ABSTRACT
Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.
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Objective To explore the clinical features of chronic granulomatous diseases and Mcleod syndrome caused by continuous X chromosome deletion. Methods The clinical data of two children diagnosed as chronic granulomatous disease and Mcleod syndrome by gene detection were retrospectively analyzed. Results Two males, 4 year 1 month and 1 year 9 month old, were both hospitalized due to persistent pulmonary infections. Both of them had a history of repeated severe infections and BCG vaccine associated lymphadenitis, and were diagnosed as X-linked chronic granulomatous disease for respiratory burst defects and deletion of all CYBB exons. Both of them had retarded motor development, and were diagnosed as DMD for detection of DMD gene exons and muscle speciifc promoter region and exon 1-2 deletion by MLPA. One case was found with obvious echinocytes, the other case showed whole exons deletion of XK gene. Both of them were diagnosed as Mcleod syndrome. Conclusion Continuous X chromosome deletion could lead to combination of Mcleod syndrome, DMD, and X-CGD, which may complicate the condition. Due to the lack of Kx antigen, repeated common blood transfusion can produce relative antibody, which lead to severe hemolytic crisis.
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Background and purpose:There are emerging evidences show that cytokines can mediate the expression and function of chemokines. CXC chemokine ligand 17 (CXCL17) is the latest member in CXC chemokine superfamily, which was identiifed in 2006. It may be involved in anti-tumor immune response. As a mucosal chemokine, CXCL17 was also proved to have anti-inlfammatory and anti-microbial effects. The purpose of this study was to ifgure out which cytokine can impact the expression of CXCL17. Methods:Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of CXCL17 in MCF-10A after cytokines stimulation, such as TNF-α, IL-1β, IFN-γand lipopolysaccharide (LPS). Western blot was used to detect the activation of the JAK-STAT pathway in MCF-10A after IFN-γinduction. Results:All tested cytokines can induce CXCL17 gene expression to varying degrees. However, the effect of IFN-γwas much more powerful by contrast with others. It can enhance the CXCL17 gene expression by about 100-fold. Western blot indicated that IFN-γcan stimulate the expression and phosphorylation of STAT1 in JAK-STAT pathway. Conclusion:Several cytokines can induce the expression of CXCL17 by breast epithelial cells, while IFN-γdramatically increased the expression of it via a JAK-STAT1-dependent pathway. CXCL17 may be the target gene of IFN-γ.
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Objective To evaluate the application of multiple locus variable number tandem repeat analysis (MLVA, 15-locus set)for genotyping of Mycobacterium tuberculosis (MTB) strains of Beijing genotype. Methods Total 72 Beijing genotype MTB strains obtained from Beijing Thoracic Hospital were genotyped by MLVA (15-locus set). The results were compared with that generated from "gold standard"IS6110-RFLP. Results After genotyped by MLVA ( 15-locus set), 72 strains were grouped into 59 types,of which 53 were unique types. The Hunter-Gaston index (HGI) of MLVA ( 15-locus set) was 0.990. The loci QUB-11b, Mtub 21 and QUB-26 were polymorphic in selected Beijing genotype strains. Genotyping by IS6110-RFLP generated 69 types, of which 66 were unique types. The HGI of IS6110-RFLP was up to 0.999, and the MLVA (15-locus set) clustered strains could be further subdivided. Conclusion MLVA(15-locus set) showed better discriminatory ability in Beijing genotype MTB strains, though secondary typing of clustered strains by IS6110-RFLP is needed.