2-Deoxy-D-glucose ameliorates inflammation and fibrosis in a silicosis mouse model by inhibiting hypoxia-inducible factor-1α in alveolar macrophages.

Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1ß (IL-1ß) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1ß, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.

Emerging trends in silicosis research: a scientometric review.

Silicosis is a global disease whose prevention efforts cannot be ignored today. Although numerous silicosis-related data have been published recently, emphasizing the characteristics and nature of silicosis, a summary of the developmental laws of research is lacking, especially in the visual analysis of the literature. We aim to address this issue through a scientometric review. The Web of Science Core Collection and the All Databases were searched with "silicosis" as the topic, excluding unrelated publications, and obtained data from 9802 and 1613 publications, respectively. The data was then analyzed using the Web of Science's online scientometric analysis function and CiteSpace's visual analysis functionality, including publication volume analysis, co-occurrence analysis, co-citation analysis, cluster analysis, and explosive detection. The results identify the "respiratory system" as the most influential area over a century. Furthermore, the publication's number was correlated with the gross domestic product. We ranked countries and institutions based on the frequency of publications and discovered that Europe, the USA, and China are the leading regions for silicosis research, with the USA and Europe having a stronger influence. Many reports related to artificial stone and denim jean production have been studied through citation analysis, indicating new epidemic trends in silicosis. Besides, silicosis-related diseases and the pathogenesis of silicosis were the research hotspots of silicosis through co-occurrence keyword analysis and outbreak detection. Furthermore, related diseases include coal workers' pneumoconiosis and tuberculosis, while the mechanism of silicosis includes studies on inflammation and fibrosis, oxidative stress, alveolar macrophages, apoptosis, and pathways.