Fig 2: The ROC curves of predicting for 28-day survival and Kaplan–Meier estimator analysis of MFG-E8 for 28 day survival. (A) Kaplan–Meier estimator analysis of MFG-E8 for 28-day survival. The cut off value of MFG-E8 for the estimated 28-day mortality of patients with sepsis was 3.86 ng/mL. (B) The ROC curves of MFG-E8 for the predicting 28-day mortality in patients with sepsis.

Fig 3: Serum MFG-E8 levels are decreased in patients with sepsis compared with healthy controls and are negatively correlated with disease severity. (A) Serum MFG-E8 levels in 100 septic patients and 30 normal individuals. Mean ± SEM, ***p < 0.001. (B) Correlation analysis of the Acute Physiology and Chronic Health Evaluation (APACHE) II score and serum MFG-E8 levels of septic patients. p = 0.0001. (C) Correlation analysis of procalcitonin (PCT) and serum MFG-E8 levels of septic patients. p = 0.0383. (D) MFG-E8 improves the survival in cecal ligation and puncture (CLP)-induced sepsis.

Fig 4: Mfge8 -/- mice represent decreased neural stem cell proliferation after cerebral ischemia.(A) DAPI, Nestin and BrdU immunofluorescent staining of the subventricular zone in mice. Wild type C57BL/6 (Wt) (a-c) and Mfge8 -/- mice (d-f) showed similar sham baseline neural stem cell proliferation (Nestin+ and BrdU+ cells). Wt mice (g-i) showed increased Nestin+ and BrdU+ staining compared with the Mfge8 -/- mice (j-l) at 7 days after tMCAO. Scale bar = 100 μm. (B) Representative merged profiling of DAPI, Nestin and BrdU positive cells showing considerable increase in Nestin+BrdU+ cells in Wt tMCAO mice than that of Mfge8 -/- tMCAO mice. (C) Quantification of the BrdU+Nestin+ cells showed that Wt and Mfge8 -/- sham mice had similar baseline numbers of proliferating neural stem cells. However, at 7 days post-tMCAO, Wt mice showed a 2.3-fold increase in BrdU+Nestin+ cells compared with Mfge8 -/- mice. Data are presented as mean ± SEM. *p<0.05 vs WT-Sham; #p<0.05 vs WT-tMCAO; n = 3/group.

Fig 5: MFG-E8 suppressed ferroptosis in CLP-induced septic mice. Liver glutathione (GSH) contents (A), liver malondialdehyde (MDA) contents (B) and liver ferrous (Fe2+) concentrations (C) were measured 24 h after CLP. (D,E) Western blot analysis of GPX4 in the liver of CLP-induced septic mice at 0, 12 and 24 h after CLP. n = 3, mean ± SEM. (F,G) Western blot analysis of GPX4 in the liver of CLP-induced septic mice 24 h after CLP with MFG-E8 treatment. n = 3, mean ± SEM. (*p < 0.05 versus sham group; #,*p < 0.05 versus CLP group; *p < 0.05, **p < 0.01, ***p < 0.001).