Sulforaphane suppresses EMT and metastasis in human lung cancer through miR-616-5p-mediated GSK3ß/ß-catenin signaling pathways.

Sulforaphane is a common antioxidant selectively abundant in cruciferous plants, which exhibits effective anti-cancer actions in control of tumorigenesis or progression of various cancers. A recent study has shown that sulforaphane attenuates the EGFR signaling pathway in non-small cell lung cancer (NSCLC), suggesting its potential anti-metastatic effects. In this study we assessed the involvement of sulforaphane and miR-616-5p in epithelial-mesenchymal transition (EMT) and NSCLC metastasis. Sulforaphane suppressed the cell proliferation in human NSCLC cell lines H1299, 95C and 95D with IC50 values of 9.52±1.23, 9.04±1.90 and 17.35±2.03 µmol/L, respectively. At low concentrations (1-5 µmol/L), sulforaphane dose-dependently inhibited the migration and invasion of 95D and H1299 cells with relatively high metastatic potential. The anti-metastatic action of sulforaphane was confirmed in 95D and H1299 cell xenografts in vivo. In fresh NSCLC tissue samples from 179 patients, miR-616-5p levels were upregulated in late-stage NSCLCs, and strongly correlated with risk of NSCLC recurrence and metastasis. Consistent with the clinic observation, miR-616-5p levels in the 3 NSCLC cell lines were correlated with their metastatic ability, and were decreased by sulforaphane treatment. Silencing miR-616-5p markedly suppressed the migration and invasion of 95D cells in vitro and NSCLC metastasis in vivo. Further studies revealed that miR-616-5p directly targeted GSK3ß and decreased its expression, whereas sulforaphane decreased miR-616-5p levels by histone modification, and followed by inactivation of the GSK3ß/ß-catenin signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in NSCLC cells. Our findings suggest that sulforaphane is a potential adjuvant chemotherapeutic agent for the prevention of NSCLC recurrence and metastasis, and miR-616-5p can be clinically utilized as a biomarker or therapeutic target to inhibit metastasis.

Differential gene expression profile analysis in corticosterone-treated PC12 cells.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder that has been ranked as the 4th leading cause of disability worldwide. Past clinical and laboratory evidence has confirmed that abnormalities of the hypothalamic-pituitary-adrenal (HPA)-axis are involved in MDD development. In this study, we took advantage of corticosterone treatment of PC12 cells as a model to identify genes regulated by HPA-axis hormones. Next-generation RNA-Seq technology was utilized to explore genome-wide differentially expressed gene profiles between control and corticosterone treated PC12 cells. 1,274 genes with at least two-fold expression level change were identified. Gene ontology analysis showed that the top enriched biological processes included response to glucocorticoid signaling, apoptosis, cell division/DNA replication, and neuron projection/axon guidance, highly consistent with phenotypes of PC12 cells treated with corticosterone. Taken together, RNA-seq data is reliable and comprehensive, thus providing a valuable resource for understanding underlying mechanisms of glucocorticoid-induced neuron malfunction.

Histopathological findings in a critically ill patient with avian influenza A (H7N9).

To date, data regarding the pulmonary histopathology of human H7N9 disease are scarce. We herein describe a patient with a severe case of avian influenza A (H7N9). A chest computerized tomography (CT) scan showed diffuse ground-glass opacities and consolidation throughout the lungs. A resection of pulmonary bullae in the right middle lobe was performed by video-assisted thoracic surgery (VATS) based on the extracorporeal membrane oxygenation (ECMO) supportive technique on the 23(rd) day after the onset of symptoms because of a right pneumothorax persistent air leak. The histopathological findings of the resected lung tissue revealed pneumocyte hyperplasia and fibroproliferative changes along with diffuse alveolar damage. Bronchoalveolar lavage fluid (BALF) specimens for influenza A (H7N9) virus were continuously positive for more than three weeks, despite oseltamivir treatment, and continuous viral replication significantly prolonged the course of the disease. The patient's clinical status continuously deteriorated, with the development of refractory hypoxemia due to progressive and rapid lung fibrosis, which was confirmed by the final histological changes observed from a limited post-mortem biopsy of lung tissue. Pre-terminally, he developed multi-organ failure and died on the 39(th) day after symptom onset, despite corticosteroid treatment.