High mobility group protein B1 (HMGB1) has been implicated as an important mediator in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). However, the expression of HMGB1 in plasma and sputum of patients with asthma and COPD across disease severity needs to be defined. The objective of the study was to examine the induced sputum and plasma concentrations of HMGB1 in COPD and asthmatic patients to determine differences in HMGB1 levels between these diseases and their relationship with airway obstruction and inflammatory patterns. A total of 147 participants were enrolled in this study. The participants included 34 control subjects, 61 patients with persistent asthma (according to the Global Initiative for Asthma [GINA] guidelines) and 47 patients with stable COPD (stratified by Global Initiative for Chronic Obstructive Lung Disease [GOLD] status). Spirometry was performed before sputum induction. HMGB1 levels in induced sputum and plasma were determined by enzyme-linked immunosorbent assay. Sputum and plasma concentrations of HMGB1 in patients with asthma and COPD were significantly higher than concentrations in control subjects and were significantly negatively correlated with forced expiratory volume in 1 s (FEV 1 ), FEV 1 (% predicted) in all 147 participants. The levels of HMGB1 in induced sputum of COPD patients were significantly higher than those of asthma patients and healthy controls (P < 0.001). This difference was present even after adjusting for sex, age, smoking status, daily dose of inhaled corticosteroids and disease severity. There were no significant differences in HMGB1 levels between patients with eosinophilic and noneosinophilic asthma. HMGB1 levels in asthmatic and COPD patients were positively correlated with neutrophil counts and percentage of neutrophils. In multivariate analysis, the two diseases (asthma and COPD) and disease severity were independent predictors of sputum HMGB1, but not smoking, age or use of inhaled corticosteroids. In conclusion, these data support a potential role for HMGB1 as a biomarker and diagnostic tool for the differential diagnosis of asthma and COPD. The importance of this observation on asthma and COPD mechanisms and outcomes should be further investigated in large prospective studies.
SMS can improve PCA, and it has a greater advantage in improving follow-up rate and asthma-specific quality of life than traditional programs.
RNA interference (RNAi) describes the ability of double-stranded RNA (dsRNA) to inhibit homologous gene expression at the RNA level. Its specificity is sequence-based and depends on the sequence of one strand of the dsRNA corresponding to part or all of a specific gene transcript. In this study we adopted plant-mediated RNAi technology that targets Sitobion avenae (S. avenae) to enable gene silencing in the aphid and to minimize handling of the insects during experiments. S. avenae was selected for this study because it causes serious economic losses to wheat throughout the world. The carboxylesterase (CbE E4) gene in S. avenae was homologously cloned, which increased synthesis of a protein known to be critical to the resistance (tolerance) this species has developed to a wide range of pesticides. A plant RNAi vector was constructed, and transgenic Triticum aestivum (dsCbE1-5 and dsCbE2-2 lines) expressing CbE E4 dsRNA were developed. S. avenae were fed on dsCbE1-5 and dsCbE2-2 lines stably producing the CbE E4 dsRNA. CbE E4 gene expression in S. avenae was reduced by up to 30-60%. The number of aphids raised on dsCbE1-5 and dsCbE2-2 was lower than the number raised on non-transgenic plants. A solution of CbE E4 enzyme from S. avenae fed on dsCbE1-5 and dsCbE2-2 plants hydrolyzed only up to 20-30% Phoxim solution within 40 min whereas a solution of the enzyme from CbE E4 fed on control plants hydrolyzed 60% of Phoxim solution within 40 min. CbE E4 gene silencing was achieved by our wheat-mediated RNAi approach. This plant-mediated RNAi approach for addressing degradation-based pesticide resistance mechanisms in aphids and may prove useful in pest management for diverse agro-ecosystems.
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