Aim: To explore the mechanism by which long non-coding RNA (lncRNA) TTN-AS1 regulates osteosarcoma cell apoptosis and drug resistance via the microRNA miR-134-5p/malignant brain tumour domain containing 1 (MBTD1) axis.Results: The lncRNA TTN-AS1 was highly expressed in osteosarcoma and was associated with poor prognosis. The lncRNA TTN-AS1 promoted cell viability and inhibited apoptosis. MiR-134-5p targeted MBTD1, which was regulated by lncRNA TTN-AS1. MBTD1 was highly expressed in osteosarcoma and was associated with poor prognosis. MBTD1 promoted cell viability and inhibited apoptosis, and knockdown of MBTD1 reversed the cancer-promoting effects of lncRNA TTN-AS1. Downregulation of lncRNA TTN-AS1 reduced drug resistance.Conclusion: In osteosarcoma, lncRNA TTN-AS1 promoted the expression of MBTD1 by targeting miR-134-5p and regulated cell growth, apoptosis and drug resistance.Methods: The expression characteristics of genes in osteosarcoma patients were analysed using bioinformatics. Plasmid transfection technology was applied to silence or overexpress lncRNA TTN-AS1, miR-134-5p and MBTD1. Western blotting and quantitative polymerase chain reaction (qPCR) were used to detect protein and RNA, respectively. A cell counting kit 8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis. The effects of lncRNA TTN-AS1 and MBTD1 on osteosarcoma in vivo were studied by using a tumour burden assay.

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Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ) is a severe complication of the long-term administration of BPs. The development of BRONJ is associated with the cell death of osteoclasts, but the underlying mechanism remains unclear. In the current study, the role of Zoledronic acid (ZA), a kind of bisphosphonates, in suppressing the growth of osteoclasts was investigated and its underlying mechanism was explored. The role of ZA in regulating osteoclasts function was evaluated in the RANKL-induced cell model. Cell viability was assessed by cell counting kit-8 (CCK-8) assay and fluorescein diacetate (FDA)-staining. We confirmed that ZA treatment suppressed cell viability of osteoclasts. Furthermore, ZA treatment led to osteoclasts death by facilitating osteoclasts ferroptosis, as evidenced by increased Fe2+, ROS, and malonyldialdehyde (MDA) level, and decreased glutathione peroxidase 4 (GPX4) and glutathione (GSH) level. Next, the gene expression profiles of alendronate- and risedronate-treated osteoclasts were obtained from Gene Expression Omnibus (GEO) dataset, and 18 differentially expressed genes were identified using venn diagram analysis. Among these 18 genes, the expression of F-box protein 9 (FBXO9) was inhibited by ZA treatment. Knockdown of FBXO9 resulted in osteoclasts ferroptosis. More important, FBXO9 overexpression repressed the effect of ZA on regulating osteoclasts ferroptosis. Mechanistically, FBXO9 interacted with p53 and decreased the protein stability of p53. Collectively, our study showed that ZA induced osteoclast cells ferroptosis by triggering FBXO9-mediated p53 ubiquitination and degradation.

Designing defect‐rich MoS2/C architectures with three‐dimensional (3D) porous frame effectively improve the electrochemical performance of lithium‐ion batteries (LIBs) owing to the improved conductivity and decreased diffusion distance of Li+ ions for lithium storage. Herein, we report a reliable morphology engineering method combining with tunable defects to synthesize defect‐rich MoS2 nanosheets with a few layers entrapped carbon sheath, forming a 3D porous conductive network architecture. The defect‐rich MoS2 nanosheets with expanded interlayers can provide a shortened ion diffusion path, and realize the 3D Li+ diffusion with faster kinetics. A 3D conductive interconnected carbon network is able to improve interparticle conductivity, concurrently maintaining the structural integrity. Benefiting from these intriguing features, the as‐prepared MoS2/C architectures exhibit excellent electrochemical performance: a high reversible capacity of 1163 mAh g−1 at a current density of 0.1 A g−1 after 100 cycles and a high rate capability of 800 mAh g−1 at 5 A g−1. Defect content in MoS2/C architectures can be obtained by changing H2 concentration. Compared with the counterparts with few defects, the defect‐rich MoS2/C architectures show improved electrochemical stability with a superior cycle life, illustrating a highly reversible capacity of 751 mAh g−1 at 0.5 A g−1 after 500 cycles.

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Background: Increasing evidence indicates that andrographolide (ADG) exhibits anticancer activity against various cancer cell lines. However, its high hydrophobicity and poor bioavailability restrict its clinical application as a chemopreventative agent.Previously, we have shown that ADG-loaded solid lipid nanoparticles (SLNs) significantly enhanced the bioavailability and anti-hyperlipidemic activity of ADG. Objectives:We aimed to investigate whether ADG-SLN enhanced the bioavailability and anti-cancer efficacy of ADG in the human immortalized oral epithelial (HIOEC), precancerous leukoplakia (Leuk1), HN6, and HN30 cells that represented an in vitro model of stepwise head and neck squamous cell carcinoma development. Results:The 50% inhibitive concentration (IC50) of ADG-SLN was significantly lower than that of free ADG against HIOEC, Leuk1, and HN6 and HN30 cells. Moreover, ADG-SLN was more effective than free ADG in promoting cell cycle arrest and apoptosis. Importantly, intracellular absorption of ADG was significantly higher in HN6 cells treated with ADG-SLN compared with free ADG-treated cells.Conclusions: Our preliminary study demonstrates that ADG-SLN exhibits superior inhibitory activity against head and neck cancer and precancerous cells compared with free ADG. This effect is due to the higher efficiency of cellular uptake and intracellular absorption by ADG-SLN.

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