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Background/aims: Obstructive sleep apnea (OSA) is prevalent in older patients with idiopathic pulmonary fibrosis (IPF); however, it is underrecognized. OSA is characterized by intermittent hypoxia (IH) and sleep fragmentation. In this study, we evaluated the effects of IH in an older mouse model of bleomycin-induced lung fibrosis., Methods: Bleomycin-induced mice (C57BL/6, female) were randomly divided into four groups of young vs. old and room air (RA)-exposed vs. IH-exposed. Mice were exposed to RA or IH (20 cycles/h, FiO2 nadir 7 ± 0.5%, 8 h/day) for four weeks. The mice were sacrificed on day 28, and blood, bronchoalveolar lavage (BAL) fluid, and lung tissue samples were obtained., Results: The bleomycin-induced IH-exposed (EBI) older group showed more severe inflammation, fibrosis, and oxidative stress than the other groups. The levels of inflammatory cytokines in the serum and BAL fluid increased in the EBI group. Hydroxyproline levels in the lung tissue increased markedly in the EBI group., Conclusion: This study demonstrates the possible harmful impact of OSA in an elderly mouse model of lung fibrosis. This study further suggests that older patients with IPF and OSA may be more of a concern than younger patients with IPF. Further research is required in this area.

Background/aims: We explored the effects of intermittent normobaric hyperoxia alone or combined with chemotherapy on the growth, general morphology, oxidative stress, and apoptosis of benzo[a]pyrene (B[a]P)-induced lung tumors in mice., Methods: Female A/J mice were given a single dose of B[a]P and randomized into four groups: control, carboplatin (50 mg/kg intraperitoneally), hyperoxia (95% fraction of inspired oxygen), and carboplatin and hyperoxia. Normobaric hyperoxia (95%) was applied for 3 hours each day from weeks 21 to 28. Tumor load was determined as the average total tumor numbers and volumes. Several markers of oxidative stress and apoptosis were evaluated., Results: Intermittent normobaric hyperoxia combined with chemotherapy reduced the tumor number by 59% and the load by 72% compared with the control B[a]P group. Intermittent normobaric hyperoxia, either alone or combined with chemotherapy, decreased the levels of superoxide dismutase and glutathione and increased the levels of catalase and 8-hydroxydeoxyguanosine. The Bax/Bcl-2 mRNA ratio, caspase 3 level, and number of transferase-mediated dUTP nick end-labeling positive cells increased following treatment with hyperoxia with or without chemotherapy., Conclusions: Intermittent normobaric hyperoxia was found to be tumoricidal and thus may serve as an adjuvant therapy for lung cancer. Oxidative stress and its effects on DNA are increased following exposure to hyperoxia and even more with chemotherapy, and this may lead to apoptosis of lung tumors.

A hypoxic microenvironment leads to cancer progression and increases the metastatic potential of cancer cells within tumors via epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. The hypoxic response pathway can occur under oxygen tensions of < 40 mmHg through hypoxia-inducible factors (HIFs), which are considered key mediators in the adaptation to hypoxia. Previous studies have shown that cellular responses to hypoxia are required for EMT and cancer stemness maintenance through HIF-1α and HIF-2α. The principal transcription factors of EMT include Twist, Snail, Slug, Sip1 (Smad interacting protein 1), and ZEB1 (zinc finger E-box-binding homeobox 1). HIFs bind to hypoxia response elements within the promoter region of these genes and also target cancer stem cell-associated genes and mediate transcriptional responses to hypoxia during stem cell differentiation. Acquisition of stemness characteristics in epithelial cells can be induced by activation of the EMT process. The mechanism of these phenotypic changes includes epigenetic alterations, such as DNA methylation, histone modification, chromatin remodeling, and microRNAs. Increased expression of EMT and pluripotent genes also play a role through demethylation of their promoters. In this review, we summarize the role of hypoxia on the acquisition of EMT and cancer stemness and the possible association with epigenetic regulation, as well as their therapeutic applications.

Background/aims: An association between reduced pulmonary function and diabetes has been observed. Our aim was to evaluate the prevalence and risk factors associated with reduced pulmonary function in diabetic patients., Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey 2011 to 2013. The study population included data from 8,784 participants (including 1,431 diabetics) aged ≥ 40 years. Reduced pulmonary function was defined as patients with restrictive (forced expiratory volume in 1 second/forced vital capacity [FEV 1 /FVC] ≥ 0.7 and FVC < 80% of predicted value) or obstructive (FEV 1 /FVC < 0.7) patterns., Results: Subjects with diabetes had a higher prevalence of restrictive (18.4% vs. 9.4%, p < 0.001) and obstructive impairments (20% vs. 12.6%, p < 0.001) than those without diabetes. The adjusted odds ratios (aORs) (95% confidence interval [CI]) for obstructive and restrictive pulmonary impairment were 0.91 (0.75 to 1.11) and 1.57 (1.30 to 1.89), respectively. In the diabetes population, age (aOR, 1.04; 95% CI, 1.02 to 1.06), male sex (aOR, 1.40; 95% CI, 1.04 to 1.88), and body mass index (aOR, 1.15; 95% CI, 1.10 to 1.21) were independently associated with restrictive pulmonary impairment. Age (aOR, 1.12; 95% CI, 1.09 to 1.14), male sex (aOR, 4.24; 95% CI, 2.42 to 7.44), and smoking at any point (ever-smoker: aOR, 1.96; 95% CI, 1.16 to 3.33) were independent risk factors for obstructive pulmonary impairment in diabetics. Diabetes duration or glycated hemoglobin had no association with pulmonary impairment in diabetes., Conclusions: Subjects with diabetes had a higher risk of restrictive pulmonary impairment than those without diabetes after adjusting for confounding factors. Older age, male sex, body mass index, and smoking were associated with reduced lung function in diabetes.

Background/aims: The pulmonary abnormalities (principally restrictive abnormalities) are characteristic of renal transplant recipients or those with end-stage renal disease. Our aim was to explore whether the prevalence of spirometric abnormalities was influenced by the estimated glomerular filtration rates (GFRs) in a Korean general population., Methods: We used data obtained during the 2010 to 2012 Korean National Health and Nutrition Examination Survey, a national cross-sectional survey. We analyzed data from subjects for whom spirometric assays and estimated GFRs were of acceptable quality., Results: A total of 8,809 subjects (3,868 male and 4,941 female) was included. In both males and females with GFR values < 60 mL/min/1.73 m 2 , the linear trends toward the presence of obstructive and restrictive patterns were significant. However, the percent predicted forced vital capacity (FVC) decreased with a decline in the estimated GFR, but only in males ( p for trend < 0.0031). Multivariate linear regression analysis showed a decline in the estimated GFR was independently associated with falls in the percent predicted FVC and the forced expiratory volume in 1 second/FVC ratio in both males and females. However, the percent predicted FVC was independently predictive only in males ( p = 0.002)., Conclusions: Impaired pulmonary function was associated with a decline in the estimated GFR. The percent predicted FVC decrease paralleled the decline in estimated GFR in male only. Careful interpretation of pulmonary function test data is required in patients with decreased GFRs or impaired renal function, especially males., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background/aims: This study examined prevalence and risk factors of periodontitis in representative samples of Korean adults, with and without diabetes mellitus (DM)., Methods: Data from the 2012 Korean National Health and Nutritional Examination Survey were analyzed. A total of 4,477 adults (≥ 30 years old) were selected from 8,057 individuals who completed a nutrition survey, a self-reported general health behavior questionnaire, an oral examination, an oral hygiene behaviors survey, and laboratory tests. DM was defined as a fasting plasma glucose ≥ 126 mg/dL, or self-reported diagnosed diabetes, or current use of oral hypoglycemic agents and/or insulin. The community periodontal index was used to assess periodontitis status and comparisons between the periodontitis and the non-periodontitis group, were performed, according to the presence of DM. Risk factors for periodontitis in adults with DM and without DM were evaluated by multiple logistic regression analysis., Results: The prevalence of periodontitis was significantly higher in adults with DM (43.7%) than in those without DM (25%, p < 0.001). In adults without DM, risk factors for periodontitis were older age, male, urban habitation, waist circumference, smoking, oral pain, and less frequent tooth brushing. Significant risk factors for periodontitis in adults with DM were the smoking, oral pain, and not-using an oral hygiene product., Conclusions: Adults with DM have an increased risk of periodontitis than those without DM. Current smoking and oral pain increase this risk. Using an oral hygiene product can reduce risk of periodontal disease in adults with DM., Competing Interests: No potential conflict of interest relevant to this article was reported.

Kawasaki Disease (KD) is an acute, febrile, multisystem disease of children. More severe complications in 15-25% of cases include, the development of coronary aneurysms, ischemic heart disease, and sudden cardiac death. The standard treatment for significant coronary artery stenosis has generally been aortocoronary bypass surgery, although percutaneous transluminal coronary angioplasty (PTCA) has been described in a small number of patients. This report describes a 14 year old boy with a history of KD who developed multiple coronary aneurysms and stenosis. We performed PTCA, which was successful in relieving the stenosis of the left circumflex artery.