Atherosclerosis is a chronic inflammation condition resulting from the interaction between lipoproteins, monocyte-derived macrophages, T lymphocytes, and other cellular elements in the arterial wall. Macrophage-derived foam cells play a key role in both early and advanced stage of atherosclerosis. Previous studies have shown that berberine could inhibit foam cell formation and prevent experimental atherosclerosis. However, its underlying molecular mechanisms have not been fully clarified. In this study, we explored the cholesterol-lowering effects of berberine in macrophage-derived foam cells and investigated its possible mechanisms in prevention and treatment of atherosclerosis. Here, we demonstrated that berberine could inhibit atherosclerosis in apolipoprotein E-deficient mice and induce cholesterol reduction as well as decrease the content of macrophages. Berberine can regulate oxLDL uptake and cholesterol efflux, thus suppresses foam cell formation. Mechanisms study showed that berberine can suppress scavenger receptor expression via inhibiting the activity of AP-1 and upregulate ATP-binding cassette transporter via activating Nrf2/HO-1 signaling in human macrophage. In summary, berberine significantly inhibits atherosclerotic disease development by regulating lipid homeostasis and suppressing macrophage foam cell formation.

Accumulating evidence indicates that the dysregulation of circular RNAs (circRNAs) contributes to tumor progression; however, the regulatory functions of circRNAs in renal cell carcinoma (RCC) remain largely unknown. In this study, the function and underlying mechanism of circAMOTL1L in RCC progression were explored. qRT-PCR showed the downregulation of circAMOTL1L in RCC tissues and cell lines. The decrease in circAMOTL1L expression correlated with the tumor stage, metastasis, and poor prognosis in patients with RCC. Functional experiments revealed that circAMOTL1L inhibited cell proliferation and increased apoptosis in RCC cells. Subcutaneous implantation with circAMOTL1L-overexpressing cells in nude mice decreased the growth ability of the xenograft tumors. Mechanistically, circAMOTL1L served as a sponge for miR-92a-2-5p in upregulating KLLN (killin, p53-regulated DNA replication inhibitor) expression validated by bioinformatics analysis, oligo pull-down, and luciferase assays. Further, reinforcing the circAMOTL1L–miR-92a-2-5p–KLLN axis greatly reduced the growth of RCC in vivo. Conclusively, our findings demonstrate that circAMOTL1L has an antioncogenic role in RCC growth by modulating the miR-92a-2-5p–KLLN pathway. Thus, targeting the novel circAMOTL1L–miR-92a-2-5p–KLLN regulatory axis might provide a therapeutic strategy for RCC.

Apigenin (AP) is a plant flavonoid with potential biomedical applications. To enhance the anti-tumour effect, AP was deuterated via hydrogen–deuterium exchange under hydrothermal conditions. The anti-tumor effects of deuterated AP (D-AP) were then tested on HCT116 cells and on a murine model of turpentine-induced inflammation. Cell cycle progression and cell proliferation were measured by flow cytometry, and in vivo immuno-inflammation was evaluated by quantitating glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography. According to the mass spectral results, the efficiency of AP deuteration was 62.96%. For both the two groups of AP and D-AP at 24 h and 48 h, there were an obvious increase on perception of G2 phage. Apigenin showed the ability of blocking in G2 phage to inhibit cellular proliferation. Additionally, D-AP induced early apoptosis in more cells than did AP (12.1% vs. 10.4%). Moreover, D-AP induced a more severe process of anti-inflammation during the early period, resulting in a more effective anti-inflammatory response. Therefore, given the innate ability of D-AP to block cell proliferation and induce early apoptosis, we conclude that deuteration enhances the systemic anti-cancer effect of this flavonoid.