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BACKGROUND: Airway remodeling is an important pathological of airflow limitation in chronic obstructive pulmonary disease (COPD).However,its mechanism still needs to be further clarify. METHODS: Animals:Healthy male C57BL/6 mice aged 4-6 weeks were randomly divided into control group and cigarette smoke(CS)group. Mice in the CS group were placed in a homemade glass fumigator, 5 cigarettes/time, 40 min/time, 4 times/day, 5 days/week, for 24 weeks. Mice in the control group were placed in a normal air environment.Cells:BEAS-2B cells were stimulated with 0.1%cigarette smoke extract(CSE).HE staining, immunohistochemical staining and Masson staining were used to observe the pathological of lung tissues, transmission electron microscopy was used to observe the structural of mitochondria in bronchial epithelial cells.Western blotting was used to detect the expression of STAT3,transforming growth factor-ß1(TGF-ß1),microtubule-associated protein 1A/1B-light chain3(LC3),PINK1,Parkin,E-cadherin,zonula occludens1(ZO-1),vimentin and snail family transcriptional inhibitor1 (Snail1),and MitoSOX Red was used to detect mitochondrial reactive oxygen species(mtROS). RESULTS: CS exposure causes lung parenchymal destruction and airway remodeling in mice.Compared to the control group,the expression of p-STAT3,TGF-ß1 and EMT in the whole lung homogenate of the CS group was increased.Mitochondrial architecture disruption in bronchial epithelial cells of CS mice, with impaired PINK1-Parkin-dependent mitophagy.In vitro experiments showed that CSE exposure led to STAT3 activation, increased TGF-ß1,EMT and enhanced PINK1-Parkin-mediated mitophagy.STAT3 inhibition reversed TGF-ß1 upregulation induced by CSE and improved CSE-induced EMT and mitophagy.Inhibition of mitophagy improves EMT induced by CSE. Inhibition of mitophagy reduces STAT3-induced EMT. CONCLUSION: CS activates the STAT3,and activated STAT3 promotes EMT in bronchial epithelial cells by enhancing PINK1-Parkin-mediated mitophagy and TGF-ß1 signaling.Moreover, activated STAT3 can promote EMT directly.This may be one of the mechanisms by which CS causes small airway remodeling in COPD.
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Background: Chronic obstructive pulmonary disease (COPD) is significantly influenced by oxidative stress. Recent studies have elucidated the anti-oxidative stress properties of peroxisome proliferator-activated receptors γ (PPARγ), augmenting its known anti-inflammatory effects. The exact influence of PPARγ on oxidative stress in COPD remains elusive. This study aimed to investigate the potential mechanism by which PPARγ counteracts the oxidative stress instigated by cigarette smoke in macrophages. Methods: Macrophages were cultured and exposed to 1% cigarette smoke extract (CSE), 1 µg/mL erythromycin (EM), and 10 µmol/mL GW9662 (a PPARγ antagonist). Reactive oxygen species (ROS) in macrophages was identified using fluorescent microscopy. PPARγ expression was ascertained through reverse transcription-polymerase chain reaction (RT-PCR) and Western blot techniques. The superoxide dismutase (SOD) in macrophage supernatant was measured by enzyme linked immunosorbent assay (ELISA), as was malondialdehyde (MDA). Results: Our results shown that cigarette smoke stimulated macrophages to increase ROS release, decrease the expression of PPARγ, increase the expression of MDA and decrease the expression of SOD. After PPARγ inhibitor acted on macrophages stimulated by cigarette smoke, the expression of MDA was inhibited and the content of SOD increased. When EM was used to treat macrophages stimulated by cigarette smoke, the expression of ROS decreased, the expression of PPARγ increased, the expression of MDA decreased and the expression of SOD increased. Conclusions: This study suggests that PPARγ plays an anti-oxidative role by inhibiting the expression of MDA and promoting the expression of SOD. Cigarette smoke induces oxidative stress by inhibiting PPARγ pathway. EM inhibits oxidative stress by activating PPARγ pathway.
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Cytomegalovirus (CMV) infection is one of the most common infectious complications following hematopoietic stem cell transplantation (HSCT); however, cases involving multiple organs at the same time are rare. The present study describes a case of CMV pneumonia combined with CMV DNAemia and CMV cystitis after HSCT. A 33-year-old male patient with acute myeloid leukemia was treated with HSCT. The first month after HSCT, the patient developed a cough and shortness of breath. At 2 months post-HSCT, the patient developed hematuria. The CMV DNA levels in the blood and urine were elevated; bronchoalveolar lavage fluid (BALF) was also positive for CMV DNA. Heterotypic cells exhibiting a large nuclear morphology were observed in the BALF and bronchial brushes. Recurrent and progressive ground-glass opacities were evident on chest computed tomography. The patient was diagnosed with CMV pneumonia complicated by CMV DNAemia and CMV cystitis, and was treated with a combination of ganciclovir and foscarnet, along with immunoglobulin therapy. The patient was cured and discharged. It was determined that the CMV DNA in the blood was inconsistent with that in the BALF, which delayed the early diagnosis of CMV pneumonia. The association between T-cell immune function and the therapeutic efficacy for CMV multi-organ infection following HSCT is known to be significant. Moreover, the timely administration of ganciclovir and foscarnet in combination with immunoglobulin therapy demonstrated favorable clinical outcomes.