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Although we do not have direct mechanistic evidence to explain why chronic administration of ximelagatran leads to increased hepatotoxicity compared with short-term treatment, our data demonstrate that the human serum-derived educated spheroid system can capture ximelagatran-mediated DILI under chronic exposure conditions, but not under acute treatment, closely mirroring the clinical observations in humans

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Dietary non-heme iron primarily exists in an oxidized (Fe 3+ ) form that is not bioavailable and must first be reduced to the Fe 2+ form by a ferrireductase enzyme, which uses vitamin C as a coenzyme, before being transported across the intestinal epithelium

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