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For instance, in M1 pro-inflammatory macrophages (Ms), there is a metabolic break at isocitrate dehydrogenase in the TCA cycle due to suppression of its mRNA expression, leading to the accumulation of citrate and itaconate, which drive lipid synthesis and stabilization of anti-inflammatory transcription factors, such as nuclear factor-erythroid factor 2-related factor 2 (NRF2) and activating transcription factor 3 ( Unlike nicotinamide adenine dinucleotide (NAD + ), nicotinamide adenine dinucleotide phosphate (NADP + ) has an additional phosphate on the 2 position of the ribose ring that attaches to an adenine moiety and has a lower intracellular concentration than NAD + ( Figure 1A )