Fig 2: Etoposide damage does not increase Aß40 and Aß42 secretion in differentiated ReN GA2 neurons. A) Treatment schematic for differentiating ReN GA2 neurons and treatment with and without 10µM etoposide for 6 h and designated recovery times. (Schematic created in BioRender, 2021.) B) Immunofluorescent staining of ReN GA2 NPCs and 20-day differentiated neurons with antibodies for anti-MAP2 (neuron) and anti-Ki67 (proliferation marker). C) Percent secreted Aß40 and Aß42 relative to controls after 6 h etoposide treatment and designated recovery times. D) Aß42/Aß40 ratio calculated from raw values. Error bars represent means±SD of three separate experiments.

Fig 3: Postnatal age-dependent changes in the number of different types of small intestinal epithelial cells and proliferation markers in mice. (A) Representative fluorescent images for immunostained frozen sections of Lyz1-positive paneth cells, Ki67-positive proliferative cells, ChgA-positive enteroendocrine cells (red), and DAPI stained nuclei (blue), obtained from the postnatal mice small intestine (ileum). (20× magnification, scale bar = 50 µm). Quantification of paneth cells (B), proliferative cells (C) in the intestinal crypts, and enteroendocrine cells (D) in the villus of neonate mice. (Data are represented as means ± SD from =8 crypts or villus from 3 animals per age group. **p = 0.01, ***p = 0.001 and ****p = 0.0001; one-way ANOVA with Dunnett's multiple comparisons test and compared with 1 day).

Fig 4: RA-induced reduction of proliferation is less dramatic in sHIF + RA cells. SH-SY5Y cells were co-stained for the proliferative markers BrdU and Ki67. The amount of BrdU + cells in the undiff. A The group was higher than both sSCR + RA (B) and sHIF + RA (C) cells. However, inhibition of HIF-1a in sHIF + RA cells leads to a partial recovery of the proliferative status with an increased amount of BrdU positive cells than sSCR + RA (D). Amount of Ki67 + cells in the groups Undiff. (E), sSCR + RA (F) and sHIF + RA (G) followed the same pattern (H) as for BrdU +

Fig 5: Effect of OKN-007 on cell proliferation in IC3752 pGBM tumor bearing mice.Immunohistochemistry images of Ki-67 levels in untreated (A) and OKN-007-treated (B) IC3752 pGBM tumors. (C) Ki-67 LI was significantly lower (p < 0.05) in the OKN-007–R treated group (n = 4) than in the untreated group (n = 6). There was no significant difference between the Ki-67 LI of the OKN-007–NR (n = 2) and the untreated groups. Values are represented as means ± SD. Asterisks indicate statistically significant difference (*p < 0.05). n.s.: not statistically significant. Scale bar = 200 µm. Group comparisons: (1) UT vs. OKN-007 (R); (2) OKN-007 (R) vs. OKN-007 (NR); and (3) UT vs. OKN-007 (NR).