 was used to identify differentially expressed genes (DEGs) between the DHA-treated and control groups. Protein-protein interaction (PPI) network analysis was performed to identify hub genes, and the ChEA3 database was used to identify potential transcription factors. qRT-PCR and Western blot were used to validate the expression of genes of interest and functional assays were performed to evaluate the effect of DHA on DU145 and PC-3 cells. To solidify the regulatory relationship of NR2F2 with EFNB2, EBF1, ETS1, and VEGFA, a Chromatin Immunoprecipitation (ChIP) experiment was performed.

We identified 85 DEGs in DU145 cells treated with DHA, and PPI network analysis identified NR2F2 as a hub gene and potential transcription factor. The regulatory network of NR2F2 and its potential target genes (EFNB2, EBF1, ETS1, and VEGFA) was constructed, and the expression of these genes was upregulated in DHA-treated cells compared to control cells. Functional assays showed that DHA treatment inhibited epithelial-mesenchymal transition, reduced inflammation, and promoted apoptosis in DU145 and PC-3 cells. Furthermore, NR2F2 knockdown receded the DHA-induced upregulation of target genes and functional changes of DU145 and PC-3 cells. The outcomes of ChIP unequivocally pointed to a positive regulatory role of NR2F2 in these gene expressions.

Our study suggests that DHA treatment affects the functions of DU145 and PC-3 cells by regulating the expression of NR2F2 and its potential target genes, and NR2F2 may serve as a potential therapeutic target for prostate cancer.

Atherosclerosis (AS) is an inflammatory disease of arterial intima driven by lipids. Liver X receptor alpha (LXRα) and peroxisome proliferator-activated receptor alpha (PPARα) agonists are limited in the treatment of AS due to their off-target effects and serious side effects. Therefore, this study was designed to construct a novel nanoparticle (NP) and evaluate its mechanism of action on inflammation inhibition and lipid reduction in AS.

We synthesized cRGD-platelet@MnO/MSN@PPARα/LXRα NPs (cRGD-platelet-NPs) and confirmed their size, safety, and targeting ability through various tests, including dynamic light scattering and immunofluorescence. In vivo and in vitro experiments assessed cell proliferation, apoptosis, inflammation, and plaque formation. Finally, the NF-κB signaling pathway expression in rat aorta was determined using a western blot.

The synthesis of cRGD-platelet-NPs was successful; the particle size was approximately 150 nm, and the PDI was below 0.3. They could be successfully absorbed by cells, exhibiting high safety in vivo and in vitro. The cRGD-platelet-NPs successfully reduced plaque formation, improved lipid profiles by lowering LDL-cholesterol, total cholesterol, and triglycerides, and raised HDL-cholesterol levels. Additionally, they decreased inflammatory markers in the serum and aortic tissue, suggesting reduced inflammation. Immunohistochemistry and western blot analyses indicated that these NPs could not only promote M2 macrophage polarization but also suppress the NF-κB signaling pathway.

The newly developed cRGD-platelet-NPs with high safety are a promising approach to AS treatment, which can regulate ABCA1, reduce the formation of AS plaques, and enhance cholesterol efflux. The mechanism may involve the suppression of the NF-κB signaling pathway.