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Glutamate and γ‑aminobutyric acid (GABA) transporters serve central roles in normal neuronal activity and are associated with numerous pathological brain conditions, including ischemia and epilepsy. However, the interplay between these transporters in ischemia remains unclear. In the present study, the expression levels of the excitatory amino acid carrier 1 (EAAC1) and GABA transporter 1 (GAT1) were analyzed in vivo and in vitro within ischemic models by immunofluorescence, western blot and RT‑qPCR. Cell survival rates were analyzed following altered expression of these transporters within neuronal cells by flow cytometry. Expression levels of EAAC1 were reduced within the cerebrum of focal cerebral ischemic middle cerebral artery occlusion rat models as well as in primary neurons cultured under hypoxia. However, GAT1 expression levels were slightly elevated under ischemic conditions. The altered expression levels of EAAC1 and GAT1 were combined within neuron cells and the effects were investigated. Apoptotic analysis revealed that EAAC1 suppression and overexpression of GAT1 increased neuronal cell apoptosis under hypoxic conditions; however, EAAC1 overexpression combined with GAT1 knockdown reduced neuronal cell apoptosis under hypoxic conditions. The present study detected the expression levels of the glutamate and GABA transporters under hypoxia, in association with ischemia. The results indicated that, increased expression of EAAC1 combined with GAT1 suppression may provide protective effects in the treatment of epilepsy and ischemia. [ABSTRACT FROM AUTHOR]

Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on certain types of cancer cells. However, the effects of chrysophanol on human breast cancer remain to be elucidated. The aim of the present study was to clarify the role of chrysophanol on breast cancer cell lines MCF‑7 and MDA‑MB‑231, and to identify the signal transduction pathways regulated by chrysophanol. MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited cell proliferation, and cell cycle progression in a dose‑dependent manner. The expression of cell cycle‑associated cyclin D1 and cyclin E were downregulated while p27 expression was upregulated following chrysophanol treatment at the mRNA, and protein levels. The Annexin V/propidium iodide staining assay results revealed that apoptosis levels increased following chrysophanol treatment. Chrysophanol upregulated caspase 3 and poly (ADP‑ribose) polymerase cleavage in both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis regulator Bcl‑2 protein, and transcription factor p65 and IκB phosphorylation. Inhbition of nuclear factor (NF)‑κB by ammonium pyrrolidine dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated proteins. In conclusion, the results of the current study demonstrated that chrysophanol effectively suppresses breast cancer cell proliferation and facilitates chemosentivity through modulation of the NF‑κB signaling pathway. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most debilitating and invasive tumors. Although previous reports have demonstrated the critical role microRNA-181a (miR-181a) serves in the progression of ESCC, how miR-181a induces epithelial-mesenchymal transition (EMT) remains to be elucidated. In the present study, the expression profiles of TGF-β1 and Smad4 proteins in 88 patients with ESCC and 21 adjacent non-cancerous tissues were analyzed using immunohistochemistry. The expression of miR-181a in ESCC cells (ECA109 and TE-1) and HEEC was analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The role of miR-181a in ESCC was analyzed using miR-181a mimics and inhibitor in the same system. Migration, proliferation and apoptosis of cells were assessed using wound-healing assays and cell proliferation assays and flow cytometry, respectively. The expression levels of TGF-β1 and Smad4 in ESCC cell lines transfected with miR-181a mimics and inhibitor were measured using RT-qPCR and western blotting. The expression of E-cadherin and vimentin was also assessed following transfection. The findings demonstrated that expression of TGF-β1 was upregulated, in contrast to Smad4 expression which was downregulated. Expression levels of Smad4 affected the prognosis of patients with ESCC. Higher expression of miR-181a promoted migration and proliferation but inhibited apoptosis of ESCC cells. miR-181a promoted EMT by modulating Smad4 expression in ESCC cells. Overall, these findings revealed that miR-181a induced EMT in ESCC via the TGF-β/Smad pathway in ESCC. Consequently, miR-181a is a potential novel target against ESCC. [ABSTRACT FROM AUTHOR]