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1دورية أكاديمية
المؤلفون: Mohamed El-Agamy Farh, Hyun-Jin Kim, Sang-Yeon Kim, Jae-Hee Lee, Hajeong Lee, Ronglan Cui, Soorim Han, Dong Wook Kim, Sunjoo Park, Yoon-Jin Lee, Yun-Sil Lee, Insuk Sohn, Jaeho Cho
المصدر: International Journal of Molecular Sciences, Vol 25, Iss 7, p 3766 (2024)
مصطلحات موضوعية: radiation-induced lung injury, stereotactic body radiation therapy, 65 Gy and 75 Gy, inflammation and fibrosis stages, micro-computed tomography, histopathological analysis, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.
وصف الملف: electronic resource
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2دورية أكاديمية
المؤلفون: Sang Yeon Kim, Sunjoo Park, Ronglan Cui, Hajeong Lee, Hojung Choi, Mohamed El-Agamy Farh, Hai In Jo, Jae Hee Lee, Hyo Jeong Song, Yoon-Jin Lee, Yun-Sil Lee, Bong Yong Lee, Jaeho Cho
المصدر: International Journal of Molecular Sciences, Vol 24, Iss 22, p 16265 (2023)
مصطلحات موضوعية: radiation-induced lung fibrosis, irradiation, NXC736, NLRP3, Biology (General), QH301-705.5, Chemistry, QD1-999
الوصف: Radiation-induced lung fibrosis (RILF) is a common complication of radiotherapy in lung cancer. However, to date no effective treatment has been developed for this condition. NXC736 is a novel small-molecule compound that inhibits NLRP3, but its effect on RILF is unknown. NLRP3 activation is an important trigger for the development of RILF. Thus, we aimed to evaluate the therapeutic effect of NXC736 on lung fibrosis inhibition using a RILF animal model and to elucidate its molecular signaling pathway. The left lungs of mice were irradiated with a single dose of 75 Gy. We observed that NXC736 treatment inhibited collagen deposition and inflammatory cell infiltration in irradiated mouse lung tissues. The damaged lung volume, evaluated by magnetic resonance imaging, was lower in NXC736-treated mice than in irradiated mice. NXC736-treated mice exhibited significant changes in lung function parameters. NXC736 inhibited inflammasome activation by interfering with the NLRP3-ASC-cleaved caspase-1 interaction, thereby reducing the expression of IL-1β and blocking the fibrotic pathway. In addition, NXC736 treatment reduced the expression of epithelial–mesenchymal transition markers such as α-SMA, vimentin, and twist by blocking the Smad 2,3,4 signaling pathway. These data suggested that NXC736 is a potent therapeutic agent against RILF.
وصف الملف: electronic resource