Cnidium lactone is effective in the maintenance of bone mass in various osteoporosis models; however, the precise molecular mechanisms are not understood. In this study, we investigated the effects and underlying mechanisms of action of cnidium lactone on receptor activator of NF-jB ligand (RANKL)induced osteoclastogenesis. Cnidium lactone dose-dependently inhibited osteoclast differentiation and formation, decreased the bone-resorbing activity of osteoclasts, and downregulated the expression of osteoclast differentiation marker genes. Cnidium lactone treatment considerably reduced RANKLinduced p38 MAPK and PI3K-Akt signal activity in RAW264.7 cells. The cnidium lactone-induced osteoclastogenesis was significantly attenuated by inhibition of p38 and PI3K through pretreatment with SB203580 and LY294002, respectively. Furthermore, cnidium lactone inhibited the expression of c-Fos and NFATc-1 with dose-dependently and enhanced by SB203580 and LY294002. In conclusion, cnidium lactone inhibits osteoclast differentiation through p38 MAPK and PI3K-Akt signalling pathway/c-Fos/ NFATc1 signalling pathway.

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Background: The Italian Spine Youth Quality of Life (ISYQOL) questionnaire is a tool used to evaluate health-related quality of life in adolescents with Idiopathic Scoliosis. The study aimed to undertake the process of cultural adaptation of the ISYQOL questionnaire into Simplified Chinese. Methods: The translation from Italian into Simplified Chinese was performed. It involved 138 adolescents whose Cobb angle ranged between 20-40 degrees, 50 wearing the brace and 88 not wearing the brace. Statistical analysis calculated the reliability, floor and ceiling effects of the ISYQOL. After that, construct validity was measured by analyzing the ISYQOL relationship Scoliosis Research Society-22 patient Questionnaire (SRS-22). Results: There were no floor or ceiling effects in ISYQOL questionnaire. Cronbach’s alpha coefficient evaluated for Internal consistency was 0.75 without the brace and 0.88 with the brace. Intraclass correlation coefficients assessed with the use of the test-retest method was 0.72 without the brace and 0.80 with the brace. A strong relationship exists between the ISYQOL measure and SRS-22 scores (rho=0.63; p< 0.01), reflecting the high validity of the questionnaires. Both ISYQOL and SRS-22 scores showed no statistical difference between groups with and without the brace (p>0.05). Conclusions: Trans-cultural validation in Chinses language showed the reliability and validity of the ISYQOL

Osteosarcoma (OS) is one of the most prevalent malignancies with a bad prognosis. Oxidative stress is closely associated with various type of cancer. The present study aimed to establish an oxidative stress-related gene prognostic signature. Supported by The Cancer Genome Atlas and Gene Expression Omnibus, the least absolute shrinkage and selection operator regression, Cox regression, receiver operating characteristic curves and Kaplan-Meier survival analysis were used to construct and validate a prognostic signature and the derived risk score. Tumor microenvironment scores and immune infiltration levels in OS were calculated. Correlation between these parameters and risk score was analyzed. In addition, single analysis of each hub gene was performed. Finally, a series of molecular experiments was used to detect the role of MAP3K5 (one of the hub genes) in OS. A total of five genes most associated with OS prognosis were identified as independent predictors, namely catalase (CAT), mitogen-activated protein kinase 1 (MAPK1), glucose-6-phosphate dehydrogenase (G6PD), mitogen-activated protein kinase kinase kinase 5 (MAP3K5) and C-C motif chemokine ligand 2 (CCL2). Based on the signature, higher risk score indicated poorer prognosis. Nomogram performed well and reliably predicted 3-and 5-year survival rate in OS. Patients with increasing risk scores had higher tumor purity and lower immune infiltration levels. Compared with an osteoblast cell line, the expression of CAT, CCL2, MAPK1 and G6PD was upregulated and MAP3K5 was downregulated. MAP3K5 inhibited cellular proliferation and motility, promoted cellular apoptosis and induced reactive oxygen species generation. Overall, the signature could effectively predict the prognosis of patients with OS and were expected to be potential biomarkers. And it provided new ideas for understanding the interactions between oxidative stress and OS.

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