Background/Aim: Sorafenib has been reported to show anti-osteosarcoma (anti-OS) efficacy by inhibiting metastasis; however, a phase II trial suggested that further combination with other agents could be necessary to achieve permanent remission. Herein, we aimed to identify whether amentoflavone, an abundant natural bioflavonoid found in many medicinal plants, can improve the treatment efficacy of sorafenib in OS. Materials and Methods: Cell viability, metastasis, apoptosis, and nuclear translocation of NF-ĸB after amentoflavone combined with sorafenib were assayed by MTT, transwell migration/invasion, western blotting, flow cytometry, and immunofluorescence staining, respectively. Results: The sorafenib-induced cytotoxicity and apoptosis of U-2 OS was enhanced by combining treatment with QNZ (NF-ĸB inhibitor) or amentoflavone. NF-ĸB nuclear translocation, NF-ĸB phosphorylation, and metastasis capacity of U-2 OS cells were inhibited by amentoflavone combined with sorafenib. Conclusion: Amentoflavone may sensitize OS to sorafenib treatment by inducing intrinsic and extrinsic apoptosis and inhibiting ERK/NF-ĸB signaling transduction.
In the title compound, C20H16N4O, the non-H atoms of the benzotriazole ring system and those of the methylphenol group are essentially coplanar, with an r.m.s. deviation of 0.004 (2) Å. The mean plane of these atoms forms a dihedral angle of 60.9 (2)° with the phenyl ring. There is an intramolecular O—H⋯N hydrogen bond between the phenol and benzotriazole groups.
Background
Previous studies have reported that vitamin D supplement could improve fracture healing, but evidence regarding the role of vitamin D supplements in spinal fusion was limited. Thus, this study aimed to evaluate the effectiveness of oral vitamin D supplements on fusion outcomes in patients undergoing lumbar spinal fusion.
Methods
This randomized, double-blind, parallel-designed, active-control trial included the patients who planned for elective lumbar spinal fusion. Eligible patients were randomly assigned to receive either daily vitamin D3 (cholecalciferol) 800 IU and daily calcium citrate 600 mg (experimental group) or only daily calcium citrate 600 mg (control group). All supplements were given from postoperative day 1 and lasted for 3 months. Primary outcome was postoperative 1-year fusion rate, and secondary outcomes included time to fusion, Oswestry Disability Index (ODI), and visual analogue scale (VAS) for pain.
Results
Among the included 34 patients (21 in the experimental group and 13 in the control group), baseline 25-hydroxyvitamin D (25[OHVitD) level was 26.7 (10.4) ng/ml. Preoperative prevalence of vitamin D deficiency and insufficiency were 23.5% and 47.1%, respectively. Postoperative 1-year fusion rate was not significantly different between the two groups (95.2% vs. 84.6%, P = 0.544). The experimental group had significantly shorter time to fusion (Kaplan–Meier estimated: 169 days vs. 185 days [interquartile range: 88–182 days vs. 176–324 days], log-rank test: P = 0.028), lower postoperative 6-month ODI (P < 0.001), and lower postoperative 6-month VAS (P < 0.001) than the control group. Time to fusion was significantly and negatively correlated with preoperative, postoperative 3-month, and 6-month 25(OH)VitD levels (all P < 0.01).
Conclusion
The patient with vitamin D supplements had shorter time to fusion, better spinal function and less pain after elective spinal fusion. Further research is warranted to identify the patients who can benefit the most from vitamin D supplements and the appropriate dose of vitamin D supplements.
Trial registration
ClinicalTrials.gov, NCT05023122. Registered 20 August 2021. Retrospectively registered, http://clinicaltrials.gov/ct2/show/NCT03793530.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.