FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.

Tumor metastasis is the major cause of breast cancer morbidity and mortality. It has been reported that the F-box protein FBXO3 functions as an E3 ubiquitin ligase in regulating various biological processes, including host autoimmune, antiviral innate immunity, and inflammatory response. However, the role of FBXO3 in tumor metastasis remains elusive. We have previously shown that ΔNp63α is a common inhibitory target in oncogene-induced cell motility and tumor metastasis. In this study, we show that FBXO3 plays a vital role in PI3K-mediated breast cancer metastasis independent of its E3 ligase activity and ΔNp63α in breast cancer cells and in mouse. FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis. Mechanistically, FBXO3 disrupts the interaction between USP4 and aspartyl aminopeptidase (DNPEP), thereby protecting USP4 from DNPEP-mediated degradation. Furthermore, p110αH1047R facilitates the phosphorylation and stabilization of FBXO3 in an ERK1-dependent manner. Knockdown of either FBXO3 or USP4 leads to significant inhibition of PI3K-induced breast cancer metastasis. Clinically, elevated expression of p110α/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.

Urolithin B alleviates Helicobacter pylori-induced inflammation and oxidative stress in mice.

BACKGROUND: Helicobacter pylori is one of the most common chronic bacterial infections. Active eradication of H. pylori infection is rare due to the fact that most infected patients are asymptomatic and the use of large amounts of antibiotics in eradication therapy leads to severe side effects. Urolithin B (UB) is an additional major intestinal metabolite of ellagic acid (EA), which has been shown to possess anti-inflammatory, antioxidant, and antiapoptotic biological activities. Preventing the incidence of H. pylori-related gastric disease and reducing the damage to the host by H. pylori is a current approach to control H. pylori infection. In this study, we explored the effect of UB on H. pylori infection. MATERIALS AND METHODS: The effects of UB on inflammation and oxidative stress induced by H. pylori in vivo and in vitro were investigated by qPCR, ELISA, HE staining, IHC staining, etc. RESULTS: UB reduced the adhesion and colonization of H. pylori and improved H. pylori-induced inflammation and oxidative stress in vivo and in vitro. Moreover, UB had better anti-inflammatory and antioxidant effects than clarithromycin (CLR) and metronidazole (MET). In addition to inhibiting the secretion of CagA, UB reduced tissue damage by H. pylori infection. CONCLUSIONS: UB was effective in improving damage caused by H. pylori.

Anti-Helicobacter pylori activity of Fagopyrum Tataricum (L.) Gaertn. Bran flavonoids extract and its effect on Helicobacter pylori-induced inflammatory response.

Tartary buckwheat flavonoids have a variety of effects on anti-inflammatory, anti-oxidation, as well as anti-tumor and are valuable for academic research and industrial application. Helicobacter pylori (H. pylori) infection is associated with various gastrointestinal diseases in humans, and an increase in its resistance has led to the failure of many drugs. In this study, we quantified the main monomers of tartary buckwheat (Fagopyrum Tataricum (L.) Gaertn.) bran flavonoids extract through HPLC analysis. Then, we investigated the anti-H. pylori activity and the effect on cell inflammation of tartary buckwheat flavonoids extract and its four main flavonoid monomers (rutin, quercetin, kaempferol, and nicotiflorin). The results showed that tartary buckwheat flavonoids extract and its four flavonoid monomers could inhibit the growth of H. pylori and down-regulate the expression of proinflammatory factors IL-6, IL-8, and CXCL-1 in H. pylori-induced GES-1 cells. Moreover, we also confirmed that tartary buckwheat flavonoids extract could reduce the expression of virulence factor gene of H. pylori. In summary, tartary buckwheat can alleviate the cell inflammation induced by H. pylori, which provides a theoretical basis for the development of tartary buckwheat healthcare products.