Fig 1: An analysis of effects of high-mobility group box (HMGB)-1 neutralization on alveolar tissue injury in a mouse model of severe COVID-19(A-G) White blood cell count, (B) total protein, (C) soluble receptors for advanced glycation end products (sRAGE), (D) angiopoietin (ANG)-2, (E) total CK18, (F) CK18-M30 levels, and (G) the ratio of CK18-M30/total CK18in BALF from the mouse model of severe COVID-19 treated with an anti-HMGB-1 neutralizing antibody or an isotype control antibody are shown. Values are presented as means ± SE. *p < 0.05, **p < 0.01, ***p < 0.0001.
Fig 2: Mechanisms of alveolar epithelial cell death in a COVID-19 mouse model(A and B) Levels of (A) CK18-M30 and (B) total CK18 in bronchoalveolar lavage fluid (BALF) from a COVID-19 mouse model are shown.(C) The ratio of CK18-M30/total CK18, an indicator of the fraction of apoptosis versus total epithelial cell death, is shown.(D) HMGB-1 levels in BALF from a COVID-19 mouse model.(E and F) Images and (F) densitometry of mixed lineage kinase domain-like (MLKL), p-MLKL, gasdermin D (GSDMD), and cleaved GSDMD immunoblots of the protein extracted from the lung of a COVID-19 mouse model are shown.(G) Representative images of the immunohistochemical analysis of p-MLKL and GSDMD in lung sections of mice are shown. Scale Bar = 50 µm. Values are presented as means ± SE. *p < 0.05, **p < 0.01, ***p < 0.0001.
Fig 3: Serum levels of markers of epithelial cell death and high-mobility group box (HMGB)-1 in serum samples of COVID-19 patients with or without acute respiratory distress syndrome (ARDS) and healthy controls(A-F) Levels of (A) CK18-M65, an epithelial total cell death marker, and (B) CK18-M30, an epithelial apoptosis marker; (C) CK18-M30/M65 ratio, an indicator of the fraction of epithelial cells undergoing apoptosis versus all types of cell death at admission (on the first or second hospital day). Temporal changes in (D) CK18-M65, (E) CK18-M30, and (F) CK18-M30/M65 ratio in sera of COVID-19 patients with ARDS.(G) HMGB-1 levels in serum samples of COVID-19 patients with or without ARDS and healthy controls are shown. Values are presented as medians and interquartile ranges. *p < 0.05, **p < 0.01, ***p < 0.0001.
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