Demethylzeylasteral is one of the extracts of Tripterygium wilfordii Hook F, which plays important roles in multiple biological processes such as inflammation inhibition, as well as immunosuppression. However, anti-cancer function and the underlying mechanisms of demethylzeylasteral in melanoma cells remain unclear. In this study, we demonstrate that demethylzeylasteral has an anti-tumor property in melanoma cells. Demethylzeylasteral not only inhibits cell proliferation through cell cycle arrest at S phase, but also induces cell apoptosis in melanoma cells. MCL1 is an anti-apoptotic protein in BCL2 family, and amplifies frequently in multiple human cancers. MCL1 is also known as a potential contributor for the resistance of BCL2 inhibitors, as well as various chemotherapeutic drugs. MCL1 is, therefore, regarded as a potential target for cancer therapy. Here, for the first time, we unveil that demethylzeylasteral suppresses the expression of MCL1. Interestingly, MCL1 interacts with S phase-related protein CDK2, and thereby inhibits it’s ubiquitin-dependent degradation. Together, demethylzeylasteral is a promising anti-tumor compound in melanoma cells. Demethylzeylasteral is also a potential inhibitor of MCL1.

BackgroundThe purpose of the present study was to examine the expression levels of microRNA-9 (miR-9) in osteosarcoma tissues and normal bone tissues, and investigate the relationships between miR-9 expression, clinicopathological features and the prognosis of patients with osteosarcoma.MethodsThe expression levels of miR-9 in osteosarcoma tissues and corresponding non-cancerous tissues were detected using a real-time quantitative assay. Differences in patient survival were determined using the Kaplan–Meier method and a log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values.ResultsCompared to non-cancerous bone tissues, the expression levels of miR-9 in osteosarcoma tissues were significantly elevated (P < 0.001). We found that the expression level of miR-9 was significantly associated with tumor size (P = 0.011), clinical stage (P = 0.009) and distant metastasis (P < 0.001). The Kaplan–Meier curve showed that patients with low miR-9 expression survived significantly longer than patients with high miR-9 expression (P = 0.0017). Multivariate analysis suggested that miR-9 expression level (P = 0.002) is an independent prognostic factors for overall survival.ConclusionsThe findings of our study suggest that increased miR-9 expression has a strong correlation with the aggressive progression of osteosarcoma and its overexpression is a statistically significant risk factor affecting overall survival, suggesting that increased miR-9 expression could be a valuable marker of tumor progression and for prognosis of osteosarcoma.

Melanoma, the most aggressive human skin tumor, has a very short survival time, and there are currently no effective treatments. Alterations in cell metabolism, such as enhanced aerobic glycolysis, have been identified as hallmarks of cancer cells. In the present study, bioinformatics studies using online databases revealed that FOXO3a expression was lower in melanoma tissues compared with normal tissues and nevus. Additionally, Kaplan-Meier analysis showed that high expression of FOXO3a predicted an improved prognosis for patients with melanoma. Furthermore, Pearson correlation analysis indicated that the expression of FOXO3a was positively correlated with SIRT6 expression and negatively correlated with the expression levels of a number of glycolysis-associated genes. Chromatin immunoprecipitation and luciferase assays showed that FOXO3a was enriched in the SIRT6 promoter region and promoted its transcription. Then, SIRT6 was overexpressed in FOXO3a-knockdown MV3 cells and downregulated in FOXO3a-overexpressing MV3 cells by using lentivirus-mediated stable infection. The results showed that SIRT6 knockdown or overexpression rescued the effects of FOXO3a overexpression or knockdown, respectively, on glycolysis, as determined by glucose uptake, glucose consumption and lactate production assays, the expression of glycolytic genes and glucose stress flux tests. SIRT6 overexpression also suppressed FOXO3a knockdown-induced tumor growth in a mouse model. The present findings indicated that the FOXO3a-SIRT6 regulatory axis inhibited glucose metabolism and tumor cell proliferation in melanoma, and provided novel insight into potential therapeutic strategies to treat this disease.

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Purpose: Temporomandibular disorder (TMD) causes masticatory muscle pain and mouth opening limitations and affects patients’ ability to eat, practice oral health and perform other activities of daily living. Although the benefits of low-energy lasers in treating TMD have been reported, the results vary greatly depending on the equipment used and the energy output. This study systematically evaluated the efficacy of a low-level gallium aluminium arsenide (GaAlAs) laser treatment for TMD with myofascial pain and maxillary pain. Methods: We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases for randomized controlled trials (RCTs) published since database inception to April 5, 2020, that compared low-level laser treatment to sham/placebo treatment or no intervention in patients suffering from TMD with myofascial pain. Three reviewers independently screened the literature, extracted data, and assessed the quality of the included studies according to the risk-of-bias tool recommended by the Cochrane Handbook V.5.1.0 (Cochrane Collaboration, London, UK). Then, a meta-analysis was performed using RevMan 5.3 and Stata 15.1 software. Results: The data from 8 randomized controlled trials including 181 patients were analyzed. The severity of myofascial TMD pain (measured on a visual analogue scale, VAS) at the end of treatment was significantly different between the control laser therapy and the low-level GaAlAs laser therapy (weighted mean difference [WMD] = −0.76, 95% confidence interval [CI] −1.51 to 0.01, P = .046); at 3 to 4 weeks after treatment, there was no significant difference (WMD = 1.24, 95% CI −0.04 to 2.51, P = .057). In addition, there was no significant improvement in maximum mouth opening (MMO) at the end of treatment (WMD = −0.03, 95% CI −4.13 to 4.06, P = .987) or at 3 to 4 weeks after treatment (WMD = 1.22, 95% CI −2.94 to 5.39, P = .565). Conclusions: The results of this study suggest that there is insufficient evidence to indicate an efficacy of low-level GaAlAs laser therapy in improving TMD pain and maximal oral opening. These results suggest that clinicians should make appropriate recommendations to inform patient decision-making.