Almonertinib, a new third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective to EGFR T790M-mutant non-small cell lung cancer (NSCLC). However, there is no available information on the form and molecular mechanism of Almonertinib-induced death in NSCLC cells. Herein, CCK-8 and colony formation assays, flow cytometry, electron microscopy, and western blots assay showed that Almonertinib inhibited NSCLC cells growth and proliferation by inducing apoptosis and autophagy which can be inhibited by a broad spectrum of caspase inhibitor Z-VAD-fmk or autophagy inhibitor chloroquine. Importantly, Almonertinib-induced autophagy was cytoprotective in NSCLC cells, and the blockade of autophagy improved cell apoptosis. In addition, Almonertinib increased reactive oxygen species (ROS) generation and clearance of ROS through pretreatment with N-acetyl-L-cysteine (NAC) inhibited the decrease of cell viability, apoptosis and increase of LC3-II induced by Almonertinib. The results of Western blot showed that both EGFR activity and downstream signaling pathways were inhibited by Almonertinib. Taken together, these findings indicated that Almonertinib induced apoptosis and autophagy by promoting ROS production in NSCLC cells.
Objective: Primary closure of the common bile duct (CBD) after laparoscopic CBD exploration (LCBDE) is a technical challenge. The present study was performed to evaluate the safety and effectiveness of this surgical method. Methods: This retrospective study of surgical efficacy and safety involved 79 patients who underwent primary CBD closure with a knotless unidirectional barbed suture or traditional T-tube drainage after LCBDE for CBD stones. Results: The average suturing time, operation time, and postoperative hospital stay were significantly shorter in the primary closure group than T-tube group. There were no significant differences in the mean diameter of the CBD, number of stones, or incidence of postoperative complications between the two groups. No patients developed recurrence of CBD stones during the median follow-up of 21.5 months. Conclusions: After LCBDE and intraoperative choledochoscopy, primary closure with knotless unidirectional barbed sutures is a safe and effective therapeutic option for patients with cholelithiasis and concurrent CBD stones. This is especially true when the CBD is dilated more than 8 mm.
Purpose: To investigate the effect of cell division cycle associated 8 (CDCA8) on malignant progression of gastric cancer (GC) cells.
Methods: Short hairpin RNAs (shRNA) were transfected into two gastric cell lines to knock down expression of CDCA8. Transfection efficiency was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Then, Cell Counting Kit 8 and colony formation and Transwell assays were utilized to explore the effect of CDCA8 knockdown on the proliferation, invasion, and migration of GC cells. Flow cytometry was conducted to analyze the effect of CDCA8 knockdown on cell cycle progression and apoptosis. The relationship between CDCA8, epithelial-mesenchymal transition (EMT), and Akt pathway activity was determined by western blot analysis.
Results: Proliferation, invasion, and migration of GC cells were significantly inhibited by CDCA8 knockdown. Knockdown of CDCA8 induced cell cycle arrest in G1 phase and apoptosis, and inhibited EMT and Akt pathway activity.
Conclusion: Knockdown of CDCA8 inhibits GC growth and metastasis in vitro by reducing Akt pathway activity. Thus, this molecule presents a potential strategy for the management of GC.
Acute lung injury refers to the injury of alveolar epithelial cells and pulmonary capillary endothelial cells caused by noncardiac factors. To better combat the disease, there is an urgent need to develop more effective drugs. Sepsis is a syndrome of systemic inflammation caused by infection, and the molecular mechanism by which sepsis induces acute lung injury has not been clearly determined. Bilobalide is a unique component of Ginkgo biloba. Although it has multiple biological functions, its role in sepsis induced acute lung injury needs further study. In this study, we found that bilobalide alleviated cecal ligation and puncture induced acute lung injury. Additionally, bilobalide regulated cecal ligation and puncture induced lung injury through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway. We therefore conclude that bilobalide may be a potential drug for the treatment of sepsis induced acute lung injury.
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