Spinal cord injury (SCI) is a central nervous system (CNS) trauma involving inflammation and oxidative stress, which play important roles in this trauma’s pathogenesis. Therefore, controlling inflammation is an effective strategy for SCI treatment. As a hormone, melatonin is capable of producing antioxidation and anti-inflammation effects. In the meantime, it also causes a neuroprotective effect in various neurological diseases. Nrf2/ARE/NLRP3 is a well-known pathway in anti-inflammation and antioxidation, and Nrf2 can be positively regulated by melatonin. However, how melatonin regulates inflammation during SCI is poorly explored. Therefore, it was investigated in this study whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model. Methods: A model of SCI was established in C57BL/6 mice and PC12 cells. The motor function of mice was detected by performing an open field test, and Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling were carried out to evaluate the survival of neurons. Mitochondrial dysfunction was detected by transmission electron microscopy (TEM) and by assessing the mitochondrial membrane potential. In addition, the expression of NLRP3 inflammasome and oxidative-stress-related proteins were detected through Western blot and immunofluorescence double staining. Results: By inhibiting neuroinflammation and reducing neuronal death, melatonin promotes the recovery of neuromotor function. Besides this, melatonin is able to reduce the damage that causes neuronal mitochondrial dysfunction, reduce the level of reactive oxygen species (ROS) and malondialdehyde, and enhance the activity of superoxide dismutase and the production of glutathione peroxidase. Mechanically, melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling. Conclusions: In conclusion, melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, reducing mitochondrial dysfunction, and improving the recovery of nerve function after SCI.

In this study, the purpose is to examine the impact of nano-hydroxyapatite (Nano-HAP) on human osteosarcoma cell (U2OS) growth and apoptosis (cell death). For reaching this goal an apoptosis kit was employed to determine the influence of Nano-HAP on apoptosis in human osteosarcoma cells U2OS, which were treated with different doses of Nano-HAP; FDA staining was used to elucidate the effect of Nano-HAP on cell adhesion. U2OS adhesion was not affected by Nano-HAP at different concentrations, however the production of U2OS was dramatically reduced. U2OS osteosarcoma cell growth was considerably inhibited at the doses of 50 g/ml and 800 g/ml, respectively. In conclusion, osteosarcoma cell growth and apoptosis are greatly inhibited by nano-HAP, although there is no clear linear link between nanoparticle concentration and the impact.

Background： Proteasome inhibition represents a promising strategy for cancer therapy. Bortezomib, primarily targeting the chymotrypsin-like activity of PSMB5, has been proven effective in several tumors. However, variable sensitivity exits in response to bortezomib, which may be partially due to differences in the expression of proteasome subunits. Methods and Results: In this study, we investigated whether miR-383 affects the proteasome subunits expression in osteosarcoma (OS) cells, and if so, whether OS cells display differential sensitivity to bortezomib concerning miR-383 expression. We detected a decreased miR-383 expression in OS cells and tissues. Then we found a negative correlation between bortezomib cytotoxicity and proteasome 20S core particle subunit β5 (PSMB5) expression level. Intriguingly, we found that PSMB5 is a target of miR-383. Higher expression of miR-383 led to decreased PSMB5 expression and exhibited greater sensitivity to bortezomib in OS cells. Conclusions: In summary, our results represent the first comprehensive analysis of the role of miR-383 in OS. The results suggest that miR-383 may enhance the anticancer effect of bortezomib through PSMB5 repression, providing a novel therapeutic strategy in OS and a new pathway for proteasome regulation.