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Abbreviations DNBS: 2,4,6-Dinitrobenzene sulfonic acid 5-ASAs: 5-Aminosalicylates ACC: Acetyl CoA carboxylase ATP: Adenosine triphosphate AMPK: Adenosine monophosphate-activated protein kinase AGE: Advanced glycation end products AGIs: Alpha-glucosidase inhibitors -LA: Alpha-lipoic acid SMA: Alpha Smooth Muscle Actin AnxA1: Annexin A1 ARE: Antioxidant response element Bcl: B cell lymphoma BADGE: Bisphenol A diglycidyl ether CCR2: C-C motif chemokine ligand 2 CCL11: C-C motif chemokine 11 CRP: C-reactive protein COPD: Chronic obstructive pulmonary disease CD: Crohns disease COX: Cyclooxygenase CMDI: Colonic Mucosa Damage Index DAMP: Damage-associated molecular pattern DSS: Dextran sodium sulfate DM: Diabetes mellitus DPP4Is: Dipeptidyl peptidase-4 inhibitors DAI: Disease activity index GI: Gastrointestinal tract GLP: Glucagon-like peptide GSH: Glutathione GPX: Glutathione peroxidase HES1: Hairy and enhancer of split type-1 HSP: Heat shock protein HO-1: Heme oxygenase HMGB1: High mobility group box 1 IBD: Inflammatory bowel diseases ICAM-1: Intercellular adhesion molecule IFNs: Interferons IL: Interleukin JNK: Jun N-terminal kinase Keap1: Kelchike ECH-associated protein 1 KLF: Krppel-like factor 4 LPMC: Lamina propria mononuclear cells LPS: Lipopolysaccharides MDA: Malonaldehyde mTOR: Mammalian target of rapamycin MKK: MAP kinase kinase MMP: Matrix metalloproteinase MCP: Monocyte chemoattractant protein MPO: Myeloperoxidase NIK: NF-B-inducing kinase NAFLD: Non-alcoholic fatty liver disease Nrf2: Nuclear factor erythroid 2-related factor 2 NF-B: Nuclear factor kappa B NLRP3: Nucleotide-binding domain, leucine-richcontaining family, pyrin domaincontaining-3 ERK: P-Extracellular signal-regulated kinase MAPK: P38 mitogen-activated protein kinases PAMP: Pathogen-associated molecular pattern PPAR: Peroxisome proliferator-activator receptor gamma PGC-1: Peroxisome proliferator-activated receptor gamma coactivator-1 PCNA: Proliferating cell nuclear antigen PTZ: Pioglitazone PI3K: Phosphatidylinositol 3-kinase AKT: Protein kinase B RNS: Reactive nitrogen species ROS: Reactive oxygen species RAGE: Receptor for advanced glycation end-products RTZ: Rosiglitazone SPDEF: SAM pointed domain-containing Ets transcription factor STAT: Signal transducer and activator of transcription Smad: Small Mothers Against Decapentaplegic SGLT: Sodium-glucose cotransporters SGLT2I: Sodium-glucose cotransporter-2 inhibitor SPHK1: Sphingosine kinase 1 S1P: Sphingosine 1 phosphate SUs: Sulfonylureas SOD: Superoxide dismutase TZDs: Thiazolidinediones TBARS: Thio barbituric acid-reactive substances TLR: Toll-like receptors TGF-: Transforming growth factor beta TNF: Tumor necrosis factor T1DM: Type-1 DM T2DM: Type-2 DM UC: Ulcerative colitis WT: Wild type ZO-1: Zonula occludens-1 References Allin KH, Jensen CB, Jacobsen RK, Jess T (2022) Metformin use is not associated with reduced risk of older onset inflammatory bowel disease: a Danish nationwide population-based study

performed bioinformatics analysis using multiple machine learning methods on the GEO database and identified three pivotal cuproptosis-related genes (CRGs): NFE2L2, DLD and POLD1