Asiatic acid (AA) is a pentacyclic triterpenoid isolated from Centella asiatica (L.) Urban that possesses significant antitumor activities. In the present study, the mechanism of AA on transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) was investigated in the lung cancer cell line A549. To do so, cell morphological alterations were observed and recorded at different time periods. Cells treated with TGF-β1 were spindle-shaped and characterized as stromal cells, whereas AA-treated cells exhibited epithelial cell characteristics and increased intercellular adhesion. The MTT assay demonstrated that the high concentration of AA inhibited the viability of A549 cells treated with TGF-β. In addition, the wound healing and Transwell assays revealed that AA inhibited TGF-β1-induced invasion and migration of A549 cells. Furthermore, AA treatment increased the mRNA and protein expression levels of E-cadherin, and decreased the expression levels of snail family transcriptional repressor (Snail), N-cadherin, vimentin and β-catenin in TGF-β1-treated A549 cells. In conclusion, these results suggested that AA may inhibit TGF-β1-induced EMT in lung cancer through increased expression of E-cadherin, and inhibition of Snail, N-cadherin and vimentin expression.
BackgroundGlaucoma is classified as a neurodegenerative disease. However, the biomarkers of neurodegeneration in the aqueous humour of primary open angle glaucoma (POAG) eyes have not been quantitatively examined yet. In this study, levels of neurodegeneration-related cytokines in the aqueous humour of POAG eyes were measured and compared with those of non-glaucoma (senile cataract) control eyes.MethodsThis cross-sectional study included 24 patients (24 eyes) with POAG and 22 patients (22 eyes) with cataract. Aqueous humour samples were collected before the commencement of phacoemulsification surgery. The concentrations of brain-derived neurotrophic factor (BDNF), cathepsin D, myeloperoxidase (MPO), soluble intercellular adhesion molecule-1 (sICAM-1), soluble neural cell adhesion molecule (sNCAM), soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were measured using the Luminex suspension array technique. The clinical characteristics of the patients were also obtained for correlation analysis.ResultsCompared with the cataract group, the levels of cathepsin D (P < 0.001), sNCAM (P < 0.001) and sVCAM-1 (P = 0.007) were significantly higher in the aqueous humour samples from POAG. The levels of BDNF, sICAM-1, MPO and PAI-1 did not differ among the groups. Mean deviation (MD) values measured by the Humphrey Visual Field Analyzer were significantly associated with levels of cathepsin D (P < 0.001; ρ= − 0.668), sICAM-1 (P = 0.003; ρ= − 0.579), sVCAM-1(P < 0.001; ρ= − 0.695), and PAI-1 (P = 0.007; ρ= − 0.533). The cytokines showed a positive correlation among each other (P < 0.0083).ConclusionThese data suggest that POAG patients had elevated levels of multiple biomarkers of neurodegeneration in the aqueous humour, and these elevated biomarkers may be related to trabecular meshwork injury.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR-OOC-16008516) on May 22, 2016.
MR1T lymphocytes are a recently identified population of T cells that recognize unknown self-antigens presented by the non-polymorphic MHC-I-related molecule, MR1. MR1T cells can kill tumor cells and modulate the functions of other immune cells with promising therapeutic applications. By integrating genetic, pharmacological and biochemical approaches we identified carbonyl stress and alterations of nucleobase metabolism in tumor target cells that promote recognition by MR1 T cells. We dissected these pathways and found that nucleobase adduct-containing metabolites are self-antigens stimulating MR1T cells. Several nucleobase adducts are presented by MR1 molecules and stimulate individual MR1T cells. Our data suggest that MR1T cells are surveyor of cellular metabolic alterations occurring in conditions of metabolic stress, such as cancer, and lay the groundwork for the development of novel HLA-unrestricted T cell-based therapies.
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