Non‑small cell lung cancer (NSCLC) has long been one of the most lethal types of cancer due to its lack of typical clinical symptoms at early stages and high risk of tumour recurrence, even following complete surgical resection. Multicourse chemotherapy based on cisplatin (CDDP) is the standard adjuvant treatment for NSCLC; however, its benefits for the overall survival of patients are limited. In this study, NSCLC cells possessing CDDP‑resistant characteristics (N5CP cells), obtained from surgical resection of clinical specimens of patients with NSCLC, were cultured and screened to generate research models. This study aimed to identify the mechanism underlying tumour cell resistance to CDDP and to identify a novel treatment for NSCLC following CDDP failure. CDDP‑mediated NF‑E2 related factor 2 (Nrf2)/light chain of System xc‑ (xCT) pathway activation was associated with the resistance of cells to CDDP. Therefore, erastin/sorafenib regulation of Nrf2 or xCT expression may alter the sensitivity of tumour cells to CDDP. The small molecules erastin and sorafenib effectively induced N5CP cell ferroptosis, which was mediated by the accumulation of intracellular lipid reactive oxygen species. Additionally, low doses of erastin or sorafenib could be used in association with CDDP to effectively trigger N5CP cell ferroptosis. Furthermore, it was indicated that erastin and sorafenib, alone or in combination with a low dose of CDDP, effectively inhibited the growth of N5CP cells in vivo. Therefore, ferroptosis inducers, including erastin and sorafenib, may be considered a novel treatment regimen for patients with NSCLC, particularly patients with CDDP failure.

Obstructive sleep apnea can induce chronic intermittent hypoxia (CIH) during sleep and is associated with obesity and diabetes. Resveratrol (RSV), a polyphenolic phytoalexin, can regulate glucose metabolism, thereby reducing insulin resistance. The present study aimed to assess whether RSV attenuates CIH‑induced insulin resistance in rats and the underlying mechanisms. A total of 40 rats were randomly assigned into five groups: i) Control; ii) subjected to CIH only; iii) subjected to CIH and treated with 3 mg/kg/day of RSV; iv) subjected to CIH and treated with 30 mg/kg/day of RSV; v) subjected to CIH and treated with 60 mg/kg/day of RSV. All animals were sacrificed following 28 days of treatment. Subsequently, the blood and livers were harvested and blood insulin and glucose levels were measured. Levels of sirtuin (Sirt) 1, insulin receptor (InsR) and glucose transporter 2 (Glut2) in the liver were measured. RSV treatment was demonstrated to suppress weight gain and improve hepatic morphology. RSV treatment also significantly reduced the homeostasis model assessment estimate of insulin resistance of the rats exposed to CIH. This effect occurred in a dose‑dependent manner. RSV significantly upregulated liver Sirt1 levels and inhibited InsR and Glut2 expression in the liver. Additionally, RSV activated the phosphorylation of phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K) and AKT. The present study demonstrates that RSV prevents CIH‑induced insulin resistance in rats. Upregulation of Sirt1 and activation of PI3K/AKT signaling may be involved in this process.

Background: The mechanisms underlying differences in the susceptibility to chronic obstructive pulmonary disease (COPD) exacerbations between patients are not well understood. Recent studies have shown that the patients with frequent COPD exacerbations is related to specific protein expression in lung tissue. Anterior gradient 3 (AGR3) is expressed in airway epithelial cells in the lung and proteomic analysis revealed that its expression is decreased in patients with frequent COPD exacerbations. Moreover, the loss of epithelial integrity might facilitate trans-epithelial permeability of pathogens in such patients. This study was performed to determine that AGR3 protein play a role in COPD frequency exacerbators.Methods: Human lung tissues were collected from current-smoking patients (Control; n = 15) as well as patients with infrequent COPD exacerbations (IFCOPD; n = 18) and frequent COPD exacerbations (FCOPD; n = 8). While AGR3 protein expression was measured by immunohistochemistry and western blotting, AGR mRNA expression was determined by real time quantitative polymerase chain reaction (RT-qPCR). Furthermore, adherent junctions (AJs) and tight junctions (TJs) protein expression in human lung tissues were measured by immunohistochemistry. The effects of cigarette smoke extract (CSE) on AJ and TJ protein and mRNA expression in BEAS-2B cells were assessed by western blotting and RT-qPCR. In addition, the effect of AGR3 overexpression and knockdown on AJ and TJ protein expression was determined.Results: AGR3 was mainly expressed in the airway epithelium and AGR3-positive products were localized in the cytoplasm. Western blotting and RT-qPCR results showed that AGR3 protein (p = 0.009) and mRNA (p = 0.04) expression in the FCOPD group was significantly lower than that in the IFCOPD group. Moreover, E-cadherin, occludin, and zonula occludens-1 (ZO-1) expression was lower in the FCOPD group than in the IFCOPD group. The protein and mRNA expression of E-cadherin, occludin, and ZO-1 was decreased within 24 h post-CSE exposure. AGR3 overexpression rescued CSE-induced downregulation of E-cadherin, occludin, and ZO-1.Conclusion: Difference in AGR3 expression in the lung tissue might be correlated with increased susceptibility to COPD exacerbation. AGR3 can prevent CSE-induced downregulation of E-cadherin, occludin, and ZO-1 in airway epithelial cells. Loss of AGR3 might promote viral and bacterial infection and induce immune inflammation to increase COPD exacerbation.

The pathogenesis of respiratory diseases is complex, and its occurrence and development also involve a series of pathological processes. The present research methods are have difficulty simulating the natural developing state of the disease in the body, and the results cannot reflect the real growth state and function in vivo. The development of microfluidic chip technology provides a technical platform for better research on respiratory diseases. The size of its microchannel can be similar to the space for cell growth in vivo. In addition, organ-on-a-chip can achieve long-term co-cultivation of multiple cells and produce precisely controllable fluid shear force, periodically changing mechanical force, and perfusate with varying solute concentration gradient. To sum up, the chip can be used to analyze the specific pathophysiological changes of organs meticulously, and it is widely used in scientific research on respiratory diseases. The focus of this review is to describe and discuss current studies of artificial respiratory systems based on organ-on-a-chip technology and to summarize their applications in the real world.