Hypoxia protects human lung microvascular endothelial and epithelial-like cells against oxygen toxicity: role of phosphatidylinositol 3-kinase. | LitMetric
Hypoxic preconditioning is protective against oxidant-related damage in various organs, such as the heart. We previously showed that rats exposed to hypoxia also exhibit resistance to lethal pulmonary oxygen toxicity. The underlying mechanism and whether similar preconditioning is applicable to cellular models is unknown. In the present study, it was found that hypoxic pre-exposure induces a significant protective effect against hyperoxia-induced cell death in human lung microvascular endothelial cells (HLMVECs) and epithelial type II-like A549 cells. This effect of hypoxia is mediated by the phosphatidylinositol 3-kinase (PI3-K) signaling pathway because the presence of the PI3-K inhibitors, LY294002 and wortmannin, during pre-exposure to hypoxia completely blocks subsequent protection. Further, the hypoxia-dependent protection from hyperoxia was found to be associated with a 2-fold increase in PI3-K activity in hypoxia. Transient overexpression of a catalytically active class IA PI3-K p110alpha isoform also enhanced survival of A549 cells 2-fold compared with the empty vector control. These results indicate that hypoxia-induced activation of PI3-K is an important event in the acquisition of resistance against subsequent hyperoxic toxicity.
In many clinical contexts, the event of interest could occur multiple times for the same patient. Considerable advancement has been made on developing recurrent event models based on or that use biomarker information. However, less attention has been given to evaluating the prognostic accuracy of a biomarker or a composite score obtained from a fitted recurrent event-rate model.
Background: Computational modeling indicated that pathological high shear stress (HSS; 100 dyn/cm) is generated in pulmonary arteries (PAs; 100-500 µm) in congenital heart defects causing PA hypertension (PAH) and in idiopathic PAH with occlusive vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is a feature of PAH. We hypothesize that HSS induces EndMT, contributing to the initiation and progression of PAH.
Aim: Intraoperative lung-protective ventilation strategies (LPVS) have been shown to improve lung oxygenation and prevent postoperative pulmonary problems in surgical patients. However, the application of positive end-expiratory pressure (PEEP)-based LPVS in emergency traumatic brain injury (TBI) has not been thoroughly explored. The purpose of this study is to evaluate the effects of drive pressure-guided individualized PEEP on perioperative pulmonary oxygenation, postoperative pulmonary complications, and recovery from neurological injury in patients with TBI.
Aim: The prognostic factors and a nomogram applicable to breast cancer (BC) patients with bone metastasis (BM) who received first-line chemotherapy have not been extensively studied. This study aimed to identify prognostic factors and construct a prognostic nomogram to predict overall survival (OS) in this population.
Methods: Data for BC patients with BM undergoing first-line chemotherapy were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016.
There are many causes of peripheral blood eosinophilia (PBE), including allergic, infectious, rheumatic, and hematologic disorders. Solid tumor cancers, such as lung cancer, can also cause PBE, and although rare, being diagnosed with PBE in this way is associated with a worse prognosis than for lung cancer patients without PBE. Additionally, some cancer patients develop PBE when receiving treatment with immune checkpoint inhibitors (ICIs).
