Browsing by Subject "Pulmonary fibrosis"

Now showing 1 - 3 of 3
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    Are pulmonary fibrosis and Alzheimer's disease linked? Shared dysregulation of two miRNA species and downstream pathways accompany both disorders
    (American Society for Biochemistry and Molecular Biology, 2017-12-08) Lahiri, Debomoy K.; Maloney, Bryan; Greig, Nigel H.; Psychiatry, School of Medicine
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    MMP-3 mediates copper oxide nanoparticle-induced pulmonary inflammation and fibrosis
    (Springer Nature, 2024-07-19) Zhang, Yuanbao; Zhang, Zhenyu; Mo, Yiqun; Zhang, Yue; Yuan, Jiali; Zhang, Qunwei; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: The increasing production and usage of copper oxide nanoparticles (Nano-CuO) raise human health concerns. Previous studies have demonstrated that exposure to Nano-CuO could induce lung inflammation, injury, and fibrosis. However, the potential underlying mechanisms are still unclear. Here, we proposed that matrix metalloproteinase-3 (MMP-3) might play an important role in Nano-CuO-induced lung inflammation, injury, and fibrosis. Results: Exposure of mice to Nano-CuO caused acute lung inflammation and injury in a dose-dependent manner, which was reflected by increased total cell number, neutrophil count, macrophage count, lactate dehydrogenase (LDH) activity, and CXCL1/KC level in bronchoalveolar lavage fluid (BALF) obtained on day 3 post-exposure. The time-response study showed that Nano-CuO-induced acute lung inflammation and injury appeared as early as day 1 after exposure, peaked on day 3, and ameliorated over time. However, even on day 42 post-exposure, the LDH activity and macrophage count were still higher than those in the control group, suggesting that Nano-CuO caused chronic lung inflammation. The Nano-CuO-induced pulmonary inflammation was further confirmed by H&E staining of lung sections. Trichrome staining showed that Nano-CuO exposure caused pulmonary fibrosis from day 14 to day 42 post-exposure with an increasing tendency over time. Increased hydroxyproline content and expression levels of fibrosis-associated proteins in mouse lungs were also observed. In addition, Nano-CuO exposure induced MMP-3 overexpression and increased MMP-3 secretion in mouse lungs. Knocking down MMP-3 in mouse lungs significantly attenuated Nano-CuO-induced acute and chronic lung inflammation and fibrosis. Moreover, Nano-CuO exposure caused sustained production of cleaved osteopontin (OPN) in mouse lungs, which was also significantly decreased by knocking down MMP-3. Conclusions: Our results demonstrated that short-term Nano-CuO exposure caused acute lung inflammation and injury, while long-term exposure induced chronic pulmonary inflammation and fibrosis. Knocking down MMP-3 significantly ameliorated Nano-CuO-induced pulmonary inflammation, injury, and fibrosis, and also attenuated Nano-CuO-induced cleaved OPN level. Our study suggests that MMP-3 may play important roles in Nano-CuO-induced pulmonary inflammation and fibrosis via cleavage of OPN and may provide a further understanding of the mechanisms underlying Nano-CuO-induced pulmonary toxicity.
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    Six-Minute Walk Test as a Predictive Measure of Exercise Capacity in Adults with Type 2 Diabetes
    (Wolters Kluwer, 2018-07) Nolen-Doerr, Eric; Crick, Kent; Saha, Chandan; de Groot, Mary; Pillay, Yegan; Shubrook, Jay H.; Donley, David; Hornsby, W. Guyton; Biostatistics, School of Public Health
    Objective: The 6 Minute Walk Test (6MWT) is a measure that is routinely used to assess a response to treatment for cardiopulmonary diseases such as pulmonary fibrosis and congestive heart failure. The measure has never been verified as a valid measure of exercise capacity in the highly prevalent patient population of type 2 diabetes (T2DM). This study investigated the correlation between the 6MWT and graded exercise testing (GXT) in an effort to validate the 6MWT as a quality tool for assessing exercise capacity in adults with T2DM. Research Design and Method: This is a secondary data analysis of Program ACTIVE II, a randomized controlled trial designed to assess the effectiveness of two behavioral interventions on depression and glycemic outcomes in adults with T2DM. The correlation of 6MWT and predicted VO2 max (PVO2M) using GXT was examined in a subsample of participants at the time of study enrollment and at post-intervention. Results: PVO2M showed a significant correlation with 6MWT distance both at baseline (r=0.57, p=0.014) and post-intervention (r = 0.66, p = 0.037). The regression analysis of baseline data revealed that 6MWT distance alone explained 45% (F = 13.03, p = .0024) of the variability in PVO2M. When combined with the SF-12 physical health component score (PCS), 6MWT explained 66% (F = 13.62, p < .001) of the variance in PVO2M. After adjusting for PCS, 6MWT distance explained an additional 30% variability in PVO2M. Conclusions: Findings from this study indicate that the 6MWT and predicted exercise capacity are significantly correlated. The 6MWT can be used to estimate exercise capacity in adults with T2DM.