Curcumol, a polyphenol compound derived from the rhizome of Curcuma, has been established as an antitumor compound against multiple types of cancer, including gastric (GC), lung, liver and breast cancer. However, the molecular mechanisms undelying its anticancer activity in GC are still unclear. In this study, the antitumor efficacy of curcumol was ascertained in human gastric adenocarcinoma MGC-803 cells. An MTT assay was used to assess the viability of the MGC-803 cells treated by curcumol. The results of the Annexin V/propidium iodide (PI) staining followed by fluorescence activated cell sorting (FACS) analysis demonstrated that the cell cycle was arrested in the G2/M phase by curcumol. Annexin V-FITC/PI double staining followed by FACS analysis revealed that curcumol induced apoptosis of MGC-803 cells. FACS analysis after the cells were loaded with a DFCH-DA probe revealed that the level of reactive oxygen species (ROS) increased after the cells were treated with curcumol. In adittion, FACS analysis after the cells were loaded with JC-1 revealed that the level of mitochondrial membrane potential (MMP) decreased after the cells were treated with curcumol. Furthermore, the downregulation of isocitrate dehydrogenase 1 (IDH1) was observed in the MGC-803 cells after being treated with curcumol as determined by western blotting and RT-qPCR. In conclusion, we elucidated the antitumor effect of curcumol on MGC-803 cells and the involved mechanisms related to the induction of apoptosis, the increase of ROS, the decrease of MMP and the downregulation of IDH1.

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3D poly(glycerol-sebacate)/poly(L-lactic-acid) (PGS/PLLA) scaffolds, produced by thermally induced phase separation (TIPS) method were treated with oxygen plasma in order to reduce the hydrophobicity of the PGS/PLLA membranes. After the oxygen plasma treatment, the pore size of scaffolds became uniform as well as an increasing in the roughness of the surface. No influence on chemical characteristics such as composition and bond types of PLLA was detected after the treatment. However, the change in the ratio of the scaffold elements before and after the oxygen plasma treatment was detected. Oxygen plasma treatment reduced the average of water contact angle of the TIPS film from 103.7± 10.1 to 64.7± 12.6 at the maximum exposure time (970 s) and power (100 W). The results showed that the goat temporomandibular joint (TMJ) cells attached well to the surface of the oxygen plasma modified scaffold. Furthermore, this modification significantly enhanced cell viability, increased cell proliferation and expression of related genes (Collagen type I mRNA and Collagen type II mRNA). The results demonstrated that it is a promising modification method to promote applications of PGS/PLLA based scaffolds to the regeneration of TMJ discs.

I. Background: The roles of antioxidants on the energy metabolism of disc cells are not clear. In this study, we clarified the roles of antioxidant N-acetylcysteine (NAC) on the energy metabolism of goat temporomandibular joint (TMJ) disc cells exposed to hypoxia. II. Methods and Results: The Isolated and cultured goat TMJ disc cells were divided into control, NAC group, cobalt chloride (CoCl2) group, and CoCl2 with NAC group, exposed to 21% O2 and 2% O2. The glucose consumption, lactate content, intracellular ATP, ROS, HIF-1α, GLUT1, LDHA, PKM2 and PGK1 expressions were detected respectively. Under the hypoxia model, NAC inhibited the mRNA expression of HIF-1α, GLUT1, LDHA, PKM2, and PGK1. And it significantly decreased the lactate content in the culture supernatant and the intracellular ROS. However, NAC increased glucose consumption and simultaneously promoted the production of ATP in goat TMJ disc cells under hypoxia. We speculated that NAC would transfer energy metabolism toward oxidative phosphorylation under hypoxia. And NAC would become a potential therapeutic target for TMJ disc engineering and disease study. III. Conclusions: The antioxidant NAC promoted the proliferation of hypoxia-inducible goat TMJ disc cells, and the CoCl2 group (21% O2) was promoted effectively (P < 0.05). NAC promoted glucose consumption in culture supernatants under hypoxia and significantly reduced lactate production (P < 0.01). NAC effectively eliminated intracellular ROS expression in hypoxia-inducible cells (P < 0.001) and promoted intracellular ATP production (P < 0.05). However, NAC inhibited the relative mRNA level of HIF-1α, GLUT1, LDHA, PKM2, and PGK1 (P < 0.05).

Temporomandibular joint (TMJ) disc degeneration is a common disease characterized by a decrease in metabolic function. The present study aimed to investigate the pathogenesis of TMJ disc degeneration by analyzing the effects of oxygen and glucose concentrations on metabolism in a simulated TMJ disc cell growth environment. Cell samples were divided into 10 groups and cultured in different nutritional environments, including 21 and 2% O 2 partial pressures and various glucose concentrations (0, 0.5, 3, 5.5 and 22.5 mmol/l). Cell proliferation, extracellular matrix content, mitochondrial function, and cell metabolism were subsequently analyzed. The results demonstrated that hypoxia and a low glucose concentration inhibited cell growth, and low glucose concentration inhibited extracellular matrix synthesis and adenosine 5'-monophosphate-activated protein kinase expression. Hypoxic conditions also induced a compensatory increase in the number of mitochondria, whereas mitochondrial deformation and swelling were observed in the absence of glucose. According to this study, the primary metabolic pathway of TMJ disc cells is glycolysis. It was concluded that hypoxic conditions and normal glucose concentrations are needed for the growth of TMJ disc cells. Glucose is necessary to ensure cell survival, extracellular matrix synthesis and mitochondrial function. Glucose deficiency may be related to disc degeneration, aging and disease mechanisms.