Comprehensive network analysis to identify the molecular pathogenesis of pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PAH) is a chronic progressive disease that may lead to right heart failure and eventually death. At present, great progress had been achieved in the treatment of pulmonary hypertension. However, pulmonary hypertension cannot be fundamentally cured, and its pathogenesis is still unclear. METHODS: A multifactor-driven dysfunction module of pulmonary hypertension has been constructed in order to explore its potential pathogenesis. We performed differential expression analysis, coexpression analysis, enrichment analysis and hypergeometric test to calculate the potential regulatory effects of multiple factors on the module. RESULTS: Four modules and corresponding hub genes were identified. In addition, we also obtained a series of ncRNA (MALAT1 and miR-17-5p) and transcription factor (HIF1A). Network analysis revealed that MALAT1, NFKB1 and RELA targeting IL1B of module 4 and IL6 of module 1 to participate in the occurrence and development of pulmonary hypertension through Toll-like receptor signaling pathway. CONCLUSIONS: It is necessary to identify disease-related disorders by integrating multiple regulatory factors. The regulatory network may play an important role in PAH. The results not only provided new methods and ideas for follow-up research, but also helps researchers to have a deeper understanding of potential pathogenesis for PAH.

Investigation of the anti­asthmatic activity of Oridonin on a mouse model of asthma.

Oridonin is an extract obtained from a traditional Chinese medicinal herb, Xihuangcao. Previous studies have demonstrated that Oridonin exerts various pharmaceutical effects, such as anti­tumor and immunosuppressive effects, as well as modulating cytokine balance. The present study identified that Oridonin could regulate the Th1/Th2 cytokine balance in mice. However, as the anti­asthmatic effect of Oridonin is currently unknown a mouse model of asthma was used in the present study. BALB/c mice were sensitized using ovalbumin (OVA), then the sensitized mice were treated with Oridonin prior to OVA challenge. The in vivo study indicated that Oridonin decreased the OVA­induced airway hyper­responsiveness significantly (P<0.05). In addition, the results indicated that in Oridonin­treated mice, the eosinophil number and total inflammatory cell number in bronchoalveolar lavage (BAL) fluid decreased significantly in the Oridonin group when compared with the control group. Further study indicated that Oridonin significantly decreased the level of inflammatory cytokines, which were induced by OVA, in BAL fluid. Histological studies were performed to evaluate the effect of Oridonin on eosinophilia and mucus in the airway, the results indicated that Oridonin significantly inhibited the eosinophilia and mucus production in the lungs. Therefore the present study demonstrated that Oridonin regulates Th1/Th2 balance in mice and exhibited anti­asthmatic effects in a mouse model of asthma. These findings indicate that Oridonin may serve as a potential therapeutic compound for the treatment of asthma in future.

Expression of aquaporins in the lungs of mice with acute injury caused by LPS treatment.

The aim of the present study was to investigate the expression of aquaporin 1 (AQP1) and AQP5 in the lungs of mice with acute injury induced by LPS treatment. In the study, the concentrations of cytokines were all significantly increased in the BALF of mice received LPS at 12h and 24h (P<0.001). The lung wet/dry weight ratios (W/D) and total protein content in BALF were also increased in the mice treated with LPS (P<0.001). Interestingly the expression of AQP1 and AQP5 was significantly decreased (P<0.05) compared with these in the control mice, while TUNEL positive cells were increased. However, the AQP5 expression was significantly higher at 24h that it at 12h in the control mice. Our results showed that decreased AQP expression was associated with the increased inflammatory factors, as well as apoptotic cells. The increased expression of AQP5 at 24h in control mice might be due to its regulation in transcellular water reabsorption.