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However, recent studies in metabolically competent HepaRG cell lines [23] and primary human hepatocytes [66] have confirmed that exposure to high levels of APAP result in GSH depletion, APAP protein adduct formation in mitochondria and organelle dysfunction accompanied by oxidant stress, resulting in necrotic cell death in human cells as demonstrated earlier in mouse models

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Multiple matrix components including distinct collagen types, fibronectin molecules, and hyaluronan networks interact with cellular receptors such as integrins and Cluster of differentiation 44 (CD44), activating signaling cascades that regulate cellular metabolism and inflammatory pathways (324)

Moreover, collecting baseline data via this measure is crucial in informing design of future measures that could enable us to set appropriate performance targets for PCHs