One concern to the patients is the off-line detection of pneumonia infection status after using the ventilator in the intensive care unit. Hence, machine learning methods for ventilator-associated pneumonia (VAP) rapid diagnose are proposed. A popular device, Cyranose 320 e-nose, is usually used in research on lung disease, which is a highly integrated system and sensor comprising 32 array using polymer and carbon black materials. In this study, a total of 24 subjects were involved, including 12 subjects who are infected with pneumonia, and the rest are non-infected. Three layers of back propagation artificial neural network and support vector machine (SVM) methods were applied to patients’ data to predict whether they are infected with VAP with Pseudomonas aeruginosa infection. Furthermore, in order to improve the accuracy and the generalization of the prediction models, the ensemble neural networks (ENN) method was applied. In this study, ENN and SVM prediction models were trained and tested. In order to evaluate the models’ performance, a fivefold cross-validation method was applied. The results showed that both ENN and SVM models have high recognition rates of VAP with Pseudomonas aeruginosa infection, with 0.9479 ± 0.0135 and 0.8686 ± 0.0422 accuracies, 0.9714 ± 0.0131, 0.9250 ± 0.0423 sensitivities, and 0.9288 ± 0.0306, 0.8639 ± 0.0276 positive predictive values, respectively. The ENN model showed better performance compared to SVM in the recognition of VAP with Pseudomonas aeruginosa infection. The areas under the receiver operating characteristic curve of the two models were 0.9842 ± 0.0058 and 0.9410 ± 0.0301, respectively, showing that both models are very stable and accurate classifiers. This study aims to assist the physician in providing a scientific and effective reference for performing early detection in Pseudomonas aeruginosa infection or other diseases.

In the present study, we explore the role of apoptosis signal-regulating kinase 1 (ASK1) in denbinobin-induced apoptosis in human lung adenocarcinoma (A549) cells. Denbinobin-induced cell apoptosis was attenuated by an ASK1 dominant-negative mutant (ASK1DN), two antioxidants (N-acetyl-L-cysteine (NAC) and glutathione (GSH)), a c-Jun N-terminal kinase (JNK) inhibitor (SP600125), and an activator protein-1 (AP-1) inhibitor (curcumin). Treatment of A549 cells with denbinobin caused increases in ASK1 activity and reactive oxygen species (ROS) production, and these effects were inhibited by NAC and GSH. Stimulation of A549 cells with denbinobin caused JNK activation; this effect was markedly inhibited by NAC, GSH, and ASK1DN. Denbinobin induced c-Jun phosphorylation, the formation of an AP-1-specific DNA-protein complex, and Bim expression. Bim knockdown using a bim short interfering RNA strategy also reduced denbinobin-induced A549 cell apoptosis. The denbinobin-mediated increases in c-Jun phosphorylation and Bim expression were inhibited by NAC, GSH, SP600125, ASK1DN, JNK1DN, and JNK2DN. These results suggest that denbinobin might activate ASK1 through ROS production to cause JNK/AP-1 activation, which in turn induces Bim expression, and ultimately results in A549 cell apoptosis.

The present study investigated the potential of biochanin A, a phytoestrogenic isoflavone of red clover (Triflolium pratense), for use in treating asthma or chronic obstructive pulmonary disease (COPD). Biochanin A (100 μmol/kg, orally (p.o.)) significantly attenuated airway resistance (R_L), enhanced pause (P_enh), and increased lung dynamic compliance (C_dyn) values induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed an increase in the number of total inflammatory cells, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)‐2, IL‐4, IL‐5, and tumor necrosis factor (TNF)‐αin bronchoalveolar lavage fluid (BALF) of the mice. However, it did not influence interferon (IFN)‐γlevels. Biochanin A (100 μmol/kg, p.o.) also significantly suppressed the total and ovalbumin (OVA)‐specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the total IgG_2alevel in the serum of these mice. The PDE4_H/PDE4_Lvalue of biochanin A was calculated as >35. Biochanin A did not influence xylazine/ketamine‐induced anesthesia. Biochanin A (10~30 μM) significantly reduced cumulative OVA (10~100 μg/mL)‐induced contractions in the isolated guinea pig trachealis, suggesting that it inhibits degranulation of mast cells. In conclusion, red clover containing biochanin A has the potential for treating allergic asthma and COPD.

In idiopathic pulmonary fibrosis, the interaction of CXCL12 and CXC receptor 4 (CXCR4) plays a critical role in lung fibrosis. Connective tissue growth factor (CTGF) overexpression underlies the development of pulmonary fibrosis. Our previous report showed that the Rac1-dependent extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein (AP)-1 pathways are involved in CXCL12-generated CTGF expression in human lung fibroblasts (WI-38). In present study, we additionally inspected the involvement of mitogen-activated protein kinase kinase kinase 1 (MEKK1)/JNK-dependent SMAD3 in CXCL12-triggered CTGF expression in WI-38 cells. WI-38 cells were stimulated with CXCL12 in the absence or presence of specific inhibitors or small interfering RNAs (siRNAs). CTGF expression and signaling transduction molecules were assessed by Western blot, luciferase activity assay, or ChIP assay. CXCL-12-induced CTGF expression was attenuated by SIS3 (a SMAD3 inhibitor) and SMAD3 siRNA, but not by SB431542 (an activin receptor-like kinase 5, ALK5, inhibitor). CXCL12-stimulated CTGF expression was also attenuated by MEKK1 siRNA. Treatment of cells with CXCL12 caused an increase in SMAD3 phosphorylation at Ser208, translocation to nuclei, SMAD3-luciferase activity, and recruitment of SMAD3 to the CTGF promoter. Stimulation of cells with CXCL12 resulted in increase in JNK phosphorylation at Thr183/Tyr185 and MEKK1 phosphorylation at Thr261. Moreover, CXCL12-mediated SMAD3 phosphorylation or SMAD3-luciferase activity was inhibited by MEKK1 siRNA or SP600125. Finally, CXCL12-mediated JNK phosphorylation was attenuated by MEKK1 siRNA. In conclusion, results of this study suggest that CXCL12 activates the MEKK1/JNK signaling pathway, which in turn initiates SMAD3 phosphorylation, its translocation to nuclei, and recruitment of SMAD3 to the CTGF promoter, which ultimately induces CTGF expression in human lung fibroblasts.