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Objective: We explored whether hyperlipidemia or combination of hyperlipidemia and E2 could induce TMJOA. Materials and Methods: Four groups of female rats were treated with normal diet, normal diet with E2, high‐fat diet, and high‐fat diet with E2 (HFD/E2), respectively, to induce TMJOA till 8 weeks. Another three groups were then used for COX2 inhibitor celecoxib to block the induction of TMJOA. Primary condylar chondrocytes were treated with combination of E2, ox‐LDL, and corresponding inhibitors for evaluating expressions of related molecules. Results: Condylar cartilage proliferation with plenty of chondrocyte apoptosis and increased staining for LOX1, nuclear NF‐κB, IL‐1β, and COX2 at 4 weeks and decreased condylar cartilage and increased subchondral bone density at 8 weeks were observed only in the HFD/E2 group. Celecoxib significantly alleviated the cartilage proliferation and apoptosis in the HFD/E2 group. Serum ox‐LDL increased in both high‐fat diet groups, while serum IL‐1β increased only in the HFD/E2 group. Combination of E2 and ox‐LDL synergistically induced expressions of LOX1, phosphorylated NF‐κB, IL‐1β, and COX2, while LOX1 inhibitor blocked the induction of phosphorylated NF‐κB, and NF‐κB inhibitor the induction of IL‐1β, and IL‐1β inhibitor the induction of COX2. Conclusion: Combination of hyperlipidemia and E2‐induced TMJOA‐like pathological changes through LOX1/NF‐κB/IL‐1β/COX2‐signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore whether knockdown of cancer‐derived IgG (CIgG) could enhance cisplatin‐induced anti‐cancer effects. Materials and methods: Cancer‐derived IgG was knocked down by siRNA or Tet‐on shRNA in the absence or presence of cisplatin in WSU‐HN6 or CAL27 cells. Cell proliferation, apoptosis, and mobility were evaluated using CCK‐8, flow cytometry, and transwell assays, respectively. Molecular events were investigated using real‐time PCR and Western blot assays. Results: Knockdown of CIgG significantly promoted cisplatin‐induced apoptosis and inhibition of cell proliferation, migration, and invasion. Cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1, while knockdown of CIgG downregulated phosphorylation of AKT and PDK1, and blocked cisplatin‐induced upregulation of AKT and PDK1 phosphorylation. Moreover, knockdown of CIgG blocked cisplatin‐induced upregulation of Src phosphorylation, and knockdown of Src blocked cisplatin‐induced upregulation of AKT and PDK1 phosphorylation. Overexpression of Src upregulated AKT and PDK1 phosphorylation. Furthermore, knockdown of CIgG upregulated PTP‐BAS mRNA and protein expression, whereas cisplatin downregulated PTP‐BAS protein, but not mRNA expression; knockdown of PTP‐BAS upregulated phosphorylation of Src, PDK1, AKT, and blocked CIgG knockdown‐mediated enhancement of cisplatin‐induced inhibition of cell proliferation. Conclusion: Knockdown of CIgG enhanced the anti‐cancer effects of cisplatin through PTP‐BAS/Src/PDK1/AKT signaling pathway in oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore whether RhoG/Rac1 was involved in migration and invasion of salivary adenoid cystic carcinoma (SACC). Materials and Methods: RhoG and Rac1 were evaluated in two SACC cell lines, namely SACC‐83 and SACC‐LM, with low and high rates of lung metastasis, respectively. Functional changes were evaluated using cell proliferation, transwell, and wound‐healing assays, and molecular events were investigated using real‐time PCR and Western blot assays. Results: RhoG and Rac1 were highly expressed and more activated in SACC‐LM cells than in SACC‐83 cells. RhoG overexpression promoted SACC‐83 cell migration and invasion through activating Rac1. The knockdown of RhoG or Rac1 partially blocked epiregulin‐induced migration and invasion in SACC‐83 cells. Epiregulin‐induced activation of RhoG/Rac1 in SACC‐83 cells was blocked by a Src inhibitor, or an AKT inhibitor or AKT siRNA, or an ERK1/2 inhibitor. Moreover, the epiregulin‐induced phosphorylation of AKT and ERK1/2 in SACC‐83 cells was blocked by a Src inhibitor, and the epiregulin‐induced phosphorylation of ERK1/2 was blocked by an AKT inhibitor or AKT siRNA. Overexpression of activated AKT induced activation of ERK1/2 and RhoG. Conclusions: RhoG/Rac1 signaling pathway was involved in SACC cell migration and invasion. RhoG/Rac1 at least partially mediated epiregulin/Src/AKT/ERK1/2 signaling to promote SACC cell migration and invasion. [ABSTRACT FROM AUTHOR]