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Keywords: MOTS-c, mitochondrial-derived peptide, therapeutic exploitation, synthetic biology, endocrine Introduction Mitochondria are organelles produced by archaea that are required for the production of ATP (1)

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1 Introduction Ulcerative colitis (UC) is a chronic, relapsing form of inflammatory bowel disease (IBD) characterized by immune system dysfunction and pathological overactivation of mucosal immune responses, leading to persistent inflammation and subsequent colonic mucosal injury ( Sirtuins (SIRTs) represent a family of evolutionarily conserved enzymes that are dependent on NAD + , categorized into seven distinct members (SIRT1 through SIRT7) ( + -dependent deacetylase sirtuin-1 (SIRT1) meticulously regulates a variety of substrates, such as histone and non-histone proteins, thereby producing significant effects on metabolic homeostasis, apoptosis regulation, inflammatory responses, attenuation of oxidative stress, and even the aging process ( Signal transducer and activator of transcription 3 (STAT3), a crucial cytoplasmic transcription factor in the STAT family, consists of 770 amino acids and possesses a complex domain structure, facilitating its diverse roles in cell signaling and gene regulation ( Short peptides are distinctive biomolecules that combine the benefits of traditional small molecules and mature proteins, offering new, more effective therapeutic agents with fewer side effects ( 2+ affinity comparable to that of albumin’s copper transport sites, forming an in vivo complex, glycyl-L-histidyl-L-lysine-Cu 2+ (GHK-Cu), which enhances its bioavailability (Figure 1A