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Grant Abstract: Age and Diet: Major interacting factors that drive sporadic intestinal cancer

Grant Number: 5R01CA174432-02
PI Name: Augenlicht
Project Title: Age and Diet: Major interacting factors that drive sporadic intestinal cancer

Abstract: Specific Aims for the supplemental research:
The overall objective of this supplemental research is to determine whether (–)-epicatechin treatment after ICH improves histologic and functional outcomes in young female and aged male and female mice and the role of Nrf2 signaling. In two specific aims, we will test the hypothesis that the flavonoid (–)-epicatechin reduces ICH injury through the Nrf2 pathway.
Aim 1: To determine whether post-treatment with the optimal dose of (–)-epicatechin is effective in young female and aged male and female mice. Because sex differences and aging affect ICH outcomes, we will use the blood ICH model to investigate the efficacy of (–)-epicatechin for improving early and long-term ICH outcomes in young female and aged male and female animals. The research design will be the same as that in the parent R01; we will only add more male and female animals to increase statistical power and enable us to determine sex differences in the efficacy of (–)-epicatechin for treating ICH.
Aim 2: To determine whether the Nrf2 pathway contributes to the neuroprotective effect of (–)- epicatechin in in vitro models of hemoglobin-induced toxicity. Because (–)-epicatechin may act by stimulating the transcription factor Nrf2, we will examine whether Nrf2 is required for the neuroprotective effect of (–)-epicatechin in an in vitro model of organotypic hippocampal slice cultures (OHSCs) treated with hemoglobin. The research design will be the same as that in the parent R01. Sex-stratified OHSCs from C57BL/6 wild-type (WT) and Nrf2-/- mice will be used to determine whether sex affects the efficacy of (–)- epicatechin in vitro and the role of Nrf2.


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