ABSTRACT
@#Objective To investigate the characteristic volatile organic compounds (VOCs) in exhaled breath and their diagnostic value in patients with early stage lung cancer. Methods Solid-phase micro-extraction combined with gas chromatography mass spectrometry was used to analyze exhaled breath VOCs of 117 patients with early stage lung cancer (54 males and 63 females, with an average age of 61.9±6.8 years) and 130 healthy subjects (79 males and 51 females, with an average age of 63.3±6.6 years. The characteristic VOCs of early stage lung cancer were identified, and a diagnostic model was established. Results Ten characteristic VOCs of early stage lung cancer were identified, including acetic acid, n-butanol, dimethylsilanol, toluene, 2,3,4-trimethylheptane, 3,4-dimethylbenzoic acid, 5-methyl-3-hexene-2-ketone, n-hexanol, methyl 2-oxoglutarate and 4-methoxyphenol. Gender and the 10 characteristic VOCs were included in the diagnostic model, with a sensitivity of 83.8% and a specificity of 96.2%. Conclusion Analysis of exhaled breath VOCs is expected to be one of the potential methods used for early stage lung cancer diagnosis.
ABSTRACT
Atherosclerosis is a complex chronic inflammatory disease that is characterized by the formation of lipid-rich plaques on the inner walls of the arteries. Inactive rhomboid protein 2 (iRhom2) was recently determined as a necessary regulator for the shedding of tumor necrosis factor-alpha (TNF-α) in immune cells. In the present study, we aimed to explore the effects of iRhom2 on the inflammatory response and oxidative stress induced by low-density lipoprotein (ox-LDL) in RAW264.7 and THP-1-derived macrophages. The expression levels of iRhom2 were also investigated in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet (HFD). iRhom2 was significantly induced by ox-LDL in macrophages, as confirmed by Western blotting and RT-qPCR analysis. Furthermore, iRhom2 knockdown showed significant suppressive effects on the activation of ox-LDL-induced RAW264.7 and THP-1-derived macrophages through reducing TACE and TNFR2 expressions, and the inactivation of the IκBα/NF-κB signaling pathway. A reduction in reactive oxygen species (ROS) generation, malondialdehyde (MDA) levels, and nitric oxide (NOX) activity and an increase in glutathione peroxidase (GSH-Px) activity were determined in the absence of iRhom2 expression. In addition, the NF-E2 related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) pathway was also upregulated in ox-LDL-treated macrophages subjected to iRhom2 inhibition. Moreover, suppression of iRhom2 expression inactivated PI3K/AKT pathway activation, contributing to ROS reduction in ox-LDL-stimulated macrophages. iRhom2 was also significantly expressed in ApoE-/- mice fed HFD. Finally, we observed increased serum levels of TNF-α, TNFR1, and TNFR2 in patients with coronary artery atherosclerosis as compared to healthy volunteers. In conclusion, our findings suggested that iRhom2 played a key role in the pathogenesis of atherosclerosis, and that iRhom2 might be a potential therapeutic target against atherosclerosis.
