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To investigate the role of mitoxantrone in regulating gastric cancer cell phenotypes and the underlying mechanism. To reveal mitoxantrone-induced effects on gastric cancer cell malignancy, AGS cells were divided into different groups according to various study purposes, including negative control, 5 µmol/l mitoxantrone, 10 µmol/l mitoxantrone, 20 µmol/l mitoxantrone, anti-microRNA-negative control, anti-microRNA-211-5p, 20 µmol/l mitoxantrone+microRNA-negative control, and 20 µmol/l mitoxantrone+microRNA-211-5p groups. AGS cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide, while apoptotic rate was quantified via flow cytometry. Bcl-2 associated X-protein, activated caspase-3, phosphorylated-p65 and phosphorylated-IκBα was detected by Western blot for protein expression. Malondialdehyde was detected via colorimetry, nicotinamide adenine dinucleotide phosphate oxidase activity was detected by chemiluminescence, superoxide dismutase activity was measured via colorimetry, and microRNA-211-5p was quantified by reverse transcription-quantitative polymerase chain reaction. AGS cell proliferation, superoxide dismutase activity, as well as microRNA-211-5p expression in mitoxantrone groups (5, 10 and 20 µmol/l) were decreased compared with the negative control group, while the apoptotic rate, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were increased. Protein expression of phosphorylated-p65 and phosphorylated-IκBα (inhibitor of nuclear factor kappa B) was decreased in the 20 µmol/l mitoxantrone group. The microRNA-211-5p expression, cell proliferation, superoxide dismutase activity, and phosphorylated-p65 and phosphorylated-IκBα protein expression in anti-microRNA-211-5p group were significantly decreased in relative to anti-microRNA-negative control group, while cell apoptosis, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were increased. The microRNA-211-5p expression, cell proliferation, superoxide dismutase activity, and phosphorylated-p65 and phosphorylated-IκBα protein expression in the 20 µmol/l mitoxantrone+microRNA-211-5p group were higher than in 20 µmol/l mitoxantrone+microRNA-negative control group, while apoptotic, Bcl-2-associated X-protein and activated caspase-3 protein expression, malondialdehyde content, and nicotinamide adenine dinucleotide phosphate oxidase activity were lower than those in the 20 µmol/l mitoxantrone+microRNA-negative control group. Mitoxantrone repressed gastric cancer cell tumor property by downregulating the microRNA-211-5p/nuclear factor kappa B pathway. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is a common and harmful chronic inflammatory oral disease, characterized by the destruction of periodontal soft and hard tissues. The NLRP3 inflammasome-related pyroptosis and human periodontal ligament fibroblasts (hPDLFs) osteogenic dysfunction are involved in its pathogenesis. Studies have shown that lipoxin A4 is an endogenous anti-inflammatory mediator and BML-111 is a lipoxin A4 analog, which was found to have potent and durable anti-inflammatory effects in inflammatory diseases, but the mechanism remains unclear. The purpose of this study was to investigate whether BML-111 inhibits H2O2-induced dysfunction of hPDLFs, attenuates inflammatory responses, and identifies the underlying mechanisms. Methods: The oxidative stress model was established with H2O2, and the cell proliferation activity was measured by CCK-8. ALP staining and alizarin red staining were used to detect the osteogenic differentiation capacity of cells; flow cytometry and ELISA were used to detect cell pyroptosis; we explored the effect of BML-111 on hPDLFs under oxidative stress by analyzing the results of PCR and Western blotting. The Nrf2 inhibitor ML385 was added to further identify the target of BML-111 and clarify its mechanism. Results: BML-111 can alleviate the impaired cell proliferation viability induced by H2O2. H2O2 treatment can induce NLRP3 inflammasome-related pyroptosis, impairing the osteogenic differentiation capacity of hPDLFs. BML-111 can effectively alleviate H2O2-induced cellular dysfunction by activating the Nrf2/HO-1 signaling pathway. Conclusion: The results of this study confirmed the beneficial effects of BML-111 on H2O2-induced NLRP3 inflammasome-related pyroptosis in hPDLFs, and BML-111 could effectively attenuate the impaired osteogenic differentiation function. This beneficial effect is achieved by activating the Nrf2/HO-1 signaling pathway, therefore, our results suggest that BML-111 is a potential drug for the treatment of periodontitis. [ABSTRACT FROM AUTHOR]