Autoantibodies of inflammatory cytokines as serum biomarkers in OSA patients.

As many as 90% of patients with obstructive sleep apnea (OSA) may be undiagnosed. It is necessary to explore the potential value of autoantibodies against CRP, IL-6, IL-8 and TNF-α in the diagnosis of OSA. ELISA was performed to detect the level of autoantibodies against CRP, IL-6, IL-8 and TNF-α in sera from 264 OSA patients and 231 normal controls (NCs). The expression level of autoantibodies against CRP, IL-6 and IL-8 in OSA were significantly higher than that in NC while the level of anti-TNF-α was lower in OSA than that in NC. The per SD increment of anti-CRP, anti-IL-6 and anti-IL-8 autoantibodies were significantly associated with a 430%, 100% and 31% higher risk for OSA, respectively. The AUC of anti-CRP was 0.808 (95% CI: 0.771-0.845) when comparing OSA with NC, while the AUC increased to 0.876 (95% CI: 0.846-0.906) combining four autoantibodies. For discrimination of severe OSA versus NC and non-severe OSA versus NC, the AUC for four autoantibodies combination was 0.885 (95% CI: 0.851-0.918) and 0.876 (95% CI: 0.842-0.913). This study revealed the association between autoantibodies against inflammatory factors and OSA, and the combination of autoantibodies against CRP, IL-6, IL-8 and TNF-α may function as novel biomarker for monitoring the presence of OSA.

Characteristics of atmospheric non-methane hydrocarbons during haze episode in Beijing, China.

This study firstly focused on non-methane hydrocarbons (NMHCs) during three successive days with haze episode (16-18 August 2006) in Beijing. Concentrations of alkanes, alkenes, aromatic hydrocarbons, and ethyne all peaked at traffic rush hour, implying vehicular emission; and alkanes also peaked at non-traffic rush hour in the daytime, implying additional source. Especially, alkanes and aromatics clearly showed higher levels in the nighttime than that in the daytime, implying their active photochemical reactions in the daytime. Correlation coefficients (R (2)) showed that propane, n-butane, i-butane, ethene, propene, and benzene correlated with ethyne (R (2) = 0.61-0.66), suggesting that their main source is vehicular emission; 2-methylpentane and n-hexane correlated with i-pentane (R (2) = 0.61-0.64), suggesting that gasoline evaporation is their main source; and ethylbezene, m-/p-xylene, and o-xylene correlated with toluene (R (2) = 0.60-0.79), suggesting that their main source is similar to that of toluene (e.g., solvent usage). The R (2) of ethyne, i-pentane, and toluene with total NMHCs were 0.58, 0.76, and 0.60, respectively, indicating that ambient hydrocarbons are associated with vehicular emission, gasoline evaporation, and solvent usage. The sources of other hydrocarbons (e.g., ethane) might be natural gas leakage, biogenic emission, or long-range transport of air pollutants. Measured higher mean B/T ratio (0.78 ± 0.27) was caused by the more intensive photochemical activity of toluene than benzene, still indicating the dominant emission from vehicles.

Size distributions and sources of elements in particulate matter at curbside, urban and rural sites in Beijing.

Size distributions of 29 elements in aerosols collected at urban, rural and curbside sites in Beijing were studied. High levels of Mn, Ni, As, Cd and Pb indicate the pollution of toxic heavy metals cannot be neglected in Beijing. Principal component analysis (PCA) indicates 4 sources of combustion emission, crust related sources, traffic related sources and volatile species from coal combustion. The elements can be roughly divided into 3 groups by size distribution and enrichment factors method (EFs). Group 1 elements are crust related and mainly found within coarse mode including Al, Mg, Ca, Sc, Ti, Fe, Sr, Zr and Ba; Group 2 elements are fossil fuel related and mostly concentrated in accumulation mode including S, As, Se, Ag, Cd, Tl and Pb; Group 3 elements are multi-source related and show multi-mode distribution including Be, Na, K, Cr, Mn, Co, Ni, Cu, Zn, Ga, Mo, Sn and Sb. The EFs of Be, S, Cr, Co, Ni, Cu, Ga, Se, Mo, Ag, Cd, Sb, Tl and Pb show higher values in winter than in summer indicating sources of coal combustion for heating in winter. The abundance of Cu and Sb in coarse mode is about 2-6 times higher at curbside site than at urban site indicating their traffic sources. Coal burning may be the major source of Pb in Beijing since the phase out of leaded gasoline, as the EFs of Pb are comparable at both urban and curbside sites, and about two times higher in winter than that in summer.

Dephosphorylated Polymerase I and Transcript Release Factor Prevents Allergic Asthma Exacerbations by Limiting IL-33 Release.

BACKGROUND: Asthma is a chronic inflammatory disease characterized by airway inflammation and airway hyperresponsiveness (AHR). IL-33 is considered as one of the most critical molecules in asthma pathogenesis. IL-33 is stored in nucleus and passively released during necrosis. But little is known about whether living cells can release IL-33 and how this process is regulated. OBJECTIVE: We sought to investigate the role of polymerase I and transcript release factor (PTRF) in IL-33 release and asthma pathogenesis. METHODS: Ovalbumin (OVA)-induced asthma model in PTRF+/- mice were employed to dissect the role of PTRF in vivo. Then, further in vitro experiments were carried out to unwind the potential mechanism involved. RESULTS: In OVA asthma model with challenge phase, PTRF+/- mice showed a greater airway hyper-reaction, with an intense airway inflammation and more eosinophils in bronchoalveolar lavage fluid (BALF). Consistently, more acute type 2 immune response in lung and a higher IL-33 level in BALF were found in PTRF+/- mice. In OVA asthma model without challenge phase, airway inflammation and local type 2 immune responses were comparable between control mice and PTRF+/- mice. Knockdown of PTRF in 16HBE led to a significantly increased level of IL-33 in cell culture supernatants in response to LPS or HDM. Immunoprecipitation assay clarified Y158 as the major phosphorylation site of PTRF, which was also critical for the interaction of IL-33 and PTRF. Overexpression of dephosphorylated mutant Y158F of PTRF sequestered IL-33 in nucleus together with PTRF and limited IL-33 extracellular secretion. CONCLUSION: Partial loss of PTRF led to a greater AHR and potent type 2 immune responses during challenge phase of asthma model, without influencing the sensitization phase. PTRF phosphorylation status determined subcellular location of PTRF and, therefore, regulated IL-33 release.

The natural compound nujiangexanthone A suppresses mast cell activation and allergic asthma.

Mast cells play an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. The genus Garcinia of the family Guttiferae is well known as a prolific source of polycyclic polyprenylated acylphloroglucinols and bioactive prenylated xanthones, which exhibit various biological activities including antibacterial, antifungal, anti-inflammatory, antioxidant, and cytotoxic effects. Nujiangexanthone A (N7) is a novel compound isolated from the leaves of Garcinia nujiangensis. In this paper, we sought to determine the anti-allergic and anti-inflammation activity of N7 in vivo and its mechanism in vitro. We found N7 suppressed IgE/Ag induced mast cell activiation, including degranulation and production of cytokines and eicosanoids, through inhibiting Src kinase activity and Syk dependent pathways. N7 inhibited histamine release, prostaglandin D2 and leukotriene C4 generation in mast cell dependent passive cutaneous anaphylaxis animal model. We also found N7 inhibited the IL-4, IL-5, IL-13 and IgE levels in ovalbumin-induced asthma model. Histological studies demonstrated that N7 substantially inhibited OVA-induced cellular infiltration and increased mucus production in the lung tissue. Our study reveals the anti-allergic function of N7, thereby suggesting the utility of this compound as a possible novel agent for preventing mast cell-related immediate and delayed allergic diseases.

Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systemic review and meta-analysis.

BACKGROUND: In the 2014 Global initiative for chronic Obstructive Lung Disease guidelines, bronchiectasis was for the first time defined as a comorbidity of chronic obstructive pulmonary disease (COPD), and this change has been retained in the 2015 update, which emphasizes the influence of bronchiectasis in the natural history of COPD. The present meta-analysis was aimed at summarizing the impact of bronchiectasis on patients with COPD. METHODS: Databases including Embase, PubMed, and the Cochrane Central Register of Controlled Trials were searched comprehensively to identify all relevant human clinical studies published until August 2014. Bronchiectasis was confirmed either by computed tomography or high-resolution computed tomography. One or more clinicopathological or demographical characteristics, including age, sex, smoking history, daily sputum production, exacerbations, inflammatory biomarkers, lung function, and colonization by potentially pathogenic microorganisms (PPMs), were compared between COPD patients with and without bronchiectasis. RESULTS: Six observational studies with 881 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with COPD was 54.3%, ranging from 25.6% to 69%. Coexistence of bronchiectasis and COPD occurred more often in male patients with longer smoking history. Patients with COPD and comorbid bronchiectasis had greater daily sputum production, more frequent exacerbation, poorer lung function, higher level of inflammatory biomarkers, more chronic colonization by PPMs, and higher rate of Pseudomonas aeruginosa isolation. CONCLUSION: In spite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of bronchiectasis in patients with COPD in all directions, indicating that coexistence of bronchiectasis should be considered a pathological phenotype of COPD, which may have a predictive value.

USP17-mediated deubiquitination and stabilization of HDAC2 in cigarette smoke extract-induced inflammation.

Histone deacetylase HDAC2 regulates genes transcription via removing the acetyl group from histones. Glucocorticoids, the most potent anti-inflammatory treatment available for inflammatory diseases, inhibit the expression of inflammatory genes by recruiting HDAC2 to activated genes. In the lungs of patients who smoke and have chronic obstructive pulmonary disease (COPD) or asthma, glucocorticoids are not effective enough to suppress airway inflammation, which is so called "glucocorticoid resistance", due to decreased HDAC2 level caused by cigarette smoke. We report that the ubiquitin-specific protease USP17 interacts with HDAC2. USP17 deubiquitinates and stabilizes the protein level of HDAC2. In cigarette smoke extract-exposed airway epithelial cells and macrophages, HDAC2 is excessively ubiquitinated and degraded in the proteasome attributed to low expression of USP17. Furthermore, over-expression of USP17 blocks the destruction of HDAC2 induced by cigarette smoke extract. These results provide a new insight into the mechanisms of glucocorticoid resistance in airway inflammatory disease. Small molecules which can specifically induce the expression of USP17 might be useful in reversing glucocorticoid resistance.