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Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis

Zhao et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752
Sep 2023  
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In Silico study identifying IGF1 as a shared gene between pulmonary fibrosis and hypertension that promotes inflammation, fibrosis, and cell proliferation when overactivated. Molecular docking analysis demonstrated ivermectin directly binds IGF1 through multiple binding modes. This suggests ivermectin may inhibit IGF1 signaling. Since uncontrolled inflammation and lung fibrosis are major issues in severe COVID-19, ivermectin's ability to bind IGF1 indicates it may be able to reduce IGF1-mediated inflammation and fibrosis. By binding and inhibiting IGF1, ivermectin could potentially attenuate damaging effects of hyperactive IGF1 signaling on lung tissues observed in critical COVID-19 cases. This proposed mechanism of action via IGF1 binding provides a rationale for how ivermectin could protect lungs against inflammatory damage in severe COVID-19.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CLpro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacterium which plays a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Zhao et al., 4 Sep 2023, peer-reviewed, 12 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
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Identification of the shared gene signatures between pulmonary fibrosis and pulmonary hypertension using bioinformatics analysis
Hui Zhao, Lan Wang, Yi Yan, Qin-Hua Zhao, Jing He, Rong Jiang, Ci-Jun Luo, Hong-Ling Qiu, Yu-Qing Miao, Su-Gang Gong, Ping Yuan, Wen-Hui Wu
Frontiers in Immunology, doi:10.3389/fimmu.2023.1197752
Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are
Ethics statement The studies involving humans were approved by the Ethics Committee of Shanghai Pulmonary Hospital (numbers: K22-137Y). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. Author contributions HZ, LW, and YY investigated the literature research, got the data, and analyzed the data. Q-HZ and JH wrote the article. RJ and C-JL modified the figures. H-LQ and Y-QM revised the article. W-HW, PY, and S-GG conceived the idea of the study, designed the steps of the study, and directed the data analysis. All authors contributed to the article and approved the submitted version. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Supplementary material The Supplementary Material for this article can be found online at: full#supplementary-material
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