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Consequently, HIF-1 has been shown to upregulate NQO1 expression in response to stressful events, such as hypoxia

10.1152/physrev.00010.2018 28 BhattiJ

Introducing a second agent with a different mechanism can restart progress by circumventing the specific adaptations the body made in response to the first compound

Thus, oxidative damage in depression and anxiety disorders can aect the amygdala and hippocampus (Salim, 2017), among other brain structures, reduce neurogenesis (Hassan et al., 2014;van Velzen et al., 2017), and contribute to cognitive dysfunction (Duy et al., 2014)