CPX-351 does not promote intestinal pathology. Effects of the “7 + 3” combination or CPX-351 administration every 3 days for 3 times in C57BL/6 mice. Mice were evaluated for (A) clinical signs of morbidity, (B) intestinal length, and (C) histopathology (PAS staining) and epithelial damage (TUNEL assay and Ki-67 staining in the insets), intestinal permeability by (D) serum endotoxin, (E) Fluorescein isothiocyanate (FITC)–dextran fluorescence, and (F) bacterial translocation to mesenteric lymph nodes and liver, (G) fecal calprotectin and expression (by reverse transcription polymerase chain reaction) of genes associated with (H) epithelial barrier function, (I) inflammatory cytokines and NLRP3 and (J) adaptive T helper cell responses in the mesenteric lymph nodes and ileum. Yellow arrows indicate inflammatory foci (magnified in the insets). Data are representative of 2 or 3 independent experiments. Each in vivo experiment includes 4 to 6 mice per group. Data are represented as mean ± standard error of the mean (SEM). For immunofluorescence, nuclei were counterstained with Hoechst. Photographs were taken with a high-resolution microscope (Olympus BX51); original magnification ×20 (C, ileum; scale bar, 200 μm) and ×40 (C, colon; scale bar, 100 μm). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; treated vs untreated (None) mice and CPX-351 vs “7 + 3” treatment. One-way analysis of variance (ANOVA), Bonferroni multiple comparison test. ns, not significant.

CPX-351 does not promote intestinal pathology. Effects of the “7 + 3” combination or CPX-351 administration every 3 days for 3 times in C57BL/6 mice. Mice were evaluated for (A) clinical signs of morbidity, (B) intestinal length, and (C) histopathology (PAS staining) and epithelial damage (TUNEL assay and Ki-67 staining in the insets), intestinal permeability by (D) serum endotoxin, (E) Fluorescein isothiocyanate (FITC)–dextran fluorescence, and (F) bacterial translocation to mesenteric lymph nodes and liver, (G) fecal calprotectin and expression (by reverse transcription polymerase chain reaction) of genes associated with (H) epithelial barrier function, (I) inflammatory cytokines and NLRP3 and (J) adaptive T helper cell responses in the mesenteric lymph nodes and ileum. Yellow arrows indicate inflammatory foci (magnified in the insets). Data are representative of 2 or 3 independent experiments. Each in vivo experiment includes 4 to 6 mice per group. Data are represented as mean ± standard error of the mean (SEM). For immunofluorescence, nuclei were counterstained with Hoechst. Photographs were taken with a high-resolution microscope (Olympus BX51); original magnification ×20 (C, ileum; scale bar, 200 μm) and ×40 (C, colon; scale bar, 100 μm). ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; treated vs untreated (None) mice and CPX-351 vs “7 + 3” treatment. One-way analysis of variance (ANOVA), Bonferroni multiple comparison test. ns, not significant.

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