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The other ESVs shown in the figure were also significant but had smaller fold changes (Figure 6)

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Additionally, esculetin (20-80 mg/kg) inhibits tBCCAO-induced activation of the mitochondrial apoptosis pathway and autophagy in mice by reducing the expression levels of autophagy-related factors (such as Bnip3, Beclin1, Pink1 and parkin) and apoptosis-related factors (such as p53, Bax and caspase 3) by activating the Nrf2 signaling pathway (43)

Following these steps should minimize negative outcomes while maximizing positive side effects