|
1
|
Wang Y, Huang Y, Chase RC, Li T, Ramai D, Li S, Huang X, Antwi SO, Keaveny AP and Pang M: Global burden of digestive diseases: A systematic analysis of the global burden of diseases study, 1990 to 2019. Gastroenterology. 165:773–783.e15. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
2
|
Chen HY, Ge P, Liu JY, Qu JL, Bao F, Xu CM, Chen HL, Shang D and Zhang GX: Artificial intelligence: Emerging player in the diagnosis and treatment of digestive disease. World J Gastroenterol. 28:2152–2162. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
3
|
Edgington-Mitchell LE: Pathophysiological roles of proteases in gastrointestinal disease. Am J Physiol Gastrointest Liver Physiol. 310:G234–G239. 2016. View Article : Google Scholar
|
|
4
|
Shinomura Y: Preface. Recent advances in the diagnosis and treatment of gastrointestinal diseases. Digestion. 91:5–6. 2015. View Article : Google Scholar : PubMed/NCBI
|
|
5
|
Peery AF, Crockett SD, Murphy CC, Lund JL, Dellon ES, Williams JL, Jensen ET, Shaheen NJ, Barritt AS, Lieber SR, et al: Burden and cost of gastrointestinal, liver, and pancreatic diseases in the United States: Update 2018. Gastroenterology. 156:254–272.e11. 2019. View Article : Google Scholar
|
|
6
|
Ivány E, Farkas B, Bacsur P, Rutka M, Gálfalvi N, Farkas K, Szepes Z and Molnár T: A narrative review on the frequency, pathophysiology and management of bowel urgency associated with ulcerative colitis. Best Pract Res Clin Gastroenterol. 78:1020612025. View Article : Google Scholar : PubMed/NCBI
|
|
7
|
Singh M, Morris VK, Bandey IN, Hong DS and Kopetz S: Advancements in combining targeted therapy and immunotherapy for colorectal cancer. Trends Cancer. 10:598–609. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
8
|
Reichert M, Willis F, Post S, Schneider M, Vilz T, Willis M and Hecker A: Pharmacologic prevention and therapy of postoperative paralytic ileus after gastrointestinal cancer surgery: Systematic review and meta-analysis. Int J Surg. 110:4329–4341. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
9
|
Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC, Rabinowitz JD and Roberts MF: Itaconic acid is a mammalian metabolite induced during macrophage activation. J Am Chem Soc. 133:16386–16389. 2011. View Article : Google Scholar : PubMed/NCBI
|
|
10
|
Shi J and Cai C: Research progress on the mechanism of itaconate regulating macrophage immunometabolism. Front Immunol. 13:9372472022. View Article : Google Scholar : PubMed/NCBI
|
|
11
|
Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, Binz T, Wegner A, Tallam A, Rausell A, et al: Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci USA. 110:7820–7825. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
12
|
Peace CG and O'Neill LA: The role of itaconate in host defense and inflammation. J Clin Invest. 132:e1485482022. View Article : Google Scholar : PubMed/NCBI
|
|
13
|
Zasłona Z and O'Neill LAJ: Cytokine-like roles for metabolites in immunity. Mol Cell. 78:814–823. 2020. View Article : Google Scholar
|
|
14
|
Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, et al: Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 556:113–117. 2018. View Article : Google Scholar : PubMed/NCBI
|
|
15
|
Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, Ruzek MC, Slivka PF, McGettrick AF, Banahan K, et al: The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 32:468–478.e7. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
16
|
Farré R, Fiorani M, Abdu Rahiman S and Matteoli G: Intestinal permeability, inflammation and the role of nutrients. Nutrients. 12:11852020. View Article : Google Scholar : PubMed/NCBI
|
|
17
|
Yang W, Wang Y, Wang T, Li C, Shi L, Zhang P, Yin Y, Tao K and Li R: Protective effects of IRG1/itaconate on acute colitis through the inhibition of gasdermins-mediated pyroptosis and inflammation response. Genes Dis. 10:1552–1563. 2022. View Article : Google Scholar
|
|
18
|
Li Y, Xu Y, Li W, Li J, Wu W, Kang J, Jiang H, Liu P, Liu J, Gong W, et al: Itaconate inhibits SYK through alkylation and suppresses inflammation against hvKP induced intestinal dysbiosis. Cell Mol Life Sci. 80:3372023. View Article : Google Scholar : PubMed/NCBI
|
|
19
|
Huang Y, Yang W, Yang L, Wang T, Li C, Yu J, Zhang P, Yin Y, Li R and Tao K: Nrf2 inhibition increases sensitivity to chemotherapy of colorectal cancer by promoting ferroptosis and pyroptosis. Sci Rep. 13:143592023. View Article : Google Scholar : PubMed/NCBI
|
|
20
|
Baup S: Ueber eine neue Pyrocitronsäure, und über Zusammensetzung der Citronensäure [On a new pyrocitric acid, and on the composition of citric acid]. Ann Pharmacie. 19:29–38. 1836.In German. View Article : Google Scholar
|
|
21
|
Kinoshita K: Über eine neue Aspergillus-Art, Asp. itaconicus nov. spec. [About a new Aspergillus species, Asp. itaconicus nov. spec.]. Shokubutsugaku Zasshi (Botanical Magazine Tokyo). 45:45–61. 1931.In German, Japanese. View Article : Google Scholar
|
|
22
|
Willke T and Vorlop KD: Biotechnological production of itaconic acid. Appl Microbiol Biotechnol. 56:289–295. 2001. View Article : Google Scholar : PubMed/NCBI
|
|
23
|
Shin JH, Yang JY, Jeon BY, Yoon YJ, Cho SN, Kang YH, Ryu DH and Hwang GS: 1H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J Proteome Res. 10:2238–2247. 2011. View Article : Google Scholar : PubMed/NCBI
|
|
24
|
O'Neill LAJ and Artyomov MN: Itaconate: The poster child of metabolic reprogramming in macrophage function. Nat Rev Immunol. 19:273–281. 2019. View Article : Google Scholar : PubMed/NCBI
|
|
25
|
Teleky BE and Vodnar DC: Biomass-derived production of itaconic acid as a building block in specialty polymers. Polymers (Basel). 11:10352019. View Article : Google Scholar : PubMed/NCBI
|
|
26
|
Shi X, Zhou H, Wei J, Mo W, Li Q and Lv X: The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases. Redox Biol. 58:1025532022. View Article : Google Scholar : PubMed/NCBI
|
|
27
|
Wang Q, Li XL, Mei Y, Ye JC, Fan W, Cheng GH, Zeng MS and Feng GK: The anti-inflammatory drug dimethyl itaconate protects against colitis-associated colorectal cancer. J Mol Med (Berl). 98:1457–1466. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
28
|
Anderson NM, Mucka P, Kern JG and Feng H: The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell. 9:216–237. 2018. View Article : Google Scholar :
|
|
29
|
Orecchioni M, Ghosheh Y, Pramod AB and Ley K: Macrophage polarization: Different gene signatures in M1(LPS+) vs classically and M2(LPS-) vs alternatively activated macrophages. Front Immunol. 10:10842019. View Article : Google Scholar
|
|
30
|
Gordon S and Martinez FO: Alternative activation of macrophages: Mechanism and functions. Immunity. 32:593–604. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
31
|
Feng J, Li C, He H, Xu S, Wang X and Chen K: Construction of cell factory through combinatorial metabolic engineering for efficient production of itaconic acid. Microb Cell Fact. 21:2752022. View Article : Google Scholar : PubMed/NCBI
|
|
32
|
Li Y, Gong W, Li W, Liu P, Liu J, Jiang H, Zheng T, Wu J, Wu X, Zhao Y and Ren J: The IRG1-itaconate axis: A regulatory hub for immunity and metabolism in macrophages. Int Rev Immunol. 42:364–378. 2023. View Article : Google Scholar
|
|
33
|
Wu R, Chen F, Wang N, Tang D and Kang R: ACOD1 in immunometabolism and disease. Cell Mol Immunol. 17:822–833. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
34
|
Lee CG, Jenkins NA, Gilbert DJ, Copeland NG and O'Brien WE: Cloning and analysis of gene regulation of a novel LPS-inducible cDNA. Immunogenetics. 41:263–270. 1995. View Article : Google Scholar : PubMed/NCBI
|
|
35
|
Degrandi D, Hoffmann R, Beuter-Gunia C and Pfeffer K: The proinflammatory cytokine-induced IRG1 protein associates with mitochondria. J Interferon Cytokine Res. 29:55–67. 2009. View Article : Google Scholar
|
|
36
|
Kang H, Liu T, Wang Y, Bai W, Luo Y and Wang J: Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome. Cell Mol Immunol. 21:689–706. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
37
|
Hall CJ, Boyle RH, Astin JW, Flores MV, Oehlers SH, Sanderson LE, Ellett F, Lieschke GJ, Crosier KE and Crosier PS: Immunoresponsive gene 1 augments bactericidal activity of macrophage-lineage cells by regulating β-oxidation-dependent mitochondrial ROS production. Cell Metab. 18:265–278. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
38
|
Runtsch MC, Angiari S, Hooftman A, Wadhwa R, Zhang Y, Zheng Y, Spina JS, Ruzek MC, Argiriadi MA, McGettrick AF, et al: Itaconate and itaconate derivatives target JAK1 to suppress alternative activation of macrophages. Cell Metab. 34:487–501.e8. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
39
|
Li Y, Li YC, Liu XT, Zhang L, Chen YH, Zhao Q, Gao W, Liu B, Yang H and Li P: Blockage of citrate export prevents TCA cycle fragmentation via Irg1 inactivation. Cell Rep. 38:1103912022. View Article : Google Scholar : PubMed/NCBI
|
|
40
|
De Souza DP, Achuthan A, Lee MK, Binger KJ, Lee MC, Davidson S, Tull DL, McConville MJ, Cook AD, Murphy AJ, et al: Autocrine IFN-I inhibits isocitrate dehydrogenase in the TCA cycle of LPS-stimulated macrophages. J Clin Invest. 129:4239–4244. 2019. View Article : Google Scholar : PubMed/NCBI
|
|
41
|
Ganta VC, Choi MH, Kutateladze A, Fox TE, Farber CR and Annex BH: A MicroRNA93-interferon regulatory factor-9-immunoresponsive gene-1-itaconic acid pathway modulates M2-like macrophage polarization to revascularize ischemic muscle. Circulation. 135:2403–2425. 2017. View Article : Google Scholar : PubMed/NCBI
|
|
42
|
Huang J, Jiang Y, Ji R, Jia Y, Wang S, Zhou Z, Wang S, Wang J, Yang Q, Bai H, et al: Macrophage scavenger receptor A1 antagonizes abdominal aortic aneurysm via upregulating IRG1. Biochem Pharmacol. 213:1156312023. View Article : Google Scholar : PubMed/NCBI
|
|
43
|
Scheurlen KM, Chariker JH, Kanaan Z, Littlefield AB, George JB, Seraphine C, Rochet A, Rouchka EC and Galandiuk S: The NOTCH4-GATA4-IRG1 axis as a novel target in early-onset colorectal cancer. Cytokine Growth Factor Rev. 67:25–34. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
44
|
Schuster EM, Epple MW, Glaser KM, Mihlan M, Lucht K, Zimmermann JA, Bremser A, Polyzou A, Obier N, Cabezas-Wallscheid N, et al: TFEB induces mitochondrial itaconate synthesis to suppress bacterial growth in macrophages. Nat Metab. 4:856–866. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
45
|
Larsen H and Eimhjellen KE: The mechanism of itaconic acid formation by Aspergillus terreus. 1. The effect of acidity. Biochem J. 60:135–139. 1955. View Article : Google Scholar : PubMed/NCBI
|
|
46
|
Cheah HL, Lim V and Sandai D: Inhibitors of the glyoxylate cycle enzyme ICL1 in Candida albicans for potential use as antifungal agents. PLoS One. 9:e959512014. View Article : Google Scholar : PubMed/NCBI
|
|
47
|
Otten A, Brocker M and Bott M: Metabolic engineering of Corynebacterium glutamicum for the production of itaconate. Metab Eng. 30:156–165. 2015. View Article : Google Scholar : PubMed/NCBI
|
|
48
|
Lee CB, Šnajdr I, Tenora L, Alt J, Gori S, Krečmerová M, Maragakis RM, Paule J, Tiwari S, Iyer J, et al: Discovery of orally available prodrugs of itaconate and derivatives. J Med Chem. 68:3433–3444. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
49
|
Willenbockel HF, Williams AT, Lucas A, Reynolds MB, Joulia E, Ruchhoeft ML, Dowerg B, Cabrales P, Metallo CM and Cordes T: In vivo itaconate tracing reveals degradation pathway and turnover kinetics. Nat Metab. 7:1781–1790. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
50
|
Cooper RA and Kornberg HL: The utilization of itaconate by Pseudomonas sp. Biochem J. 91:82–91. 1964. View Article : Google Scholar : PubMed/NCBI
|
|
51
|
Adler J, Wang SF and Lardy HA: The metabolism of itaconic acid by liver mitochondria. J Biol Chem. 229:865–879. 1957. View Article : Google Scholar : PubMed/NCBI
|
|
52
|
Fan Y, Dan W, Wang Y, Ma Z, Jian Y, Liu T, Li M, Wang Z, Wei Y, Liu B, et al: Itaconate transporter SLC13A3 confers immunotherapy resistance via alkylation-mediated stabilization of PD-L1. Cell Metab. 37:514–526.e5. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
53
|
Liu X, Shi B, Suo R, Xiong S, Wang X, Liang X, Li X and Li G: Itaconate regulates macrophage function through stressful iron-sulfur cluster disrupting and iron metabolism rebalancing. FASEB J. 35:e219362021. View Article : Google Scholar : PubMed/NCBI
|
|
54
|
Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD and Yamamoto M: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13:76–86. 1999. View Article : Google Scholar : PubMed/NCBI
|
|
55
|
Rodríguez-Prados JC, Través PG, Cuenca J, Rico D, Aragonés J, Martín-Sanz P, Cascante M and Boscá L: Substrate fate in activated macrophages: A comparison between innate, classic, and alternative activation. J Immunol. 185:605–614. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
56
|
Qin W, Qin K, Zhang Y, Jia W, Chen Y, Cheng B, Peng L, Chen N, Liu Y, Zhou W, et al: S-glycosylation-based cysteine profiling reveals regulation of glycolysis by itaconate. Nat Chem Biol. 15:983–991. 2019. View Article : Google Scholar : PubMed/NCBI
|
|
57
|
Aso K, Kono M, Kanda M, Kudo Y, Sakiyama K, Hisada R, Karino K, Ueda Y, Nakazawa D, Fujieda Y, et al: Itaconate ameliorates autoimmunity by modulating T cell imbalance via metabolic and epigenetic reprogramming. Nat Commun. 14:9842023. View Article : Google Scholar : PubMed/NCBI
|
|
58
|
Bardi GT, Smith MA and Hood JL: Melanoma exosomes promote mixed M1 and M2 macrophage polarization. Cytokine. 105:63–72. 2018. View Article : Google Scholar : PubMed/NCBI
|
|
59
|
Soto-Heredero G, Gómez de Las Heras MM, Gabandé-Rodríguez E, Oller J and Mittelbrunn M: Glycolysis-a key player in the inflammatory response. FEBS J. 287:3350–3369. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
60
|
Wang F, Wang K, Xu W, Zhao S, Ye D, Wang Y, Xu Y, Zhou L, Chu Y, Zhang C, et al: SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1β production and to prevent DSS-induced colitis in mice. Cell Rep. 19:2331–2344. 2017. View Article : Google Scholar : PubMed/NCBI
|
|
61
|
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, et al: Succinate is a danger signal that induces IL-1β via HIF-1α. Nature. 496:238–242. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
62
|
Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, et al: Itaconate links inhibition of succinate dehydrogenase with macrophage metabolic remodeling and regulation of inflammation. Cell Metab. 24:158–166. 2016. View Article : Google Scholar : PubMed/NCBI
|
|
63
|
An L, Zhai Q, Tao K, Xiong Y, Ou W, Yu Z, Yang X, Ji J and Lu M: Quercetin induces itaconic acid-mediated M1/M2 alveolar macrophages polarization in respiratory syncytial virus infection. Phytomedicine. 130:1557612024. View Article : Google Scholar : PubMed/NCBI
|
|
64
|
Blanco LP, Patino-Martinez E, Nakabo S, Zhang M, Pedersen HL, Wang X, Carmona-Rivera C, Claybaugh D, Yu ZX, Desta E and Kaplan MJ: Modulation of the itaconate pathway attenuates murine lupus. Arthritis Rheumatol. 74:1971–1983. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
65
|
Muri J, Wolleb H, Broz P, Carreira EM and Kopf M: Electrophilic Nrf2 activators and itaconate inhibit inflammation at low dose and promote IL-1β production and inflammatory apoptosis at high dose. Redox Biol. 36:1016472020. View Article : Google Scholar
|
|
66
|
Ramalho T, Assis PA, Ojelabi O, Tan L, Carvalho B, Gardinassi L, Campos O, Lorenzi PL, Fitzgerald KA, Haynes C, et al: Itaconate impairs immune control of Plasmodium by enhancing mtDNA-mediated PD-L1 expression in monocyte-derived dendritic cells. Cell Metab. 36:484–497.e6. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
67
|
Burczyk G, Cichon I and Kolaczkowska E: Itaconate suppresses formation of neutrophil extracellular traps (NETs): Involvement of hypoxia-inducible factor 1α (Hif-1α) and heme oxygenase (HO-1). Front Immunol. 13:8646382022. View Article : Google Scholar
|
|
68
|
Fousert E, Toes R and Desai J: Neutrophil extracellular traps (NETs) take the central stage in driving autoimmune responses. Cells. 9:9152020. View Article : Google Scholar : PubMed/NCBI
|
|
69
|
Romagnani S: Th1/Th2 cells. Inflamm Bowel Dis. 5:285–294. 1999. View Article : Google Scholar : PubMed/NCBI
|
|
70
|
Kuo PC, Weng WT, Scofield BA, Paraiso HC, Brown DA, Wang PY, Yu IC and Yen JH: Dimethyl itaconate, an itaconate derivative, exhibits immunomodulatory effects on neuroinflammation in experimental autoimmune encephalomyelitis. J Neuroinflammation. 17:1382020. View Article : Google Scholar : PubMed/NCBI
|
|
71
|
Tomlinson KL, Lung TWF, Dach F, Annavajhala MK, Gabryszewski SJ, Groves RA, Drikic M, Francoeur NJ, Sridhar SH, Smith ML, et al: Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation. Nat Commun. 12:13992021. View Article : Google Scholar : PubMed/NCBI
|
|
72
|
Mcfadden BA and Purohit S: Itaconate, an isocitrate lyase-directed inhibitor in Pseudomonas indigofera. J Bacteriol. 131:136–144. 1977. View Article : Google Scholar : PubMed/NCBI
|
|
73
|
Hillier S and Charnetzky WT: Glyoxylate bypass enzymes in Yersinia species and multiple forms of isocitrate lyase in Yersinia pestis. J Bacteriol. 145:452–458. 1981. View Article : Google Scholar : PubMed/NCBI
|
|
74
|
Breen P, Zimbric M and Caverly LJ: Itaconic acid inhibits nontuberculous mycobacterial growth in pH dependent manner while 4-octyl-itaconic acid enhances THP-1 clearance of nontuberculous mycobacteria in vitro. PLoS One. 19:e03035162024. View Article : Google Scholar : PubMed/NCBI
|
|
75
|
Huang EY, Kwai BXC, Bhusal RP, Bashiri G and Leung IKH: Mycobacterium tuberculosis Rv1916 is an Acetyl-CoA-binding protein. Chembiochem. 24:e2023001622023. View Article : Google Scholar : PubMed/NCBI
|
|
76
|
Priya M, Gupta SK, Koundal A, Kapoor S, Tiwari S, Kidwai S, Sorio de Carvalho LP, Thakur KG, Mahajan D, Sharma D, et al: Itaconate mechanism of action and dissimilation in Mycobacterium tuberculosis. Proc Natl Acad Sci USA. 122:e24231141222025. View Article : Google Scholar : PubMed/NCBI
|
|
77
|
Liu Z, Liu D and Wang C: In situ chemoproteomic profiling reveals itaconate inhibits de novo purine biosynthesis in pathogens. Cell Rep. 43:1147372024. View Article : Google Scholar : PubMed/NCBI
|
|
78
|
Wang X, Menezes CJ, Jia Y, Xiao Y, Venigalla SSK, Cai F, Hsieh MH, Gu W, Du L, Sudderth J, et al: Metabolic inflexibility promotes mitochondrial health during liver regeneration. Science. 384:eadj43012024. View Article : Google Scholar : PubMed/NCBI
|
|
79
|
Zhao R, Xu L, Chen J, Yang Y, Guo X, Dai M, Tian GB and Qin LN: Itaconate induces tolerance of Staphylococcus aureus to aminoglycoside antibiotics. Front Microbiol. 15:14500852024. View Article : Google Scholar : PubMed/NCBI
|
|
80
|
Zhang B, Ku X, Zhang X, Zhang Y, Chen G, Chen F, Zeng W, Li J, Zhu L and He Q: The AI-2/luxS quorum sensing system affects the growth characteristics, biofilm formation, and virulence of haemophilus parasuis. Front Cell Infect Microbiol. 9:622019. View Article : Google Scholar : PubMed/NCBI
|
|
81
|
Xie LY, Xu YB, Ding XQ, Liang S, Li DL, Fu AK and Zhan XA: Itaconic acid and dimethyl itaconate exert antibacterial activity in carbon-enriched environments through the TCA cycle. Biomed Pharmacother. 167:1154872023. View Article : Google Scholar : PubMed/NCBI
|
|
82
|
Che C, Fan X, Wang H, Wang Z, Bao Y, Jiang W, Nawaz S, Yin H and Han X: 4-octyl itaconate modulates virulence-associated phenotypes and oxidative stress resistance in avian pathogenic Escherichia coli by targeting menB and wza. Poult Sci. Dec 6–2025.Epub ahead of print. PubMed/NCBI
|
|
83
|
Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, Korenfeld D, Mathyer ME, Kim H, Huang LH, et al: Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature. 556:501–504. 2018. View Article : Google Scholar : PubMed/NCBI
|
|
84
|
Yang C and Wang X: Lysosome biogenesis: Regulation and functions. J Cell Biol. 220:e2021020012021. View Article : Google Scholar : PubMed/NCBI
|
|
85
|
Zhang Z, Chen C, Yang F, Zeng YX, Sun P, Liu P and Li X: Itaconate is a lysosomal inducer that promotes antibacterial innate immunity. Mol Cell. 82:2844–2857.e10. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
86
|
Murphy MP: How mitochondria produce reactive oxygen species. Biochem J. 417:1–13. 2009. View Article : Google Scholar
|
|
87
|
O'Carroll SM, Peace CG, Toller-Kawahisa JE, Min Y, Hooftman A, Charki S, Kehoe L, O'Sullivan MJ, Zoller A, Mcgettrick AF, et al: Itaconate drives mtRNA-mediated type I interferon production through inhibition of succinate dehydrogenase. Nat Metab. 6:2060–2069. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
88
|
Luchkova A, Mata A and Cadenas S: Nrf2 as a regulator of energy metabolism and mitochondrial function. FEBS Lett. 598:2092–2105. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
89
|
Wu L, Hu Z, Luo X, Ge C, Lv Y, Zhan S, Huang W, Shen X, Yu D and Liu B: Itaconic acid alleviates perfluorooctanoic acid-induced oxidative stress and intestinal damage by regulating the keap1/Nrf2/Ho-1 pathway and reshaping the gut microbiota. Int J Mol Sci. 25:98262024. View Article : Google Scholar : PubMed/NCBI
|
|
90
|
Singh N and Bernstein CN: Environmental risk factors for inflammatory bowel disease. United European Gastroenterol J. 10:1047–1053. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
91
|
Pan X, Zhu Q, Pan LL and Sun J: Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy. Pharmacol Ther. 238:1081762022. View Article : Google Scholar : PubMed/NCBI
|
|
92
|
Chikina AS, Nadalin F, Maurin M, San-Roman M, Thomas-Bonafos T, Li XV, Lameiras S, Baulande S, Henri S, Malissen B, et al: Macrophages maintain epithelium integrity by limiting fungal product absorption. Cell. 183:411–428.e16. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
93
|
Castro-Dopico T, Fleming A, Dennison TW, Ferdinand JR, Harcourt K, Stewart BJ, Cader Z, Tuong ZK, Jing C, Lok LSC, et al: GM-CSF calibrates macrophage defense and wound healing programs during intestinal infection and inflammation. Cell Rep. 32:1078572020. View Article : Google Scholar : PubMed/NCBI
|
|
94
|
Zhao X, Di Q, Liu H, Quan J, Ling J, Zhao Z, Xiao Y, Wu H, Wu Z, Song W, et al: MEF2C promotes M1 macrophage polarization and Th1 responses. Cell Mol Immunol. 19:540–553. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
95
|
Zhang JX, Hu YX, Liu Y, Chen ZZ, Zheng JT, Qu XT, Zhang Y, Tang WY, Huang SC and Liu CS: Xianglian pill alleviates ulcerative colitis by inhibiting M1 macrophage polarization via modulation of energy metabolite itaconate. Phytomedicine. 135:1561792024. View Article : Google Scholar : PubMed/NCBI
|
|
96
|
Kim HW, Yu AR, Lee JW, Yoon HS, Lee BS, Park HW, Lee SK, Lee YI, Whang J and Kim JS: Aconitate decarboxylase 1 deficiency exacerbates mouse colitis induced by dextran sodium sulfate. Int J Mol Sci. 23:43922022. View Article : Google Scholar :
|
|
97
|
Reagan-Shaw S, Nihal M and Ahmad N: Dose translation from animal to human studies revisited. FASEB J. 22:659–661. 2008. View Article : Google Scholar
|
|
98
|
Wang Y, Zhao X, Gao Y, Zhao C, Li J, Wang S, Xue B, Liu C and Ma X: 4-Octyl itaconate alleviates dextran sulfate sodium-induced ulcerative colitis in mice via activating the KEAP1-NRF2 pathway. Inflammopharmacology. 32:2555–2574. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
99
|
Wang HG, Zhang MN, Wen X and Yang XZ: Itaconate aggravates experimental colitis. Clin Res Hepatol Gastroenterol. 45:1016292021. View Article : Google Scholar : PubMed/NCBI
|
|
100
|
Swain A, Bambouskova M, Kim H, Andhey PS, Duncan D, Auclair K, Chubukov V, Simons DM, Roddy TP, Stewart KM and Artyomov MN: Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab. 2:594–602. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
101
|
Tang C, Tan S, Zhang Y, Dong L and Xu Y: Activation of Keap1-Nrf2 signaling by 4-octyl itaconate protects human umbilical vein endothelial cells from high glucose. Biochem Biophys Res Commun. 508:921–927. 2019. View Article : Google Scholar
|
|
102
|
Li R, Ma Y, Wu H, Zhang X, Ding N, Li Z, Hu X, Rao J, Zhou Y, Wang L, et al: 4-Octyl itaconate alleviates endothelial cell inflammation and barrier dysfunction in LPS-induced sepsis via modulating TLR4/MAPK/NF-κB signaling: 4-Octyl itaconate alleviates endothelial dysfunction. Mol Med. 31:2402025. View Article : Google Scholar
|
|
103
|
Guo H, Guo H, Xie Y, Chen Y, Lu C, Yang Z, Zhu Y, Ouyang Y, Zhang Y and Wang X: Mo3Se4 nanoparticle with ROS scavenging and multi-enzyme activity for the treatment of DSS-induced colitis in mice. Redox Biol. 56:1024412022. View Article : Google Scholar
|
|
104
|
Wu R, Liu J, Wang N, Zeng L, Yu C, Chen F, Wang H, Billiar TR, Jiang J, Tang D and Kang R: Aconitate decarboxylase 1 is a mediator of polymicrobial sepsis. Sci Transl Med. 14:eabo20282022. View Article : Google Scholar : PubMed/NCBI
|
|
105
|
Nugent SG, Kumar D, Rampton DS and Evans DF: Intestinal luminal pH in inflammatory bowel disease: Possible determinants and implications for therapy with aminosalicylates and other drugs. Gut. 48:571–577. 2001. View Article : Google Scholar : PubMed/NCBI
|
|
106
|
Brinck JE, Sinha AK, Laursen MF, Dragsted LO, Raes J, Uribe RV, Walter J, Roager HM and Licht TR: Intestinal pH: A major driver of human gut microbiota composition and metabolism. Nat Rev Gastroenterol Hepatol. 22:639–656. 2025. View Article : Google Scholar : PubMed/NCBI
|
|
107
|
Klimeck L, Heisser T, Hoffmeister M and Brenner H: Colorectal cancer: A health and economic problem. Best Pract Res Clin Gastroenterol. 66:1018392023. View Article : Google Scholar : PubMed/NCBI
|
|
108
|
Dekker E, Tanis PJ, Vleugels JLA, Kasi PM and Wallace MB: Colorectal cancer. Lancet. 394:1467–1480. 2019. View Article : Google Scholar : PubMed/NCBI
|
|
109
|
Baidoun F, Elshiwy K, Elkeraie Y, Merjaneh Z, Khoudari G, Sarmini MT, Gad M, Al-Husseini M and Saad A: Colorectal cancer epidemiology: Recent trends and impact on outcomes. Curr Drug Targets. 22:998–1009. 2021. View Article : Google Scholar
|
|
110
|
Lasry A, Zinger A and Ben-Neriah Y: Inflammatory networks underlying colorectal cancer. Nat Immunol. 17:230–240. 2016. View Article : Google Scholar : PubMed/NCBI
|
|
111
|
Wang H, Tian T and Zhang J: Tumor-associated macrophages (TAMs) in colorectal cancer (CRC): From mechanism to therapy and prognosis. Int J Mol Sci. 22:84702021. View Article : Google Scholar : PubMed/NCBI
|
|
112
|
Schmitt M and Greten FR: The inflammatory pathogenesis of colorectal cancer. Nat Rev Immunol. 21:653–667. 2021. View Article : Google Scholar : PubMed/NCBI
|
|
113
|
Liu Y, Sun Q, Zhang C, Ding M, Wang C, Zheng Q, Ma Z, Xu H, Zhou G, Wang X, et al: STING-IRG1 inhibits liver metastasis of colorectal cancer by regulating the polarization of tumor-associated macrophages. iScience. 26:1073762023. View Article : Google Scholar : PubMed/NCBI
|
|
114
|
Martina JA and Puertollano R: The IRG1/itaconate/TFEB axis: A new weapon in macrophage antibacterial defense. Mol Cell. 82:2732–2734. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
115
|
Zhou S, Peng J, Xiao L, Zhou C, Fang Y, Ou Q, Qin J, Liu M, Pan Z and Hou Z: TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability. Cell Death Dis. 12:4632021. View Article : Google Scholar : PubMed/NCBI
|
|
116
|
Payandeh Z, Pirpour Tazehkand A, Barati G, Pouremamali F, Kahroba H, Baradaran B and Samadi N: Role of Nrf2 and mitochondria in cancer stem cells; in carcinogenesis, tumor progression, and chemoresistance. Biochimie. 179:32–45. 2020. View Article : Google Scholar : PubMed/NCBI
|
|
117
|
Zheng Y, Chen Z, She C, Lin Y, Hong Y, Shi L, Zhang Y, Cao P and Xu X: Four-octyl itaconate activates Nrf2 cascade to protect osteoblasts from hydrogen peroxide-induced oxidative injury. Cell Death Dis. 11:7722020. View Article : Google Scholar : PubMed/NCBI
|
|
118
|
Yang W, Wang Y, Huang Y, Yu J, Wang T, Li C, Yang L, Zhang P, Shi L, Yin Y, et al: 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to promote cuproptosis in colorectal cancer. Biomed Pharmacother. 159:1143012023. View Article : Google Scholar : PubMed/NCBI
|
|
119
|
Patel SG, Karlitz JJ, Yen T, Lieu CH and Boland CR: The rising tide of early-onset colorectal cancer: A comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 7:262–274. 2022. View Article : Google Scholar : PubMed/NCBI
|
|
120
|
Scheurlen KM, Hallion J, Snook DL, MacLeod A, Beal RJ, Parks MA, Littlefield AB, Hiken E, Billeter AT, Bensen J, et al: Itaconate and obesity-related hormones promote tumor progression-new insights on metabolic dysfunction in early-onset colon cancer. Front Immunol. 16:15729852025. View Article : Google Scholar
|
|
121
|
Niño DF, Sodhi CP and Hackam DJ: Necrotizing enterocolitis: New insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 13:590–600. 2016. View Article : Google Scholar : PubMed/NCBI
|
|
122
|
Alsaied A, Islam N and Thalib L: Global incidence of necrotizing enterocolitis: A systematic review and meta-analysis. BMC Pediat. 20:3442020. View Article : Google Scholar
|
|
123
|
Neu J and Walker WA: Necrotizing enterocolitis. N Engl J Med. 364:255–264. 2011. View Article : Google Scholar : PubMed/NCBI
|
|
124
|
Neu J, Modi N and Caplan M: Necrotizing enterocolitis comes in different forms: Historical perspectives and defining the disease. Semin Fetal Neonatal Med. 23:370–373. 2018. View Article : Google Scholar : PubMed/NCBI
|
|
125
|
Apostolidi DM, Kapetanidi M, Vretou E, Sarantaki A, Lykeridou K, Karampas G, Diamanti A, Vlachou M, Pantelaki N, Deltsidou A, et al: Morbidity and mortality trends in preterm neonates at the limits of viability: Retrospective observations from one greek hospital. Life (Basel). 15:7082025.PubMed/NCBI
|
|
126
|
Hall NJ, Eaton S and Pierro A: Royal australasia of surgeons guest lecture. Necrotizing enterocolitis: Prevention, treatment, and outcome. J Pediatr Surg. 48:2359–2367. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
127
|
Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh MC, Hale EC, Newman NS, Schibler K, Carlo WA, et al: Neonatal outcomes of extremely preterm infants from the NICHD neonatal research network. Pediatrics. 126:443–456. 2010. View Article : Google Scholar : PubMed/NCBI
|
|
128
|
Cho SX, Rudloff I, Lao JC, Pang MA, Goldberg R, Bui CB, McLean CA, Stock M, Klassert TE, Slevogt H, et al: Characterization of the pathoimmunology of necrotizing enterocolitis reveals novel therapeutic opportunities. Nat Commun. 11:57942020. View Article : Google Scholar : PubMed/NCBI
|
|
129
|
Huangfu S, Lan C, Li S, Wang H, Yan C, Yang Y, Tian B, Mu Y, Zhao P, Tian Y, et al: Itaconate suppresses neonatal intestinal inflammation via metabolic reprogramming of M1 macrophage. Clin Transl Med. 15:e704192025. View Article : Google Scholar : PubMed/NCBI
|
|
130
|
Donskey CJ: The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens. Clin Infect Dis. 39:219–226. 2004. View Article : Google Scholar : PubMed/NCBI
|
|
131
|
Rougerie P, Miskolci V and Cox D: Generation of membrane structures during phagocytosis and chemotaxis of macrophages: Role and regulation of the actin cytoskeleton. Immunol Rev. 256:222–239. 2013. View Article : Google Scholar : PubMed/NCBI
|
|
132
|
O'Callaghan AA, Dempsey E, Iyer N, Stiegeler S, Mercurio K and Corr SC: Intestinal metabolites influence macrophage phagocytosis and clearance of bacterial infection. Front Cell Infect Microbiol. 11:6224912021. View Article : Google Scholar : PubMed/NCBI
|
|
133
|
Joerger RD: Salmonella enterica's 'choice': Itaconic acid degradation or bacteriocin immunity genes. Genes (Basel). 11:7972020. View Article : Google Scholar
|
|
134
|
Hopkins EGD, Roumeliotis TI, Mullineaux-Sanders C, Choudhary JS and Frankel G: Intestinal epithelial cells and the microbiome undergo swift reprogramming at the inception of colonic citrobacter rodentium infection. mBio. 10:e00062–19. 2019. View Article : Google Scholar : PubMed/NCBI
|
|
135
|
Zhang T, Hasegawa Y and Waldor MK: Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis. Nat Microbiol. 9:3376–3390. 2024. View Article : Google Scholar : PubMed/NCBI
|
|
136
|
ElAzzouny M, Tom CT, Evans CR, Olson LL, Tanga MJ, Gallagher KA, Martin BR and Burant CF: Dimethyl itaconate is not metabolized into itaconate intracellularly. J Biol Chem. 292:4766–4769. 2017. View Article : Google Scholar : PubMed/NCBI
|
|
137
|
Liao ST, Han C, Xu DQ, Fu XW, Wang JS and Kong LY: 4-Octyl itaconate inhibits aerobic glycolysis by targeting GAPDH to exert anti-inflammatory effects. Nat Commun. 10:50912019. View Article : Google Scholar : PubMed/NCBI
|
|
138
|
Xu S, Zhao JY, Ma JY, Cui XL, Lin JH, Sun SY, Liu SJ, Zhou GK, Zhang JT, Kang P and Liu T: Desensitization of TRPA1 by dimethyl itaconate attenuates acute and chronic pain in mice. Front Pharmacol. 16:16714612025. View Article : Google Scholar : PubMed/NCBI
|
|
139
|
Yin N, Zhang W, Wei R, Yang Q, He F, Guo L and Feng M: Liposome cocktail activator modulates hepatocytes and remodels the microenvironment to mitigate acute liver failure. Asian J Pharm Sci. 17:867–879. 2022.
|
|
140
|
Rezazadeh Ardabili A, Van Esser D, Wintjens D, Cilissen M, Deben D, Mujagic Z, Russ F, Stassen L, Van Bodegraven A, Wong D, et al: The risk of mild, moderate, and severe infections in IBD patients-A prospective, multicentre observational cohort study (PRIQ). J Crohns Colitis. Jul 9–2025.Epub ahead of print. View Article : Google Scholar
|
|
141
|
Ryan DG and O'Neill LAJ: Krebs cycle rewired for macrophage and dendritic cell effector functions. FEBS Lett. 591:2992–3006. 2017. View Article : Google Scholar : PubMed/NCBI
|
|
142
|
Sohail A, Iqbal AA, Sahini N, Chen F, Tantawy M, Waqas SFH, Winterhoff M, Ebensen T, Schultz K, Geffers R, et al: Itaconate and derivatives reduce interferon responses and inflammation in influenza A virus infection. PLoS Pathog. 18:e10102192022. View Article : Google Scholar : PubMed/NCBI
|
|
143
|
Yang Z, Zhang L, Ottavi S, Geri JB, Perkowski A, Jiang X, Pfau D, Bryk R, Aubé J, Zimmerman M, et al: ACOD1-mediated lysosomal membrane permeabilization contributes to Mycobacterium tuberculosis-induced macrophage death. Proc Natl Acad Sci USA. 122:e24253091222025. View Article : Google Scholar : PubMed/NCBI
|
|
144
|
Kang M, Tang D, Huang W, Zhou M, Ma Q, Lan Y, Chen D, Li Y and Han B: Emerging role of Itaconate in inflammatory bowel disease: From multitarget Immunometabolic mechanisms to therapeutic translation. Int Immunopharmacol. 166:1156322025. View Article : Google Scholar : PubMed/NCBI
|
|
145
|
Weiss JM, Palmieri EM, Gonzalez-Cotto M, Bettencourt IA, Megill EL, Snyder NW and McVicar DW: Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice. Nat Metab. 5:981–995. 2023. View Article : Google Scholar : PubMed/NCBI
|
|
146
|
Zhang X, Zhi Y, Zan X, Fan K, Chen K, Zhao S, Dai X, Li L, Yang Y, Hu K, et al: Immune response gene 1 deficiency aggravates high fat diet-induced nonalcoholic fatty liver disease via promotion of redox-sensitive AKT suppression. Biochim Biophys Acta Mol Basis Dis. 1869:1666562023. View Article : Google Scholar : PubMed/NCBI
|
