Fig 2: Schematic diagram showing the cytoprotective signaling associated with MET in MGO-induced endothelial cell apoptosis.The possible molecular mechanisms of MET in MGO-induced endothelial dysfunction in human ECs were explored. As depicted, MET inhibited the apoptotic signaling cascades initiated by MGO-generated ROS via modulating the PI3K/Akt and Nrf2/HO-1 signaling pathways. Furthermore, MET effectively exerts protective effects against MGO-induced oxidative stress, mitochondrial dysfunction, apoptosis, and inflammation in vitro and in vivo.

Fig 3: Ursodeoxycholic acid (UDCA) mitigated As(III)-induced LO2 hepatocytes apoptosis via Nrf2 activation. LO2 cells were transfected with Nrf2 siRNA for 48 h, and then incubated with UDCA, and then subjected to As(III) stimulation. (A) LO2 cells was evaluated by JC-10 staining under a fluorescence microscope. Scale bar: 100 µm (magnification 200×). Red and green fluorescence scanned by densitometer. Data are presented as Mean ± SEM (n = 3). The ratio of red to green fluorescence in cells were calculated (B) Induction of apoptosis was measured by Annexin-V/PI double staining was detected by flow cytometry. The apoptosis rate of Annexin-V/PI double-stained LO2 cells cells was calculated from flow cytometric analysis. (C) Hepatic levels of Cleaved Caspase-3, and 9, Cyto C, p53 and rate of Bax/Bcl-2 were analyzed by Western blotting with specific antibodies. Representative blots were shown. GAPDH was used as loading control. Data are presented as Mean ± SEM (n = 3). (D) Hepatic activities of Caspase-3, and 9 were also quantifified. Data are presented as Mean ± SEM (n = 6). Significant differences are shown as **P < 0.01, compared with the control group. # P < 0.05, ## P < 0.01, compared with the As(III) group. ++ P < 0.01, + P < 0.05, compared with the As(III)+UDCA group.

Fig 4: Oridonin improves LSS induced EC dysfunction and oxidative stress by activating NRF2. A-C Results of the western blot revealed that oridonin treatment counteracted the LSS-induced downregulation of eNOS and SOD by activating NRF2. ##P < 0.01 vs. LSS (-) + oridonin (-) + NRF2 siRNA (-); **P < 0.01 vs. LSS (+) + oridonin (-) + NRF2 siRNA (-); $$P < 0.01 vs. LSS (+) + oridonin (+) + NRF2 siRNA (-). LSS, low shear stress; eNOS, endothelial nitric oxide synthase; SOD, superoxide dismutase; siRNA, small interfering RNA

Fig 5: iASPP-Nrf2-M-CSF regulates M2 polarization in vitro.A Schematic of the experimental strategies used to trigger macrophage polarization. B–E Expression levels of CD86 and CD206 were detected by flow cytometry in HCT116 cells after iASPP OE (B, C), and iASPP and/or Nrf2 KD (D, E) with and without Dox and/or BLZ945 treatments. The quantification of the ratio of M2/M1 (CD206/CD86) is calculated and shown in bar graphs (C, E). Values are mean ± SD from three independent experiments; *P < 0.05, **P < 0.01, compared with DMSO (C, E); #P < 0.05, ##P < 0.01, compared with Dox -treated control (C, E); $P < 0.05, $$P < 0.01, compared with Dox and BLZ945-treated control (C, E); N.S., not significant (C, E).