GoKawiila. IB analysis of Aldh18a1 expression in lung, kidney, brain and spleen tissues from Aldh18a1+/+ and Aldh18a1−/− mice. b-g. Spermine level (b), representative livers and IHC images (c), percentage of liver-to-body weight ratio (d), serum ALT, AST and LDH level (unit per liter, U/L, e), relative GSH/GSSG ratio (f) and ROS (g) levels in livers of Aldh18a1+/+ and Aldh18a1−/− mice at 2 months of age. h. Left: schematic illustration of the experimental design. Right: IB analysis of Aldh18a1 expression in liver tissues, and the hepatic tumorigenesis incidence in DEN/CCl 4 mice injected with AAV-Vector or AAV-Aldh18a1 at each time point. i. Spermine and MDA level (right) in liver tissues from DEN/CCl 4 mice injected with AAV-Vector or AAV-Aldh18a1 at 4 m [n = 10 liver tissues (AAV-Vector), n = 6 tumor tissues (AAV-Aldh18a1)]. j, l. Left: schematic illustration of the experimental design. Right: IB analysis of Aldh18a1 expression in liver tissues, and the hepatic tumorigenesis incidence in LTsc1–/–Pten–/– mice (j), and DEN/CCl 4 mice (l) injected with AAV-shVector or AAV-shAldh18a1 with the indicated treatment at each time point. k. Spermine and MDA level in liver tissues from LTsc1–/–Pten–/– mice injected with AAV-shVector or AAV-shAldh18a1 with the indicated treatment at 20 w. n = 7 tumor tissues (AAV-shVector) [n = 10 liver tissues (AAV-shAldh18a1+Vehicle), n = 10 tumor tissues (AAV-shAldh18a1+Spm (50 mg/kg), n = 10 tumor tissues (AAV-shAldh18a1+Lip-1(10 mg/kg)]. m. Spermine and MDA level in liver tissues from DEN/CCl 4 mice injected with AAV-shVector or AAV-shAldh18a1 with the indicated treatments at 6 m [n = 7 tumor tissues (AAV-shVector), n = 10 liver tissues (AAV-shAldh18a1+Vehicle), n = 10 tumor tissues (AAV-shAldh18a1+Spm), n = 10 tumor tissues (AAV-shAldh18a1+Lip-1]. n, p. Left: schematic illustration of the experimental design. Right: the hepatic tumorigenesis incidence in LTsc1–/–Pten–/– mice (n), and DEN/CCl 4 mice (p) treated with Vehicle or YG1702 (45 mg/kg) with the indicated treatment at each time point. o. Spermine level (left) and MDA level (right) in liver tissues from LTsc1–/–Pten–/– mice treated with Vehicle or YG1702 with the indicated treatment at 20 w [n = 6 tumor tissues (Vehicle), n = 10 liver tissues (YG1702 + Vehicle), n = 10 tumor tissues (YG1702 + Spm), n = 10 tumor tissues (YG1702 + Lip-1]. q. Spermine and MDA level (right) in liver tissues from administered with Vehicle or YG1702 with the indicated treatments at 6 m [n = 7 tumor tissues (Vehicle), n = 10 liver tissues (YG1702+Vehicle), n = 10 tumor tissues (YG1702+Spm), n = 10 tumor tissues (YG1702+Lip-1]. Data are the mean ± s.d. of n = 10 (b, h-q), n = 7 (c-g) biologically independent samples. Statistical analysis was performed using an unpaired two-tailed Student’s t-test (b-g, i), one-way ANOVA, followed by Dunnett’s test (k, m, o, and q), two-tailed Fisher’s exact test (h, l, n, and p). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns, not significant. The exact P values are summarized in Supplementary Table 2.
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