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While this might suggest a temporal association between BMAL1 driven transcription/translation of NRF2, we cannot be certain since BMAL1 and CLOCK can each separately bind to other proteins (40, 47) and NRF2 can transcribe genes involved in xenobiotic disposition, protection from electrophiles and general stress response (48, 49)

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Expectations should be adjusted accordingly, with longer protocol durations (8 to 12 weeks), potentially higher doses, and understanding that improvement may reach 70 to 90 percent of normal rather than complete resolution