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Finally, at the 96th h, it was found that the expression of HO-1 reached at a minimum value, and the oxidative stress index (OSI) of fibroblasts was increased, collagen synthesis of fibroblasts was reduced, proliferation and migration were supressed, and apoptosis was increased (Li et al., 2018)

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Starkschall G, Britton K, McAleer MF, Jeter MD, Kaus MR, Bzdusek K, Mohan R , Cox JD

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Classical antifolate drugs, including methotrexate (targeting DHFR) [153] and fluoropyrimidine agents (targeting TYMS) [154], induce cell death in rapidly proliferating malignancies by specifically inhibiting key enzymes in 1 C metabolism, thereby depleting nucleotide pools and causing replication stress [101]

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