BackgroundThe major characteristic of COPD is systemic inflammation. The parameters such as neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-basophil ratio (EBR) in routine blood test (RBT) are considered to be the underlying biomarkers of inflammation. We hypothesized that the prognosis of patients with COPD can be predicted with RBT.MethodsPatients with COPD in stable stage were enrolled. The RBT, pulmonary function testing (PFT), BODE index, C-reactive protein (CRP), procalcitonin, and erythrocyte sedimentation rate (ESR) were performed at enrollment and every follow-up once in every 3 months during the 24-month follow-up period. Meanwhile, exacerbation count and mortality incidence were recorded. The correlation between the prognostic biomarkers and the prognosis of patients was analyzed.ResultsThe NLR and EBR in RBT have a significant correlation with the severity of patients with COPD. The NLR is an independent predictor for mortality and the EBR is an independent predictor for exacerbation.ConclusionAs an inexpensive, accessible, and convenient assay, RBT may be used as a practical means in the prediction of prognosis of patients with COPD in future clinical settings.

Taken together, Angptl4 modulates vascular permeability, angiogenesis, inflammatory signaling, and associated diseases. The use of Angptl4-modulating agents such as certain drugs, food constituents (such as fatty acids), nuclear factor (such as PPARα), and bacteria may treat associated diseases such as tumor metastasis, ischemic-reperfusion injury, inflammation, and chronic low-grade inflammation. However, the diverse physiological functions of Angptl4 in different tissues can lead to potentially deleterious side effects when used as a therapeutic target. In this regard, a better understanding of the underlying mechanisms for Angptl4 in different tissues is necessary.

The Amur ide (Leuciscus waleckii) is a cyprinid fish that is widely distributed in Northeast Asia. The Lake Dali Nur population inhabits one of the most extreme aquatic environments on Earth, with an alkalinity up to 50 mmol/L (pH 9.6), thus providing an exceptional model with which to characterize the mechanisms of genomic evolution underlying adaptation to extreme environments. Here, we developed the reference genome assembly for L. waleckii from Lake Dali Nur. Intriguingly, we identified unusual expanded long terminal repeats (LTRs) with higher nucleotide substitution rates than in many other teleosts, suggesting their more recent insertion into the L. waleckii genome. We also identified expansions in genes encoding egg coat proteins and natriuretic peptide receptors, possibly underlying the adaptation to extreme environmental stress. We further sequenced the genomes of 10 additional individuals from freshwater and 18 from Lake Dali Nur populations, and we detected a total of 7.6 million SNPs from both populations. In a genome scan and comparison of these two populations, we identified a set of genomic regions under selective sweeps that harbor genes involved in ion homoeostasis, acid-base regulation, unfolded protein response, reactive oxygen species elimination, and urea excretion. Our findings provide comprehensive insight into the genomic mechanisms of teleost fish that underlie their adaptation to extreme alkaline environments.

Studies have suggested that bone marrow-derived mesenchymal stem cells (MSCs) may be used as a tool for gene therapy. Developmental endothelial locus-1 (Del-1) is a critical factor for cell migration and infiltration via the inhibition of the function of a major leukocyte adhesion receptor LFA-1 which prevents leukocyte adhesion to the endothelium. In the present study, we hypothesized that MSC-based Del-1 gene therapy may have potential therapeutic applications for lipopolysaccharide (LPS)-induced lung injury. The MSCs in the present assay were isolated from 6 week-old male mice. In order to investigate the therapeutic effect of the Del-1 gene on LPS-induced ALI mice, a lentivirus vector containing the Del-1 gene was constructed and transduced into the MSCs. In the in vivo assay, we induced lung injury with LPS injection and treated mice with different groups of MSCs, and compared with groups treated with MSCs alone, we observed that the administration with MSCs carrying Del-1 (MSCs-Del1) markedly alleviated the LPS-induced lung injury. There were significant decreases in the number of neutrophils in bronchoalveolar lavage (BAL) and the serum levels of TNF-α and IL-6 in the Del-1-expressed MSC-treated mice. Furthermore, compared with MSCs treated alone, Del1-MSC-treated mice also exhibited low lung injury scores, high protein concentrations and myeloperoxidase activity. In conclusion, treatment with Del-1-expressed MSCs significantly decreases the severity of endotoxin-induced acute lung injury and the level of inflammatory cytokines in mice.

Lung inflammation and alveolar epithelial cell death are critical events in the development and progression of acute lung injury (ALI). Although angiopoietin-like protein 4 (ANGPTL4) participates in inflammation, whether it plays important roles in ALI and alveolar epithelial cell inflammatory injury remains unclear. We therefore investigated the role of angptl4 in lipopolysaccharide (LPS)-induced ALI and the associated mechanisms. Lentivirus-mediated short interfering RNA targeted to the mouse angptl4 gene (AngsiRNA) and a negative control lentivirus (NCsiRNA) were intranasally administered to mice. Lung inflammatory injury and the underlying mechanisms for regulation of angptl4 on the LPS-induced ALI were subsequently determined. We reported that angptl4 levels were increased both in human alveolar epithelial A549 cells and lung tissues obtained from a mouse model of LPS-induced ALI. Angptl4 expression was induced by LPS in alveolar epithelial cells, whereas LPS-induced lung inflammation (neutrophils infiltration in the lung tissues, tumor necrosis factor α, interleukin 6), lung permeability (lung wet/dry weight ratio and bronchoalveolar lavage fluid (BALF) protein concentration), tissue damage (caspase3 activation), and mortality rates were attenuated in AngsiRNA-treated mice. The inflammatory reaction (tumor necrosis factor α, interleukin 6) and apoptosis rates were reduced in AngsiRNA(h)-treated A549 cells. Moreover, angptl4 promoted NF-kBp65 expression and suppressed SIRT1 expression both in mouse lungs and A549 cells. Additionally, SIRT1 antagonist nicotinamide (NAM) attenuated the inhibitory effects of AngsiRNA both on LPS-induced NF-kBp65 expression and IL6 expression. These findings suggest that silencing angptl4 protects against LPS-induced ALI via regulating SIRT1/NF-kB signaling pathway.

Flow of an electrically conducting fluid in a toroidal duct of square cross-section is analysed. The flow is driven by the azimuthal Lorentz force resulting from the interaction between the radial electric currents created by the difference of electric potential maintained between the cylinder walls and the strong magnetic field imposed in the axial direction. The flow geometry and the value of the Hartmann number correspond to the experiment of Moresco & Alboussière (J. Fluid Mech., vol. 504, 2004, pp. 167-181). The purpose of the analysis is to reveal the flow features at Reynolds numbers below the threshold of transition to turbulence in Hartmann layers. We find that the flow experiences a complex evolution. The laminar base flow experiences the first instability at the Reynolds number significantly smaller than that of the threshold. The instability is axisymmetric and oscillatory. Turbulence appears at a slightly higher Reynolds number. Right up to the Hartmann layer instability, the turbulence remains localized in a layer near the outer cylinder wall. It is demonstrated that the turbulence may affect the transition in the Hartmann layers via unsteady forcing of the outer flow.

Single Ig IL-1 receptor-related molecule (SIGIRR) is one of the members of the Toll-like receptor (TLR)-IL-1 receptor superfamily. Previous studies demonstrated that SIGIRR can function as a negative regulator of IL-1 and LPS signaling. The purpose of this study was to evaluate the effect of enhanced expression of SIGIRR on LPS-induced acute lung injury. We constructed a recombinant adenoviral vector expressing murine SIGIRR (Ad.mSIGIRR) and a control adenoviral vector containing no transgene (Ad.V). A total of 4 × 10⁷ plaque-forming units of Ad.mSIGIRR or Ad.V adenoviral vector were administered intranasally to BALB/c mice. Forty-eight hours later, all the mice were administered a single dose of LPS via i.p. injection to induce lung injury. Lungs and blood were harvested at several time points. The expression of SIGIRR in lung, the histological changes in the lung, the levels of TNF-α in serum and lung, the concentration of nitric monoxide (NO) in lung, and the activity of myeloperoxidase and nuclear transcription factor κB in the lung were examined. A second cohort of mice was followed for survival for 7 days. Administration of Ad.mSIGIRR increased the expression of SIGIRR in lung tissue, as determined by reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. Administration of Ad.mSIGIRR significantly suppressed the inflammatory reaction to LPS, attenuated the lung pathological changes, and improved the survival of mice, relative to a control adenovirus. These findings suggest that modulating the expression level of SIGIRR may be a promising potential treatment for acute lung injury.

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