BackgroundEvidence suggests that suppressor of cytokine signaling 1 (SOCS1) is crucial for the negative regulation of inflammation. We investigated the relationship between smoking, SOCS1, and leukotriene B4 (LTB4) in vitro and in clinical samples of COPD; besides which we detected the impact of LTB4 receptor 1 (BLT1) antagonist on inflammation.MethodsSOCS1 expression in bronchial mucosa was determined by immunohistochemistry and real-time polymerase chain reaction. We also detect SOCS1 and BLT1 expression in alveolar macrophages from bronchoalveolar lavage fluid (BALF) by real time-PCR, in addition to measuring the level of cytokines in BALF using enzyme-linked immunosorbent assay. In vitro, we investigated the expression of SOCS1 in cigarette smoke extract-induced mouse macrophage cell line RAW264.7 by real-time polymerase chain reaction and Western blot, and detected the level of cytokines in the supernatant by enzyme-linked immunosorbent assay. Then, we investigated the effects of BLT1 antagonist U-75302 on SOCS1 expression in these cells.ResultsWe obtained endobronchial biopsies (15 COPD patients and 12 non-COPD control subjects) and BALF (20 COPD patients and 20 non-COPD control subjects), and our results showed that SOCS1 expression significantly decreased in lung tissues from COPD patients. Inflammatory cytokines in BALF were higher in COPD and these inflammatory cytokines negatively correlate with SOCS1 levels. Further, the BLT1 antagonist restored SOCS1 expression and in turn inhibited inflammatory cytokine secretion in vitro.ConclusionLong-term cigarette smoke exposure induced SOCS1 degradation and LTB4 accumulation, which was associated with emphysema and inflammation. A BLT1 antagonist might be a potential therapeutic candidate for the treatment of COPD.

INTRODUCTIONChronic obstructive pulmonary disease (COPD) is characterized by persistent respiratory symptoms and concurrent progressive airflow limitation [1][2][3]. Patients may experience episodes of exacerbated respiratory symptoms, and the frequency of exacerbations requiring hospitalization increases, resulting in significant social and economic burden and one of the major causes of morbidity and mortality worldwide [4,5]. The pathogenesis of COPD and exacerbations may be associated with inflammatory cells, including macrophages, neutrophils, and T lymphocytes [6,7]. These cells are crucial in parenchymal destruction and development of airflow limitation in patients with COPD [8,9]. Chemokines and their receptors regulate leukocyte adhesion and homing, and these receptors play a critical role in trafficking of leukocytes to sites of injury and www.aging-us.com

BackgroundInflammation is an important cause of COPD. Alveolar macrophages are the major innate immune cells that have an important role in COPD pathology. Class A scavenger receptor (SR-A) is a pattern recognition receptor expressed on macrophages. This study investigates the role of SR-A in COPD progression via regulation of inflammation.Patients and methodsSR-A expression in COPD patients and control subjects (smokers and nonsmokers without COPD) was measured by immunohistochemistry, immunofluorescence, and real-time PCR. The cytokine levels in BAL were measured by enzyme-linked immunosorbent assay. To further prove our hypothesis, we treated RAW264.7 cells that overexpress SR-A with lipopolysaccharides, poly(I:C), cigarette smoke extract, and H1N1 influenza separated from patients for 24 h and examined the levels of inflammatory cytokines.ResultsIn both groups, COPD and smokers without COPD, SR-A expression level was upregulated in alveolar macrophages. SR-A mRNA level was positively correlated with inflammatory cytokines and negatively correlated with FEV1% predicted in COPD patients. In RAW-SR-A cells, level of inflammatory cytokines was significantly higher when compared with control ones.ConclusionSR-A could increase inflammation stimulated by cigarette smoke extracts, bacteria, and virus, leading to long-term inflammation in COPD, and thus might be used as a new therapeutic target for COPD treatment.

Mycobacterium tuberculosis antimicrobial resistance has been continually reported and is a major public health issue worldwide. Rapid prediction of drug resistance is important for selecting appropriate antibiotic treatments, which significantly increases cure rates. Gene sequencing technology has proven to be a powerful strategy for identifying relevant drug resistance information. This study established a sequencing method and bioinformatics pipeline for resistance gene analysis using an Oxford Nanopore Technologies sequencer. The pipeline was validated by Sanger sequencing and exhibited 100% concordance with the identified variants. Turnaround time for the nanopore sequencing workflow was approximately 12 h, facilitating drug resistance prediction several weeks earlier than that of traditional phenotype drug susceptibility testing. This study produced a customized gene panel assay for rapid bacterial identification via nanopore sequencing, which improves the timeliness of tuberculosis diagnoses and provides a reliable method that may have clinical application.

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Objectives This study aimed to investigate the involvement of MCM3AP antisense RNA 1 (MCM3AP-AS1) in chronic obstructive pulmonary disease (COPD). Methods The expression levels of plasma MCM3AP-AS1 in COPD patients and healthy controls were measured by quantitative PCR before treatment and at 3 months after the initiation of treatment (post-treatment) from COPD patients. The role of MCM3AP-AS1 in regulating the proliferation of human bronchial smooth muscle cells (HBSMCs) was explored by a cell proliferation assay. Results We found that MCM3AP-AS1 expression was downregulated in the plasma of COPD patients compared with controls. Among controls, MCM3AP-AS1 expression was lower in smokers than never-smokers. A 3-year follow-up study showed that, among smokers, patients with low MCM3AP-AS1 expression showed a higher incidence of COPD. After treatment for COPD, MCM3AP-AS1 expression significantly increased. The cell proliferation assay showed that MCM3AP-AS1 overexpression decreased the proliferation rate of HBSMCs. MCM3AP-AS1 silencing had the opposite effect. Conclusions MCM3AP-AS1 appears to be downregulated in COPD and to predict its occurrence. MCM3AP-AS1 regulates the proliferation of HBSMCs to participate in airway remodeling.