The DNA repair enzyme 8‐oxoguanine DNA glycosylase‐1 (OGG1) is involved in early embryonic development, as well as in multiple conditions, including cardiac fibrosis, diabetes, and neurodegenerative diseases. But, function of OGG1 in pulmonary fibrosis was not entirely clear. In this study, we identified a novel function of OGG1 in the cell transformation process in pulmonary fibrosis. We demonstrated that OGG1 and Smad7 co‐localize and interact in A549 cells. Bleomycin‐induced pulmonary fibrosis was established in wild‐type (WT) and Ogg1‐/‐ mice. Upon treatment with transforming growth factor (TGF)‐β1, increased OGG1 expression was observed in WT mice with pulmonary fibrosis as well as in A549 cells, MRC‐5 cells, and primary rat type II alveolar epithelial cells. The increased expression of OGG1 promoted cell migration, while OGG1 depletion decreased migration ability. Expression of the transformation‐associated markers vimentin and alpha‐smooth muscle actin were also affected by OGG1. We also observed that OGG1 promoted TGF‐β1‐induced cell transformation and activated Smad2/3 by interacting with Smad7. The interaction between OGG1 and the TGF‐β/Smad axis modulates the cell transformation process in lung epithelial cells and fibroblasts. Moreover, we demonstrated that Ogg1 deficiency relieved pulmonary fibrosis in bleomycin‐treated mice. Ogg1 knockout decreased the bleomycin‐induced expression of Smad7 and phosphorylation of Smad2/3 in mice. These findings suggest that OGG1 has multiple biological functions in the pathogenesis of pulmonary fibrosis.
To evaluate the association between severe pulmonary embolism events and bevacizumab, we conducted the first meta-analysis evaluating the incidence and risk of pulmonary embolism associated with bevacizumab-based therapy. We searched PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov up to September 2016 for randomized controlled trials comparing bevacizumab with no bevacizumab on cancer patients. Incidence rates, relative risks, and 95% confidence intervals were calculated using fixed- or random-effects models. The primary end point was the association of bevacizumab with pulmonary embolism. Subgroup analyses were performed according to tumor type, dose, and publication status. In total, 23 randomized controlled trials were included. For patients receiving bevacizumab, the overall incidence of severe pulmonary embolism events was 1.76% (95% confidence interval = 1.25%-2.27%). Cancer patients treated with bevacizumab did not increase the risk of pulmonary embolism events (relative risk = 1.00, 95% confidence interval = 0.80-1.25). No significant differences in pulmonary embolism incidence or risk among subgroup analyses were observed. No evidence of publication bias was observed. This study suggested that bevacizumab may not increase the risk of pulmonary embolism in cancer patients.
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