Flavonoids are structurally similar to steroid hormones, particularly estrogens, and therefore have been studied for their potential effects on hormone-dependent cancers. Baicalein is the primary flavonoid derived from the root of Scutellaria baicalensis Georgi. In the present study, we investigated the effects of baicalein on 17β-estradiol (E2)-induced migration, adhesion and invasion of MCF-7 and SK-BR-3 breast cancer cells. The results demonstrated that baicalein suppressed E2-stimulated wound-healing migration and cell‑Matrigel adhesion, and ameliorated E2-promoted invasion across a Matrigel-coated Transwell membrane. Furthermore, baicalein interfered with E2-induced novel G protein-coupled estrogen receptor (GPR30)-related signaling, including a decrease in tyrosine phosphorylation of epidermal growth factor receptor (EGFR) as well as phosphorylation of extracellular signal-regulated kinase (ERK) and serine/threonine kinase Akt, without affecting GPR30 expression. The results also showed that baicalein suppressed the expression of GPR30 target genes, cysteine-rich 61 (CYR61) and connective tissue growth factor (CTGF) induced by E2. Furthermore, baicalein prevented GPR30-related signaling activation and upregulation of CYR61 and CTGF mRNA levels induced by G1, a specific GPR 30 agonist. The results suggest that baicalein inhibits E2-induced migration, adhesion and invasion through interfering with GPR30 signaling pathway activation, which indicates that it may act as a therapeutic candidate for the treatment of GPR30-positive breast cancer metastasis.
Myasthenia gravis (MG) is an autoimmune disorder caused by autoantibodies directed against the postsynaptic membrane at the neuromuscular junction. Perturbation of gut microbiota is thought to contribute to the development of MG, as reflected by fecal metabolomic signatures in humans, but there have been few studies on the relationship between oral microbiota profile and MG. The current study evaluated the correlation between oral microbiota composition and diversity and anti-acetylcholinereceptor (AChR) antibody–positive MG by comparing oral microbiota communities of patients (n = 20) and healthy controls (HCs; n = 20) by 16S rRNA gene sequencing. Principal coordinate analysis and Adonis analysis revealed significant differences in oral microflora profile between the twogroups. Compared to HCs, the abundance of the phyla Firmicutes and Actinobacteria and genera Streptococcus, Rothia, and Lachnoanerobaculum was significantly increased whereas that of phyla Proteobacteria and Spirochaetotaand genera Neisseria, Haemophilus, and Treponema was significantly decreased in MG patients. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the biosynthesis of ansamycins and amino acid metabolism pathways were altered in MG. These results indicate that oral microbiota composition is perturbed in patients with anti-AChR antibody–positive MG, providing new potential avenues for targeted therapeutic interventions.
The safety and toxicity of CeO2 nanoparticles (nanoceria) are of growing concern due to their potential applications in biological and medical fields based on the radical scavenging and UV-filtering properties. In this paper, the ultrafine monodisperse (2-5 nm) water-insoluble (CeO2-P) and water-soluble nanoceria modified with various functional groups of dextran (CeO2-dextran), polyacrylic acid (CeO2-PAA) and ethylenediamine (CeO2-EDA) on surface were synthesized via alkaline-based precipitation and inverse microemulsion methods. The cell uptaking, oxidative stress and cytotoxicity of these nanoceria on human gastric cancer cell line (BGC-803) were systematically investigated. It is found that the cell uptaking of nanoceria is largely relied on the function groups on its surfaces and followed the order: CeO2-P > CeO2-EDA > CeO2-dextran > CeO2-PAA. Moreover, the oxidative stress of BGC-803 cells is obviously affected by the antioxidant capacity of nanoceria determined by Ce3+/Ce4+ ratio, which eventually causes the cell viability variable once the nanoceria entered into BGC-803 cells. In addition, the cell viability is also closely correlated with the concentration and surface characteristics of nanoceria. The cytotoxicity of nanoceria on BGC-803 cells is largely dependent on its surface functional groups. Our work may provide guidance on the cytotoxicity of ultrafine monodisperse nanoceria for their uses in biological and medical fields.
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