Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9 expression in non-small-cell lung cancer by repressing nuclear factor-κB.

The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion. The shRNA was utilized for RNA interference. The target gene and protein expression levels were assessed using reverse transcription-PCR and western blot assay. The DNA-binding activity of nuclear factor κB (NF-κB) was examined using electrophoretic mobility shift assays. Luciferase reporter assay was used to detect the binding of NF-κB to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317 inhibited the invasion and migration of A549 cells in a dose-dependent manner. Meanwhile, we further indicated that activation of LXRß, one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXRß triggered by T0901317 inhibited the invasion and metastasis of A549 cells by repressing NF-κB/MMP-9 signaling pathway. Taken together, our study shows that activation of LXRs triggered by T0901317 inhibits the invasion and metastasis of human non-small-cell lung cancer by repressing the NF-κB/MMP-9 signaling pathway.

Proanthocyanidin from grape seed extract inhibits airway inflammation and remodeling in a murine model of chronic asthma.

Asthma is characterized by airway inflammation and airway remodeling. Our previous study revealed that grape seed proanthocyanidin extract (GSPE) could inhibit asthmatic airway inflammation and airway hyper-responsiveness by down-regulation of inducible nitric oxide synthase in a murine model of acute asthma. The present study aimed to evaluate GSPE's effects on airway inflammation and airway remodeling in a chronic asthmatic model. BALB/c mice were sensitized with ovalbumin (OVA) and then were challenged three times a week for 8 weeks. Airway responsiveness was measured at 24 h after the last OVA challenge. HE staining, PAS staining, and Masson staining were used to observe any airway inflammation in the lung tissue, airway mucus secretion, and subepithelial fibrosis, respectively. The cytokines levels in the lavage fluid (BALF) in addition to the total serum immunoglobulin E (IgE) levels were detected by ELISA. Furthermore, lung collagen contents, α-smooth muscle actin (α-SMA), and transforming growth factor-ß1 (TGF-ß1) expression in the airway were assessed by hydroxyproline assay, immunohistochemistry, and Western blot analysis, respectively. GSPE administration significantly suppressed airway resistance as well as reduced the amount of inflammatory cells, especially the eosinophil count, in BALF. Additionally, the GSPE treatment markedly decreased interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) levels in BALF in addition to the total serum IgE levels. A histological examination demonstrated that GSPE significantly ameliorated allergen-induced lung eosinophilic inflammation and decreased PAS-positive epithelial cells in the airway. The elevated hydroxyproline contents, lung α-SMA contents, and TGF-ß1 protein expression that were observed in the OVA mice were also inhibited by GSPE. In conclusion, GSPE could inhibit airway inflammation and airway remodeling in a murine model of chronic asthma, thus providing a potential treatment for asthma.

[Clinical analysis of the rare causes of hemoptysis: a report of 4 cases].

OBJECTIVE: To improve the diagnosis of hemoptysis caused by rare lung diseases. METHODS: Four cases of hemoptysis caused by rare diseases which were diagnosed by angiography or operation were reported and related literature were reviewed. RESULTS: The 4 cases of hemoptysis were caused by intercostal-to-pulmonary arterial fistula (IPAF), pulmonary hamartoma (PH), congenital unilateral absence of the left pulmonary artery (ALPA) and primary pulmonary hypertension (PPH). Bronchial arteriography and bronchial artery embolization were performed for IPAF. For PH, a benign tumor, the diagnosis was based on the history and radiography examination, and operation was the choice for therapy. ALPA was confirmed by radiography, if massive hemoptysis occurred, surgical intervention was the best choice. The diagnosis of PPH was firstly evaluated by chest film and echocardiogram, and the final diagnosis relied on right cardiac catheter examination. CONCLUSIONS: Hemoptysis is a common symptom of respiratory diseases, including some rare cases which are easy to be misdiagnosed. The correct diagnosis and therapy rely on comprehensive thinking, careful history collection and reasonable examinations.