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Furthermore, SFN may activate Nrf2 by initiating the transcription of trigger receptor expressed on myeloid cells-2 (TREM2) in the medial PFC (mPFC), increasing the expression of the M2 microglial marker arginase 1 (ARG1), which may alleviate depressive phenotypes through its anti-inflammatory and neuroprotective functions (He et al., 2022)

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If a patient had discontinued metformin use for longer than 6 months, the duration of metformin treatment was counted from when it was resumed