Fig 2: Inhibition of Bax translocation by RasGRP2 via R-Ras-PI3K-Akt signaling pathway. (a–d) Each effect was detected by western blotting. (a) Phosphorylation of JNK was detected using a specific antibody. Cells were incubated with or without TNF-a, anisomycin, or BAM7 for 1 h. (b) Activated Bax was isolated by immunoprecipitation (IP) using a Bax (6A7) antibody. Cells were incubated with or without BAM7 or anisomycin for 16 h. (c,d) Cytosolic and mitochondrial fractions were isolated by cell fractionation kit. (d) Cells were pre-treated with siRNAs against R-Ras or negative control siRNA and incubated with or without BAM7 for 16 h. M: mock cells, R: RasGRP2-stable overexpression cells, aniso: anisomycin, IP: immunoprecipitation.

Fig 3: Relative expression of ERß (A), PI3K (B), p-PI3K (C), Akt (D), p-Akt (E) and an internal reference (a–tubulin) (F) in MIRI-LVR rats treated with high-dose of GXDSF treated group and PHTPP. Compared with the sham group: ##P < 0.01. Compared with the MIRI-LVR model group: *P < 0.05, **P < 0.01, ***P < 0.001. Compared with the high-dose of GXDSF treated group: &&&P < 0.001. The data are presented as the mean ± SD (n = 6 in each group).

Fig 4: PRMT6-pAKT axis is crucial in CSE-induced epithelia death. Cigarette smoke reduces PRMT6 at both mRNA and protein levels. Decreased PRMT6 promotes PI3Kp85 expression and increases the protein stability of PTEN. Changes of PI3Kp85 and PTEN, as well as decreased PDK1, reduce the total phosphorylation level of AKT. Lower level of AKT phosphorylation in turn promotes cigarette smoke-induced lung epithelial cell death.

Fig 5: HFP promotes PD in mice. (a) Ctrl and HFD mice, (b and c) the percentage changes of bodyweight (12 weeks), and weight gain ([the final body weight (23 weeks) - the primary bodyweight (12 weeks)]). (d-g) Plasma Biochemical Analysis including (d and e) fasting blood glucose (FBG) concentration, glucose tolerance test (GTT), and the area under the curve (AUC) in Ctrl and HFD groups. (f) Plasma insulin concentration and (g) HOMA index in Ctrl and HFD groups. (h) Immunoblot analyses of liver lysates for protein level evaluations such as p-AKT and total AKT in Ctrl and HFD groups. All values are presented as mean ± SD. * = p < 0.05 and *** = p < 0.001 indicate significant statistical differences in HFD compared to Ctrl mice.