Background: Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non‐small‐cell lung cancer (NSCLC) remains unclear.Methods: Cell counting kit‐8 (CCK‐8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.Results: Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin‐1 (Fer‐1) or knockdown of iron‐responsive element‐binding protein 2 (IREB2) notably weakened curcumin‐induced anti‐tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin‐induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.Conclusion: Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.

Background: Quercetin, a natural flavonoid compound, is a potent cancer therapeutic agent widely found in fruit and vegetables. It has been reported to induce growth inhibition and apoptosis in both A549 and H1299 human lung cancer cells. However, the effect of quercetin‐induced autophagy on apoptosis and the possible autophagy mechanism in A549 and H1299 cells have not yet been critically examined.Methods: A549 and H1299 cells were treated with different concentrations of quercetin for 24 hours. Cell growth was measured by cell counting kit‐8 (CCK‐8) assay, whereas apoptosis was assessed by western blotting analysis of apoptotic proteins. The levels of proteins and genes involved in autophagy were determined by western blotting and reverse transcription polymerase chain reaction (RT‐PCR), respectively. Autophagosomes were also observed by transmission electron microscopy (TEM) and LC3 immunofluorescence.Results: Quercetin inhibited cell viability and induced mitochondria‐dependent apoptosis in both A549 and H1299 cells in a dose‐dependent. Moreover, quercetin also promoted the expression of LC3‐II and beclin 1 and suppressed the expression of p62. The mRNA levels of LC3‐II, beclin 1, Atg5, Atg7, and Atg12 were upregulated by quercetin treatment. Autophagy inhibition with 3‐methyladenine could effectively inhibit quercetin‐induced apoptosis. In addition, quercetin dose‐dependently elevated the levels of SIRT1 protein and the pAMPK–AMPK ratio. Quercetin‐induced autophagy was attenuated by SIRT1 inhibitor EX527 and SirT1 knockdown by small interfering RNA (siRNA).Conclusions: Quercetin‐induced autophagy contributes to apoptosis in A549 and H1299 lung cancer cells, which involved the SIRT1/AMPK signaling pathway.

Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-α in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.

Purpose: The diagnosis and severity of obstructive sleep apnea (OSA) are commonly based on the apnea hypopnea index (AHI). However, patients with similar severity AHIs may show widely varying comorbidities and risks for cardiovascular disease, which may be associated with different severities of nocturnal hypoxia. The percentage of cumulative time with oxygen saturation below 90% in total sleep time (T90) is receiving increasing attention in OSA research because it describes the duration and degree of hypoxia during the whole sleep. This study aimed to explore the distribution of T90 in OSA patients with similar severity and to evaluate the relationship between T90 and hypertension. Patients and Methods: A total of 775 patients with OSA were enrolled in this study, all participants were divided into groups according to the T90 value: light hypoxia (T90≤ 5%), mild hypoxia (T90 accounted for 5– 10%), moderate hypoxia (T90 accounted for 10– 25%), and severe hypoxia (T90> 25%). Multivariate logistic regression analysis was performed to assess the association between T90 and hypertension. Results: Of the patients with mild OSA, 94.33% had light hypoxia, and 88.64% of moderate OSA patients had light hypoxia. The proportions of light, mild, moderate, and severe hypoxia among patients with severe OSA were 28.60%, 17.69%, 21.40%, and 32.31%, respectively. After adjustment for potential confounders, the risk of hypertension in patients with severe OSA increased according to the severity categories of T90. The odds ratio for T90 accounting for 10– 25% relative to T90≤ 5% was 2.544 (95%confidence interval, 1.254– 5.164; P=0.010) and as high as 2.692 (95%confidence interval, 1.403– 5.166; P=0.003) in patients with T90> 25%. Conclusion: OSA patients with similar degree of AHI may have different T90 values, especially in severe OSA. A higher T90 was independently associated with the risk of hypertension after adjustment for traditional risk factors in patients with severe OSA. Our findings highlight the potential role for T90 in predicting hypertension in patients severe OSA.

In most countries, nearly 6% of the adults are suffering from chronic obstructive pulmonary disease (COPD), which puts a huge economic burden on the society. Moreover, COPD has been considered as an independent risk factor for pulmonary embolism (PE). In this review, we summarized the existing evidence that demonstrates the associations between COPD exacerbation and PE from various aspects, including epidemiology, pathophysiological changes, risk factors, clinical features, management, and prognosis. We searched the terms "chronic obstructive pulmonary disease," "pulmonary embolism," "exacerbations," and "thromboembolic" in PubMed database and collected the results up to April 2018. The language was limited to English. We thoroughly examined the titles and abstracts of all studies that met our search strategy. The data from prospective studies, meta-analyses, retrospective studies, and recent reviews were selected for preparing this review. The prevalence of PE in patients with COPD exacerbation varied a lot among different studies, mainly due to the variations in race, sample size, study design, research setting, and enrollment criteria. Overall, whites and African Americans showed significantly higher prevalence of PE than Asian people, and the hospitalized patients showed higher prevalence of PE compared to those who were evaluated in emergency department. PE is easily overlooked in patients with COPD exacerbation due to the similar clinical symptoms. However, several factors have been identified to contribute to the increased risk of PE during COPD exacerbation. Obesity and lower limb asymmetry were described as independent predictors for PE. Moreover, due to the high risk of PE, thromboprophylaxis has been used as an important treatment for hospitalized patients with COPD exacerbation. According to the previous studies, COPD patients with PE experienced an increased risk of death and prolonged length of hospital stay. Therefore, the thromboembolic risk in patients with acute exacerbation of COPD, especially in the hospitalized patients, should carefully be evaluated.

Treatment-emergent central sleep apnea (TECSA) is a specific form of sleep-disordered breathing, characterized by the emergence or persistence of central apneas during treatment for obstructive sleep apnea. The purpose of this review was to summarize the definition, epidemiology, potential mechanisms, clinical characteristics, and treatment of TECSA. We searched for relevant articles up to January 31, 2020, in the PubMed database. The prevalence of TECSA varied widely in different studies. The potential mechanisms leading to TECSA included ventilatory control instability, low arousal threshold, activation of lung stretch receptors, and prolonged circulation time. TECSA may be a self-limited disorder in some patients and could be resolved spontaneously over time with ongoing treatment of continuous positive airway pressure (CPAP). However, central apneas persist even with the regular CPAP therapy in some patients, and new treatment approaches such as adaptive servo-ventilation may be necessary. We concluded that several questions regarding TECSA remain, despite the findings of many studies, and it is necessary to carry out large surveys with basic scientific design and clinical trials for TECSA to clarify these irregularities. Further, it will be vital to evaluate the baseline demographic and polysomnographic data of TECSA patients more carefully and comprehensively.