Protective effect of liver X receptor on cigarette smoke and lipopolysaccharide induced airway inflammation and emphysema in mice.

OBJECTIVE: The aim of this study is to assess the impact of Liver X receptors (LXRs) on airway inflammation, airway remodeling, and lipid deposition induced by cigarette smoke and lipopolysaccharide (LPS) exposure in the lung. METHODS: Wild mice and LXR-deficient mice were exposed to cigarette smoke and LPS to induce airway inflammation and remodeling. In addition, some wild mice received intraperitoneal treatment with the LXR agonist GW3965 before exposure to cigarette smoke and LPS. Lung tissue and bronchoalveolar lavage fluid were collected to evaluate airway inflammation, airway remodeling and lipid deposition. RESULTS: Exposure to cigarette smoke and LPS resulted in airway inflammation, emphysema and lipid accumulation in wild mice. These mice also exhibited downregulated LXRα and ABCA1 in the lung. Treatment with GW3965 mitigated inflammation, remodeling and lipid deposition, while the deletion of LXRs exacerbated these effects. Furthermore, GW3965 treatment following exposure to cigarette smoke and LPS increased LXRα and ABCA1 expression and attenuated MyD88 expression in wild mice. CONCLUSION: LXRs demonstrate the potential to mitigate cigarette smoke and LPS- induced airway inflammation, emphysema and lipid disposition in mice.

Role of liver-X-receptors in airway remodeling in mice with chronic allergic asthma.

Liver X receptors (LXRs) exert anti-inflammatory effects in animal models of certain respiratory diseases. In the present study, a model of chronic airway remodeling was established in wild-type and LXR-deficient mice. Ovalbumin (OVA)-sensitized mice were chronically administered OVA via inhalation for 8 weeks. Prior to each stimulation, certain wild-type mice were treated with GW3965, which is a highly selective LXR agonist. The influence of LXRs on airway inflammation, airway hyperresponsiveness and airway remodeling was evaluated. LXRs were indicated to increase airway inflammation and airway hyperresponsiveness, as well as promote airway remodeling. These results suggest that inhibiting LXRs may be a potential method for the treatment of allergic asthma.

Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activities.

In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

Pyruvate kinase M2 activation protects against the proliferation and migration of pulmonary artery smooth muscle cells.

Pyruvate kinase M2 (PKM2), which is encoded by PKM, is a ubiquitously expressed intracellular protein and is associated with proliferation cell phenotype. In PAH patients and PAH models, we found higher levels of PKM2 tyrosine 105 phosphorylation (phospho-PKM2 (Y105)) than in controls, both in vivo and in vitro. Here, we demonstrate that PKM2 stimulates inflammatory and apoptosis signalling pathways in pulmonary artery smooth muscle cells (PASMCs) and promotes PASMC migration and proliferation. PKM2 phosphorylation promoted the dimerization activation and nuclear translocation of STAT3, a transcription factor regulating proliferation, growth, and apoptosis. TLR2, a transmembrane protein receptor involved in both innate and adaptive immune responses, promoted PKM2 phosphorylation in hypoxia-induced PASMCs. Therefore, we hypothesized that PKM2 also affects the proliferation and migration of PASMCs. The proliferation of hypoxia-induced normal human pulmonary artery smooth muscle cells (normal-HPASMCs) was found to be inhibited by TEPP-46 (PKM2 agonist) and PKM2 siRNA using wound healing, 5-ethynyl-2'-deoxyuridine (EdU), and immunofluorescence (Ki67) assays. PASMCs isolated from PAH patients (PAH-HPASMCs) and hypoxia-treated rats (PAH-RPASMCs) also confirmed the above results. TEPP-46 treatment was found to improve hypoxia-induced pulmonary artery remodelling and right heart function in mice, and the link between PKM2 and STAT3 was also confirmed in vivo. In conclusion, PKM2 plays crucial roles in the proliferation and migration of PASMCs.

Lipoprotein-associated phospholipase A2 predicted cardiovascular disease in obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular disease (CVD). As a new inflammatory biomarker of CVD, rare attention has been paid to the roles of lipoprotein-associated phospholipase (Lp-PLA2) in OSAS studies. In this study, we aimed to investigate the correlation between Lp-PLA2 and concomitant CVD in OSAS patients. METHODS: In this prospective study, 152 OSAS patients were further divided into mild, moderate, and severe OSAS subgroups. They presented heart failure, coronary artery disease, or arrhythmia were confirmed with CVD. Thirty-one subjects without OSAS were recruited for the control group. The relationship between Lp-PLA2 and concomitant CVD in OSAS patients was analyzed. RESULTS: Serum Lp-PLA2 values were significantly higher in the severe and moderate OSAS group compared with mild OSAS and OSAS negative groups (P = 0.025). Significant increase was noticed in serum Lp-PLA2 levels in CVD patients compared with those without in severe-moderate-mild OSAS (P < 0.05). In logistic regression analysis, the level of Lp-PLA2 was proved as a significant independent predictor for CVD (OR = 1.117, P = 0.008). The ROC analysis indicated that the best cut-off value of Lp-PLA2 for predicting CVD in OSAS patients was 238.09 ng/ml. The positive and negative predictive values were 72.5% and 70.5%, respectively. The sensitivity was 46.8% and the specificity was 87.8%. CONCLUSIONS: Lp-PLA2 might be associated with the severity of OSAS and the occurrence of CVD in OSAS patients. Lp-PLA2 is expected to be a promising biomarker candidate in predicting CVD in patients with OSAS due to test convenience.

Transformation of external sulphate and its effect on phosphorus mobilization in Lake Moshui, Wuhan, China.

Average concentrations of sulphate in lakes continue to increase sharply. The response of phosphorus to sulphate input is of great importance due to the relationship between eutrophication and ecological health. A four-week experiment was conducted under simulated conditions using samples from a heavily polluted lake, Lake Moshui, in Wuhan, China, to examine the influence of external sulphate on phosphorus release and the transformation of sulphate. The results showed that the diffusion of sulphate into the sediments promoted the proliferation of sulphate-reducing bacteria (SRB) and the reduction of sulphate. Acetic acid was consumed due to sulphate reduction. The soluble reactive phosphorus (SRP) and soluble Fe measured with diffusive equilibration in thin-films (DET) probes increased significantly after the input of sulphate. The content of SRP was consistent with the variation in both the SRB number and the S(0) content in the sediments. The maximum SRP concentration of 100.43 mg L(-1) was recorded 3 cm below the sediment-water interface on the 29th d, which was more than twice the value of the control. There was a positive correlation between concentrations of Fe and SRP in the overlying water and the pore water of the sediments.