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At the mechanistic level, betaine may exert a cardioprotective effect by inhibiting oxidative stress, inflammation, and fibrosis by regulating the AMPK/nuclear factor erythroid 2-related factor 2 (Nrf2)/TGF-β signaling pathway (24), and enhance pulmonary hypertension and ischemia-reperfusion injury in animal models (Figure 6A)

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Likewise, direct injury of RPE cells via cigarette smoke-induced oxidative stress has been demonstrated in mice, which developed RPE apoptosis and basal drusen-like deposits after an exposition of 6 months [261]