Macrophage plasticity: signaling pathways, tissue repair, and regeneration

Abstract

Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt to diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) and alternatively activated (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay of signaling pathways, transcriptional regulators, and epigenetic modifications orchestrates macrophage polarization, allowing them to respond to various stimuli dynamically. Here, we provide a comprehensive overview of the signaling cascades governing macrophage plasticity, focusing on the roles of Toll-like receptors, signal transducer and activator of transcription proteins, nuclear receptors, and microRNAs. We also discuss the emerging concepts of macrophage metabolic reprogramming and trained immunity, contributing to their functional adaptability. Macrophage plasticity plays a pivotal role in tissue repair and regeneration, with macrophages coordinating inflammation, angiogenesis, and matrix remodeling to restore tissue homeostasis. By harnessing the potential of macrophage plasticity, novel therapeutic strategies targeting macrophage polarization could be developed for various diseases, including chronic wounds, fibrotic disorders, and inflammatory conditions. Ultimately, a deeper understanding of the molecular mechanisms underpinning macrophage plasticity will pave the way for innovative regenerative medicine and tissue engineering approaches.

Keywords

epigenetic regulation / macrophages / plasticity / signaling pathways / tissue repair

References

[1] Raziyeva K, Kim Y, Zharkinbekov Z, Kassymbek K, Jimi S, Saparov A. Immunology of acute and chronic wound healing. Biomolecules. 2021; 11(5): 700.

[2] Hassanshahi A, Moradzad M, Ghalamkari S, Fadaei M, Cowin AJ, Hassanshahi M. Macrophage-mediated inflammation in skin wound healing. Cells. 2022; 11(19): 2953.

[3] Kloc M, Ghobrial RM, Wosik J, Lewicka A, Lewicki S, Kubiak JZ. Macrophage functions in wound healing. J Tissue Eng Regen Med. 2019; 13(1): 99-109.

[4] Chen C, Liu T, Tang Y, Luo G, Liang G, He W. Epigenetic regulation of macrophage polarization in wound healing. Burns Trauma. 2023; 11: tkac057.

[5] Viola A, Munari F, Sánchez-Rodríguez R, Scolaro T, Castegna A. The metabolic signature of macrophage responses. Front Immunol. 2019; 10: 1462.

[6] Sun X, Li Y, Deng Q, et al. Macrophage polarization, metabolic reprogramming, and inflammatory effects in ischemic heart disease. Front Immunol. 2022; 13: 934040.

[7] Willenborg S, Sanin DE, Jais A, et al. Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing. Cell Metab. 2021; 33(12): 2398-2414. e9.

[8] Theocharidis G, Thomas BE, Sarkar D, et al. Single cell transcriptomic landscape of diabetic foot ulcers. Nat Commun. 2022; 13(1): 181.

[9] Funes SC, Rios M, Escobar-Vera J, Kalergis AM. Implications of macrophage polarization in autoimmunity. Immunology. 2018; 154(2): 186-195.

[10] Mantovani A, Sica A, Locati M. Macrophage polarization comes of age. Immunity. 2005; 23(4): 344-346.

[11] Karlinsey K, Qu L, Matz AJ, Zhou B. A novel strategy to dissect multifaceted macrophage function in human diseases. J Leukoc Biol. 2022; 112(6): 1535-1542.

[12] An L, Michaeli J, Pallavi P, et al. Concurrent stimulation of monocytes with CSF1 and polarizing cytokines reveals phenotypic and functional differences with classical polarized macrophages. J Leukoc Biol. 2022; 112(3): 437-447.

[13] O’Brien EM, Spiller KL. Pro-inflammatory polarization primes Macrophages to transition into a distinct M2-like phenotype in response to IL-4. J Leukoc Biol. 2022; 111(5): 989-1000.

[14] Liang B, Wang H, Wu D, Wang Z. Macrophage M1/M2 polarization dynamically adapts to changes in microenvironment and modulates alveolar bone remodeling after dental implantation. J Leukoc Biol. 2021; 110(3): 433-447.

[15] Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol. 2000; 164(12): 6166-6173.

[16] Eming SA, Murray PJ, Pearce EJ. Metabolic orchestration of the wound healing response. Cell Metab. 2021; 33(9): 1726-1743.

[17] He P, Dai M, Li Z, et al. Effect of connexin 43 in LPS/IL-4-induced macrophage M1/M2 polarization: an observational study. Medicine (Baltimore). 2024; 103(15): e37811.

[18] Scott TE, Lewis CV, Zhu M, et al. IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages. Sci Rep. 2023; 13(1): 19589.

[19] Zhu Y, Chen X, Lu Y, et al. Glutamine mitigates murine burn sepsis by supporting macrophage M2 polarization through repressing the SIRT5-mediated desuccinylation of pyruvate dehydrogenase. Burns Trauma. 2022; 10: tkac041.

[20] Strizova Z, Benesova I, Bartolini R, et al. M1/M2 macrophages and their overlaps - myth or reality? Clin Sci (Lond). 2023; 137(15): 1067-1093.

[21] Oliver MA, Davis XD, Bohannon JK. TGFβ macrophage reprogramming: a new dimension of macrophage plasticity. J Leukoc Biol. 2024; 115(3): 411-414.

[22] Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016; 44(3): 450-462.

[23] Xia T, Fu S, Yang R, et al. Advances in the study of macrophage polarization in inflammatory immune skin diseases. J Inflamm (Lond). 2023; 20(1): 33.

[24] Gordon S. Phagocytosis: the legacy of Metchnikoff. Cell. 2016; 166(5): 1065-1068.

[25] Life of Elie Metchnikoff, 1845–1916. Nature. 1922; 109(2728): 163-166.

[26] Van Epps HL. Macrophage activation unveiled. J Exp Med. 2005; 202(7): 884.

[27] Palmieri EM, McGinity C, Wink DA, McVicar DW. Nitric oxide in macrophage immunometabolism: hiding in plain sight. Metabolites. 2020; 10(11): 429.

[28] Wlaschek M, Singh K, Sindrilaru A, Crisan D, Scharffetter-Kochanek K. Iron and iron-dependent reactive oxygen species in the regulation of macrophages and fibroblasts in non-healing chronic wounds. Free Radic Biol Med. 2019; 133: 262-275.

[29] Liu L, Guo H, Song A, et al. Progranulin inhibits LPS-induced macrophage M1 polarization via NF-кB and MAPK pathways. BMC Immunol. 2020; 21(1): 32.

[30] Kashfi K, Kannikal J, Nath N. Macrophage reprogramming and cancer therapeutics: role of iNOS-derived NO. Cells. 2021; 10(11): 3194.

[31] Mackaness GB, Blanden RV. Cellular immunity. Prog Allergy. 1967; 11: 89-140.

[32] Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992; 176(1): 287-292.

[33] von Recklinghausen F. Ueber Eiter-und Bindegewebskörperchen. Arch Pathol Anat Physiol Klin Med. 1863; 28(1): 157-197.

[34] Tauber AI. Metchnikoff and the phagocytosis theory. Nat Rev Mol Cell Biol. 2003; 4(11): 897-901.

[35] Sródka A, Gryglewski RW, Szczepariski W. Browicz or Kupffer cells? Pol J Pathol. 2006; 57(4): 183-185.

[36] Aschoff L. Das reticuloendotheliale System. Ergebn Inn Med Kinderheilk. 1924; 26: 1-118.

[37] van Furth R, Cohn ZA. The origin and kinetics of mononuclear phagocytes. J Exp Med. 1968; 128(3): 415-435.

[38] van Furth R. Current view on the mononuclear phagocyte system. Immunobiology. 1982; 161(3-4): 178-185.

[39] Quintin J, Saeed S, Martens JHA, et al. Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes. Cell Host Microbe. 2012; 12(2): 223-232.

[40] Lavin Y, Winter D, Blecher-Gonen R, et al. Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment. Cell. 2014; 159(6): 1312-1326.

[41] Xue J, Schmidt SV, Sander J, et al. Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity. 2014; 40(2): 274-288.

[42] Cheng SC, Quintin J, Cramer RA, et al. mTOR-and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science. 2014; 345(6204): 1250684.

[43] Arts RJ, Novakovic B, Ter Horst R, et al. Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity. Cell Metab. 2016; 24(6): 807-819.

[44] Roussel M, Ferrell PB, Jr., Greenplate AR, et al. Mass cytometry deep phenotyping of human mononuclear phagocytes and myeloid-derived suppressor cells from human blood and bone marrow. J Leukoc Biol. 2017; 102(2): 437-447.

[45] Zilionis R, Engblom C, Pfirschke C, et al. Single-cell transcriptomics of human and mouse lung cancers reveals conserved myeloid populations across individuals and species. Immunity. 2019; 50(5): 1317-1334. e10.

[46] Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front Immunol. 2019; 10: 1084.

[47] Wu MM, Wang QM, Huang BY, et al. Dioscin ameliorates murine ulcerative colitis by regulating macrophage polarization. Pharmacol Res. 2021; 172: 105796.

[48] Lin YH, Wang YH, Peng YJ, et al. Interleukin 26 skews macrophage polarization towards M1 phenotype by activating cJUN and the NF-κB pathway. Cells. 2020; 9(4): 938.

[49] Liu L, Stokes JV, Tan W, Pruett SB. An optimized flow cytometry panel for classifying macrophage polarization. J Immunol Methods. 2022; 511: 113378.

[50] Zhang J, Liu X, Wan C, et al. NLRP3 inflammasome mediates M1 macrophage polarization and IL-1β production in inflammatory root resorption. J Clin Periodontol. 2020; 47(4): 451-460.

[51] Hirani D, Alvira CM, Danopoulos S, et al. Macrophage-derived IL-6 trans-signalling as a novel target in the pathogenesis of bronchopulmonary dysplasia. Eur Respir J. 2022; 59(2): 2002248.

[52] Cutolo M, Campitiello R, Gotelli E, Soldano S. The role of M1/M2 macrophage polarization in rheumatoid arthritis synovitis. Front Immunol. 2022; 13: 867260.

[53] Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018; 233(9): 6425-6440.

[54] Zhang B, Yang Y, Yi J, Zhao Z, Ye R. Hyperglycemia modulates M1/M2 macrophage polarization via reactive oxygen species overproduction in ligature-induced periodontitis. J Periodontal Res. 2021; 56(5): 991-1005.

[55] Rendra E, Riabov V, Mossel DM, Sevastyanova T, Harmsen MC, Kzhyshkowska J. Reactive oxygen species (ROS) in macrophage activation and function in diabetes. Immunobiology. 2019; 224(2): 242-253.

[56] Fan X, Zheng S, Chen C, et al. Sialidase facilitates Porphyromonas gingivalis immune evasion by reducing M1 polarization, antigen presentation, and phagocytosis of infected macrophages. Front Cell Infect Microbiol. 2023; 13: 1173899.

[57] Mohammadi A, Blesso CN, Barreto GE, Banach M, Majeed M, Sahebkar A. Macrophage plasticity, polarization and function in response to curcumin, a diet-derived polyphenol, as an immunomodulatory agent. J Nutr Biochem. 2019; 66: 1-16.

[58] Bogen B, Fauskanger M, Haabeth OA, Tveita A. CD4(+) T cells indirectly kill tumor cells via induction of cytotoxic macrophages in mouse models. Cancer Immunol Immunother. 2019; 68(11): 1865-1873.

[59] Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage. 2020; 28(5): 555-561.

[60] Ma PF, Gao CC, Yi J, et al. Cytotherapy with M1-polarized macrophages ameliorates liver fibrosis by modulating immune microenvironment in mice. J Hepatol. 2017; 67(4): 770-779.

[61] Ishikawa S, Noma T, Fu HY, et al. Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice. PLoS One. 2017; 12(11): e0187894.

[62] Louiselle AE, Niemiec SM, Zgheib C, Liechty KW. Macrophage polarization and diabetic wound healing. Transl Res. 2021; 236: 109-116.

[63] Sharifiaghdam M, Shaabani E, Faridi-Majidi R, De Smedt SC, Braeckmans K, Fraire JC. Macrophages as a therapeutic target to promote diabetic wound healing. Mol Ther. 2022; 30(9): 2891-2908.

[64] Gao X, Lu C, Miao Y, Ren J, Cai X. Role of macrophage polarisation in skin wound healing. Int Wound J. 2023; 20(7): 2551-2562.

[65] He Y, Gao Y, Zhang Q, Zhou G, Cao F, Yao S. IL-4 switches microglia/macrophage M1/M2 polarization and alleviates neurological damage by modulating the JAK1/STAT6 pathway following ICH. Neuroscience. 2020; 437: 161-171.

[66] Gao S, Zhou J, Liu N, et al. Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13. J Mol Cell Cardiol. 2015; 85: 131-139.

[67] Lundahl MLE, Mitermite M, Ryan DG, et al. Macrophage innate training induced by IL-4 and IL-13 activation enhances OXPHOS driven anti-mycobacterial responses. Elife. 2022; 11: e74690.

[68] Huang X, Li Y, Fu M, Xin HB. Polarizing Macrophages In Vitro. Methods Mol Biol. 2018; 1784: 119-126.

[69] Qu R, Zhou M, Qiu Y, et al. Glucocorticoids improve the balance of M1/M2 macrophage polarization in experimental autoimmune uveitis through the P38MAPK-MEF2C axis. Int Immunopharmacol. 2023; 120: 110392.

[70] Luo L, Wang S, Hu Y, et al. Precisely Regulating M2 Subtype Macrophages for Renal Fibrosis Resolution. ACS Nano. 2023; 17(22): 22508-22526.

[71] Chen S, Wang M, Lu T, et al. JMJD6 in tumor-associated macrophage regulates macrophage polarization and cancer progression via STAT3/IL-10 axis. Oncogene. 2023; 42(37): 2737-2750.

[72] Wang L, He C. Nrf2-mediated anti-inflammatory polarization of macrophages as therapeutic targets for osteoarthritis. Front Immunol. 2022; 13: 967193.

[73] Kiseleva V, Vishnyakova P, Elchaninov A, Fatkhudinov T, Sukhikh G. Biochemical and molecular inducers and modulators of M2 macrophage polarization in clinical perspective. Int Immunopharmacol. 2023; 122: 110583.

[74] Fang J, Ou Q, Wu B, et al. TcpC inhibits M1 but promotes M2 macrophage polarization via regulation of the MAPK/NF-κB and Akt/STAT6 pathways in urinary tract infection. Cells. 2022; 11(17): 2674.

[75] Wang J, Xu L, Xiang Z, et al. Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206(+) M2-like macrophage polarization. Cell Death Dis. 2020; 11(2): 136.

[76] Xu ZJ, Gu Y, Wang CZ, et al. The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia. Oncoimmunology. 2020; 9(1): 1683347.

[77] Zhu Y, Sun X, Tan S, et al. M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps. Front Immunol. 2022; 13: 1047930.

[78] Mahon OR, Browe DC, Gonzalez-Fernandez T, et al. Nano-particle mediated M2 macrophage polarization enhances bone formation and MSC osteogenesis in an IL-10 dependent manner. Biomaterials. 2020; 239: 119833.

[79] Chen X, Wan Z, Yang L, et al. Exosomes derived from reparative M2-like macrophages prevent bone loss in murine periodontitis models via IL-10 mRNA. J Nanobiotechnology. 2022; 20(1): 110.

[80] Hu J, Deng F, Zhao B, et al. Lactobacillus murinus alleviate intestinal ischemia/reperfusion injury through promoting the release of interleukin-10 from M2 macrophages via Toll-like receptor 2 signaling. Microbiome. 2022; 10(1): 38.

[81] Fu XH, Li JP, Li XY, et al. M2-macrophage-derived exosomes promote meningioma progression through TGF-β signaling pathway. J Immunol Res. 2022; 2022: 8326591.

[82] Cai G, Lu Y, Zhong W, et al. Piezo1-mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor-β1. Cell Prolif. 2023; 56(9): e13440.

[83] Nakazaki M, Morita T, Lankford KL, Askenase PW, Kocsis JD. Small extracellular vesicles released by infused mesenchymal stromal cells target M2 macrophages and promote TGF-β upregulation, microvascular stabilization and functional recovery in a rodent model of severe spinal cord injury. J Extracell Vesicles. 2021; 10(11): e12137.

[84] Oh S, Lee JH, Kim HM, et al. Poly-L-lactic acid fillers improved dermal collagen synthesis by modulating M2 macrophage polarization in aged animal skin. Cells. 2023; 12(9): 1320.

[85] Li S, Ding X, Zhang H, Ding Y, Tan Q. IL-25 improves diabetic wound healing through stimulating M2 macrophage polarization and fibroblast activation. Int Immunopharmacol. 2022; 106: 108605.

[86] Wang Y, Geng X, Guo Z, et al. M2 macrophages promote subconjunctival fibrosis through YAP/TAZ signalling. Ann Med. 2024; 56(1): 2313680.

[87] Zhang J, Muri J, Fitzgerald G, et al. Endothelial lactate controls muscle regeneration from ischemia by inducing M2-like macrophage polarization. Cell Metab. 2020; 31(6): 1136-1153. e7.

[88] Lu Y, Han G, Zhang Y, et al. M2 macrophage-secreted exosomes promote metastasis and increase vascular permeability in hepatocellular carcinoma. Cell Commun Signal. 2023; 21(1): 299.

[89] Xu H, Zhu Y, Hsiao AW, et al. Bioactive glass-elicited stem cell-derived extracellular vesicles regulate M2 macrophage polarization and angiogenesis to improve tendon regeneration and functional recovery. Biomaterials. 2023; 294: 121998.

[90] Razi S, Yaghmoorian Khojini J, Kargarijam F, et al. Macrophage efferocytosis in health and disease. Cell Biochem Funct. 2023; 41(2): 152-165.

[91] Aitcheson SM, Frentiu FD, Hurn SE, Edwards K, Murray RZ. Skin wound healing: normal macrophage function and macrophage dysfunction in diabetic wounds. Molecules. 2021; 26(16): 4917.

[92] Zhong X, Lee HN, Kim SH, et al. Myc-nick promotes efferocytosis through M2 macrophage polarization during resolution of inflammation. Faseb J. 2018; 32(10): 5312-5325.

[93] Govindappa PK, Elfar JC. Erythropoietin promotes M2 macrophage phagocytosis of Schwann cells in peripheral nerve injury. Cell Death Dis. 2022; 13(3): 245.

[94] Ying W, Gao H, Dos Reis FCG, et al. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab. 2021; 33(4): 781-790. e5.

[95] Li X, Ren Y, Chang K, et al. Adipose tissue macrophages as potential targets for obesity and metabolic diseases. Front Immunol. 2023; 14: 1153915.

[96] Russo S, Kwiatkowski M, Govorukhina N, Bischoff R, Melgert BN. Meta-inflammation and metabolic reprogramming of macrophages in diabetes and obesity: the importance of metabolites. Front Immunol. 2021; 12: 746151.

[97] Savitri C, Kwon JW, Drobyshava V, Ha SS, Park K. M2 macrophage-derived concentrated conditioned media significantly improves skin wound healing. Tissue Eng Regen Med. 2022; 19(3): 617-628.

[98] Pi L, Fang B, Meng X, Qian L. LncRNA XIST accelerates burn wound healing by promoting M2 macrophage polarization through targeting IL-33 via miR-19b. Cell Death Discov. 2022; 8(1): 220.

[99] Li S, Yang P, Ding X, Zhang H, Ding Y, Tan Q. Puerarin improves diabetic wound healing via regulation of macrophage M2 polarization phenotype. Burns Trauma. 2022; 10: tkac046.

[100] Anders CB, Lawton TMW, Ammons MCB. Metabolic immunomodulation of macrophage functional plasticity in nonhealing wounds. Curr Opin Infect Dis. 2019; 32(3): 204-209.

[101] Hourani T, Perez-Gonzalez A, Khoshmanesh K, et al. Label-free macrophage phenotype classification using machine learning methods. Sci Rep. 2023; 13(1): 5202.

[102] Ordaz-Arias MA, Díaz-Alvarez L, Zúñiga J, Martinez-Sánchez ME, Balderas-Martínez YI. Cyclic attractors are critical for macrophage differentiation, heterogeneity, and plasticity. Front Mol Biosci. 2022; 9: 807228.

[103] Zhang Q, Sioud M. Tumor-associated macrophage subsets: shaping polarization and targeting. Int J Mol Sci. 2023; 24(8): 7493.

[104] Nakai K. Multiple roles of macrophage in skin. J Dermatol Sci. 2021; 104(1): 2-10.

[105] Anders CB, Lawton TMW, Smith HL, Garret J, Doucette MM, Ammons MCB. Use of integrated metabolomics, transcriptomics, and signal protein profile to characterize the effector function and associated metabotype of polarized macrophage phenotypes. J Leukoc Biol. 2022; 111(3): 667-693.

[106] Kang H, Bang JY, Mo Y, et al. Effect of Acinetobacter lwoffii on the modulation of macrophage activation and asthmatic inflammation. Clin Exp Allergy. 2022; 52(4): 518-529.

[107] Kuo CH, Tsai ML, Li CH, et al. Altered pattern of macrophage polarization as a biomarker for severity of childhood asthma. J Inflamm Res. 2021; 14: 6011-6023.

[108] Feng D, Huang WY, Niu XL, Hao S, Zhang LN, Hu YJ. Significance of macrophage subtypes in the peripheral blood of children with systemic juvenile idiopathic arthritis. Rheumatol Ther. 2021; 8(4): 1859-1870.

[109] Fan P, Zhang Y, Ding S, Du Z, Zhou C, Du X. Integrating RNA-seq and scRNA-seq to explore the mechanism of macrophage ferroptosis associated with COPD. Front Pharmacol. 2023; 14: 1139137.

[110] Barreby E, Chen P, Aouadi M. Macrophage functional diversity in NAFLD - more than inflammation. Nat Rev Endocrinol. 2022; 18(8): 461-472.

[111] Masuda T, Sankowski R, Staszewski O, Prinz M. Microglia heterogeneity in the single-cell era. Cell Rep. 2020; 30(5): 1271-1281.

[112] Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016; 19(8): 987-991.

[113] Angel CE, Chen CJJ, Horlacher OC, et al. Distinctive localization of antigen-presenting cells in human lymph nodes. Immunobiology. 2009; 113(6): 1257-1267.

[114] Aegerter H, Lambrecht BN, Jakubzick CV. Biology of lung macrophages in health and disease. Immunity. 2022; 55(9): 1564-1580.

[115] Yao C, Cao Y, Wang D, et al. Single-cell sequencing reveals microglia induced angiogenesis by specific subsets of endothelial cells following spinal cord injury. Faseb J. 2022; 36(7): e22393.

[116] Yue Z, Nie L, Zhang P, Chen Q, Lv Q, Wang Q. Tissue-resident macrophage inflammaging aggravates homeostasis dysregulation in age-related diseases. Cell Immunol. 2021; 361: 104278.

[117] Gosselin D, Link VM, Romanoski CE, et al. Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell. 2014; 159(6): 1327-1340.

[118] Blériot C, Chakarov S, Ginhoux F. Determinants of resident tissue macrophage identity and function. Immunity. 2020; 52(6): 957-970.

[119] Delfini M, Stakenborg N, Viola MF, Boeckxstaens G. Macrophages in the gut: masters in multitasking. Immunity. 2022; 55(9): 1530-1548.

[120] Gabanyi I, Muller PA, Feighery L, Oliveira TY, Costa-Pinto FA, Mucida D. Neuro-immune interactions drive tissue programming in intestinal macrophages. Cell. 2016; 164(3): 378-391.

[121] Schulthess J, Pandey S, Capitani M, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity. 2019; 50(2): 432-445. e7.

[122] Duan H, Wang L, Huangfu M, Li H. The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: mechanisms and therapeutic potentials. Biomed Pharmacother. 2023; 165: 115276.

[123] Meng L, Lu C, Wu B, et al. Taurine antagonizes macrophages M1 polarization by mitophagy-glycolysis switch blockage via dragging SAM-PP2Ac transmethylation. Front Immunol. 2021; 12: 648913.

[124] Jia D, Chen S, Bai P, et al. Cardiac resident macrophage-derived legumain improves cardiac repair by promoting clearance and degradation of apoptotic cardiomyocytes after myocardial infarction. Circulation. 2022; 145(20): 1542-1556.

[125] Hill DA, Lim HW, Kim YH, et al. Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue. Proc Natl Acad Sci USA. 2018; 115(22): E5096-E5105.

[126] Lazarov T, Juarez-Carreño S, Cox N, Geissmann F. Physiology and diseases of tissue-resident macrophages. Nature. 2023; 618(7966): 698-707.

[127] Wu Y, Hirschi KK. Tissue-resident macrophage development and function. Front Cell Dev Biol. 2020; 8: 617879.

[128] Yona S, Kim KW, Wolf Y, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity. 2013; 38(1): 79-91.

[129] Xu Y, Schrank PR, Williams JW. Macrophage fate mapping. Curr Protoc. 2022; 2(6): e456.

[130] Prinz M, Masuda T, Wheeler MA, Quintana FJ. Microglia and central nervous system-associated macrophages-from origin to disease modulation. Annu Rev Immunol. 2021; 39: 251-277.

[131] Fan X, Lu P, Cui XH, et al. Repopulating Kupffer cells originate directly from hematopoietic stem cells. Stem Cell Res Ther. 2023; 14(1): 351.

[132] Dick SA, Wong A, Hamidzada H, et al. Three tissue resident macrophage subsets coexist across organs with conserved origins and life cycles. Sci Immunol. 2022; 7(67): eabf7777.

[133] Richoz N, Tuong ZK, Loudon KW, et al. Distinct pathogenic roles for resident and monocyte-derived macrophages in lupus nephritis. JCI Insight. 2022; 7(21): e159751.

[134] Rizzo G, Gropper J, Piollet M, et al. Dynamics of monocyte-derived macrophage diversity in experimental myocardial infarction. Cardiovasc Res. 2023; 119(3): 772-785.

[135] Kloc M, Kubiak JZ. Monocyte and macrophage function diversity. Int J Mol Sci. 2022; 23(20): 12404.

[136] Ochando J, Mulder WJM, Madsen JC, Netea MG, Duivenvoorden R. Trained immunity - basic concepts and contributions to immunopathology. Nat Rev Nephrol. 2023; 19(1): 23-37.

[137] Guo Z, Wang L, Liu H, Xie Y. Innate immune memory in monocytes and macrophages: the potential therapeutic strategies for atherosclerosis. Cells. 2022; 11(24): 4072.

[138] Ferluga J, Yasmin H, Al-Ahdal MN, Bhakta S, Kishore U. Natural and trained innate immunity against Mycobacterium tuberculosis. Immunobiology. 2020; 225(3): 151951.

[139] Jeyanathan M, Vaseghi-Shanjani M, Afkhami S, et al. Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut-lung axis. Nat Immunol. 2022; 23(12): 1687-1702.

[140] Arts RJ, Blok BA, van Crevel R, et al. Vitamin A induces inhibitory histone methylation modifications and down-regulates trained immunity in human monocytes. J Leukoc Biol. 2015; 98(1): 129-136.

[141] Adams K, Weber KS, Johnson SM. Exposome and immunity training: how pathogen exposure order influences innate immune cell lineage commitment and function. Int J Mol Sci. 2020; 21(22): 8462.

[142] Chen J, Gao L, Wu X, et al. BCG-induced trained immunity: history, mechanisms and potential applications. J Transl Med. 2023; 21(1): 106.

[143] Mora VP, Loaiza RA, Soto JA, Bohmwald K, Kalergis AM. Involvement of trained immunity during autoimmune responses. J Autoimmun. 2023; 137: 102956.

[144] Fani Maleki A, Cisbani G, Plante MM, et al. Muramyl dipeptide-mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer’s disease. J Neuroinflammation. 2020; 17(1): 218.

[145] Moorlag S, Rodriguez-Rosales YA, Gillard J, et al. BCG vaccination induces long-term functional reprogramming of human neutrophils. Cell Rep. 2020; 33(7): 108387.

[146] Vázquez-Carballo C, Guerrero-Hue M, García-Caballero C, et al. Toll-like receptors in acute kidney injury. Int J Mol Sci. 2021; 22(2): 816.

[147] Duan T, Du Y, Xing C, Wang HY, Wang RF. Toll-like receptor signaling and its role in cell-mediated immunity. Front Immunol. 2022; 13: 812774.

[148] Onyishi CU, Desanti GE, Wilkinson AL, et al. Toll-like receptor 4 and macrophage scavenger receptor 1 crosstalk regulates phagocytosis of a fungal pathogen. Nat Commun. 2023; 14(1): 4895.

[149] Kirchner S, Lei V, MacLeod AS. The cutaneous wound innate immunological microenvironment. Int J Mol Sci. 2020; 21(22): 8748.

[150] Wang L, Wang J, Han L, Chen T. Palmatine attenuated lipopolysaccharide-induced acute lung injury by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling. J Agric Food Chem. 2024.

[151] Owen AM, Luan L, Burelbach KR, et al. MyD88-dependent signaling drives toll-like receptor-induced trained immunity in macrophages. Front Immunol. 2022; 13: 1044662.

[152] Hsieh WY, Zhou QD, York AG, et al. Toll-like receptors induce signal-specific reprogramming of the macrophage lipidome. Cell Metab. 2020; 32(1): 128-143. e5.

[153] Yamamoto M, Sato S, Hemmi H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003; 301(5633): 640-643.

[154] Pereira M, Durso DF, Bryant CE, et al. The IRAK4 scaffold integrates TLR4-driven TRIF and MYD88 signaling pathways. Cell Rep. 2022; 40(7): 111225.

[155] Luo X, Bao X, Weng X, et al. The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway. Life Sci. 2022; 291: 120064.

[156] Li Y, Zhang L, Ren P, et al. Qing-Xue-Xiao-Zhi formula attenuates atherosclerosis by inhibiting macrophage lipid accumulation and inflammatory response via TLR4/MyD88/NF-κB pathway regulation. Phytomedicine. 2021; 93: 153812.

[157] McKiel LA, Woodhouse KA, Fitzpatrick LE. A macrophage reporter cell assay to examine toll-like receptor-mediated NF-kB/AP-1 signaling on adsorbed protein layers on polymeric surfaces. J Vis Exp. 2020;(155):

[158] Hannemann N, Cao S, Eriksson D, et al. Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis. J Clin Invest. 2019; 129(7): 2669-2684.

[159] Negishi H, Ohba Y, Yanai H, et al. Negative regulation of Toll-like-receptor signaling by IRF-4. Proc Natl Acad Sci USA. 2005; 102(44): 15989-15994.

[160] Wu L, Chen L, Li H, et al. Nocardia rubra cell-wall skeleton mitigates whole abdominal irradiation-induced intestinal injury via regulating macrophage function. Burns Trauma. 2024; 12: tkad045.

[161] Olona A, Hateley C, Muralidharan S, Wenk MR, Torta F, Behmoaras J. Sphingolipid metabolism during Toll-like receptor 4 (TLR4)-mediated macrophage activation. Br J Pharmacol. 2021; 178(23): 4575-4587.

[162] Ye Y, Wang Y, Yang Y, Tao L. Aloperine suppresses LPS-induced macrophage activation through inhibiting the TLR4/NF-κB pathway. Inflamm Res. 2020; 69(4): 375-383.

[163] Zhang Y, Song Y, Du J, et al. S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion. Burns Trauma. 2023; 11: tkad030.

[164] Xie XD, Tang M, Yi SL, et al. Polysaccharide of Asparagus cochinchinensis (Lour.) Merr regulates macrophage immune response and epigenetic memory through TLR4-JNK/p38/ERK signaling pathway and histone modification. Phytomedicine. 2024; 124: 155294.

[165] Bode JG, Ehlting C, Häussinger D. The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis. Cell Signal. 2012; 24(6): 1185-1194.

[166] Hu J, Wang H, Li X, et al. Fibrinogen-like protein 2 aggravates nonalcoholic steatohepatitis via interaction with TLR4, eliciting inflammation in macrophages and inducing hepatic lipid metabolism disorder. Theranostics. 2020; 10(21): 9702-9720.

[167] Xiao J, Li W, Zheng X, et al. Targeting 7-dehydrocholesterol reductase integrates cholesterol metabolism and IRF3 activation to eliminate infection. Immunity. 2020; 52(1): 109-122. e6.

[168] Seebach E, Sonnenmoser G, Kubatzky KF. Staphylococcus aureus planktonic but not biofilm environment induces an IFN-β macrophage immune response via the STING/IRF3 pathway. Virulence. 2023; 14(1): 2254599.

[169] Zhang C, Cheng N, Qiao B, et al. Age-related decline of interferon-gamma responses in macrophage impairs satellite cell proliferation and regeneration. J Cachexia Sarcopenia Muscle. 2020; 11(5): 1291-1305.

[170] Zheng M, Karki R, Williams EP, et al. TLR2 senses the SARS-CoV-2 envelope protein to produce inflammatory cytokines. Nat Immunol. 2021; 22(7): 829-838.

[171] Khan S, Shafiei MS, Longoria C, Schoggins JW, Savani RC, Zaki H. SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. Elife. 2021; 10: e68563.

[172] Qian Y, Chu G, Zhang L, et al. M2 macrophage-derived exosomal miR-26b-5p regulates macrophage polarization and chondrocyte hypertrophy by targeting TLR3 and COL10A1 to alleviate osteoarthritis. J Nanobiotechnology. 2024; 22(1): 72.

[173] Gundra UM, Mishra BB, Wong K, Teale JM. Increased disease severity of parasite-infected TLR2-/-mice is correlated with decreased central nervous system inflammation and reduced numbers of cells with alternatively activated macrophage phenotypes in a murine model of neurocysticercosis. Infect Immun. 2011; 79(7): 2586-2596.

[174] Li W, Wang K, Liu Y, et al. A novel drug combination of mangiferin and cinnamic acid alleviates rheumatoid arthritis by inhibiting TLR4/NFκB/NLRP3 activation-induced pyroptosis. Front Immunol. 2022; 13: 912933.

[175] Li L, Pan Z, Ning D, Fu Y. Rosmanol and carnosol synergistically alleviate rheumatoid arthritis through inhibiting TLR4/NF-κB/MAPK pathway. Molecules. 2021; 27(1): 78.

[176] Dai W, Long L, Wang X, Li S, Xu H. Phytochemicals targeting Toll-like receptors 4 (TLR4) in inflammatory bowel disease. Chin Med. 2022; 17(1): 53.

[177] Liu B, Wang X, Chen TZ, et al. Polarization of M1 tumor associated macrophage promoted by the activation of TLR3 signal pathway. Asian Pac J Trop Med. 2016; 9(5): 484-488.

[178] Thomas G, Micci L, Yang W, et al. Intra-tumoral activation of endosomal TLR pathways reveals a distinct role for TLR3 agonist dependent type-1 interferons in shaping the tumor immune microenvironment. Front Oncol. 2021; 11: 711673.

[179] Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signal. 2014; 26(2): 192-197.

[180] Li L, Wei C, Cai S, Fang L. TRPM7 modulates macrophage polarization by STAT1/STAT6 pathways in RAW264.7 cells. Biochem Biophys Res Commun. 2020; 533(4): 692-697.

[181] Liu Y, Liu Z, Tang H, et al. The N(6)-methyladenosine (m(6)A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA. Am J Physiol Cell Physiol. 2019; 317(4): C762-C775.

[182] Jerke U, Tkachuk S, Kiyan J, et al. Stat1 nuclear translocation by nucleolin upon monocyte differentiation. PLoS One. 2009; 4(12): e8302.

[183] Chattopadhyay D, Das S, Guria S, Basu S, Mukherjee S. Fetuin-A regulates adipose tissue macrophage content and activation in insulin resistant mice through MCP-1 and iNOS: involvement of IFNγ-JAK2-STAT1 pathway. Biochem J. 2021; 478(22): 4027-4043.

[184] Yang T, Wang R, Liu H, et al. Berberine regulates macrophage polarization through IL-4-STAT6 signaling pathway in Helicobacter pylori-induced chronic atrophic gastritis. Life Sci. 2021; 266: 118903.

[185] Shi JH, Liu LN, Song DD, et al. TRAF3/STAT6 axis regulates macrophage polarization and tumor progression. Cell Death Differ. 2023; 30(8): 2005-2016.

[186] Huang C, Wang J, Liu H, et al. Ketone body β-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway. BMC Med. 2022; 20(1): 148.

[187] Rahal OM, Wolfe AR, Mandal PK, et al. Blocking interleukin (IL)4-and IL13-mediated phosphorylation of STAT6 (Tyr641) decreases M2 polarization of macrophages and protects against macrophage-mediated radioresistance of inflammatory breast cancer. Int J Radiat Oncol Biol Phys. 2018; 100(4): 1034-1043.

[188] Xiang X, Feng D, Hwang S, et al. Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming impaired regeneration pathways in mice. J Hepatol. 2020; 72(4): 736-745.

[189] Sun W, Wang Q, Zhang R, Zhang N. Ketogenic diet attenuates neuroinflammation and induces conversion of M1 microglia to M2 in an EAE model of multiple sclerosis by regulating the NF-κB/NLRP3 pathway and inhibiting HDAC3 and P2×7R activation. Food Funct. 2023; 14(15): 7247-7269.

[190] Covarrubias AJ, Aksoylar HI, Horng T. Control of macrophage metabolism and activation by mTOR and Akt signaling. Semin Immunol. 2015; 27(4): 286-296.

[191] Donninelli G, Saraf-Sinik I, Mazziotti V, et al. Interleukin-9 regulates macrophage activation in the progressive multiple sclerosis brain. J Neuroinflammation. 2020; 17(1): 149.

[192] Geng T, Yan Y, Xu L, et al. CD137 signaling induces macrophage M2 polarization in atherosclerosis through STAT6/PPARδ pathway. Cell Signal. 2020; 72: 109628.

[193] Gong M, Zhuo X, Ma A. STAT6 upregulation promotes M2 macrophage polarization to suppress atherosclerosis. Med Sci Monit Basic Res. 2017; 23: 240-249.

[194] Czimmerer Z, Nagy L. Epigenomic regulation of macrophage polarization: Where do the nuclear receptors belong? Immunol Rev. 2023; 317(1): 152-165.

[195] Tu Y, Liu J, Kong D, et al. Irisin drives macrophage anti-inflammatory differentiation via JAK2-STAT6-dependent activation of PPARγ and Nrf2 signaling. Free Radic Biol Med. 2023; 201: 98-110.

[196] Sharma S, Shen T, Chitranshi N, et al. Retinoid X receptor: cellular and biochemical roles of nuclear receptor with a focus on neuropathological involvement. Mol Neurobiol. 2022; 59(4): 2027-2050.

[197] He L, Jhong JH, Chen Q, et al. Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors. Cell Rep. 2021; 37(5): 109955.

[198] Yu T, Gao M, Yang P, et al. Insulin promotes macrophage phenotype transition through PI3K/Akt and PPAR-γ signaling during diabetic wound healing. J Cell Physiol. 2019; 234(4): 4217-4231.

[199] Xu M, Wang X, Li Y, et al. Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARγ dependent manner. Front Immunol. 2021; 12: 618501.

[200] Ding H, Dong J, Wang Y, et al. Ginsenoside Rb1 interfered with macrophage activation by activating PPARγ to inhibit insulin resistance in obesity. Molecules. 2023; 28(7): 3083.

[201] de la Aleja AG, Herrero C, Torres-Torresano M, et al. Inhibition of LXR controls the polarization of human inflammatory macrophages through upregulation of MAFB. Cell Mol Life Sci. 2023; 80(4): 96.

[202] Dong XC. Sirtuin 6—a key regulator of hepatic lipid metabolism and liver health. Cells. 2023; 12(4): 663.

[203] Zhang X, McDonald JG, Aryal B, et al. Desmosterol suppresses macrophage inflammasome activation and protects against vascular inflammation and atherosclerosis. Proc Natl Acad Sci USA. 2021; 118(47): e2107682118.

[204] Li X, Huang X, Feng Y, et al. Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway. Eur J Pharmacol. 2023; 950: 175771.

[205] Oishi Y, Spann NJ, Link VM, et al. SREBP1 contributes to resolution of pro-inflammatory TLR4 signaling by reprogramming fatty acid metabolism. Cell Metab. 2017; 25(2): 412-427.

[206] Chuang ST, Stein JB, Nevins S, et al. Enhancing CAR macrophage efferocytosis via surface engineered lipid nanoparticles targeting LXR signaling. Adv Mater. 2024; 36(19): e2308377.

[207] Babuta M, Szabo G. Extracellular vesicles in inflammation: focus on the microRNA cargo of EVs in modulation of liver diseases. J Leukoc Biol. 2022; 111(1): 75-92.

[208] Nandan D, Rath CT, Reiner NE. Leishmania regulates host macrophage miRNAs expression by engaging transcription factor c-Myc. J Leukoc Biol. 2021; 109(5): 999-1007.

[209] Yang B, Lin Y, Huang Y, Zhu N, Shen Y-Q. Extracellular vesicles modulate key signalling pathways in refractory wound healing. Burns Trauma. 2023; 11: tkad039.

[210] Ye J, Kang Y, Sun X, Ni P, Wu M, Lu S. MicroRNA-155 inhibition promoted wound healing in diabetic rats. Int J Low Extrem Wounds. 2017; 16(2): 74-84.

[211] Chachques JC, Gardin C, Lila N, et al. Elastomeric cardiowrap scaffolds functionalized with mesenchymal stem cells-derived exosomes induce a positive modulation in the inflammatory and wound healing response of mesenchymal stem cell and macrophage. Biomedicines. 2021; 9(7): 824.

[212] Zheng L, Su J, Zhang Z, et al. Salidroside regulates inflammatory pathway of alveolar macrophages by influencing the secretion of miRNA-146a exosomes by lung epithelial cells. Sci Rep. 2020; 10(1): 20750.

[213] Bala S, Csak T, Saha B, et al. The pro-inflammatory effects of miR-155 promote liver fibrosis and alcohol-induced steatohepatitis. J Hepatol. 2016; 64(6): 1378-1387.

[214] Gao Y, Han T, Han C, et al. Propofol regulates the TLR4/NF-κB pathway through miRNA-155 to protect colorectal cancer intestinal barrier. Inflammation. 2021; 44(5): 2078-2090.

[215] Chaudhuri AA, So AY, Sinha N, et al. MicroRNA-125b potentiates macrophage activation. J Immunol. 2011; 187(10): 5062-5068.

[216] Peng X, He F, Mao Y, et al. miR-146a promotes M2 macrophage polarization and accelerates diabetic wound healing by inhibiting the TLR4/NF-κB axis. J Mol Endocrinol. 2022; 69(2): 315-327.

[217] Li R, Zhao K, Ruan Q, Meng C, Yin F. Bone marrow mesenchymal stem cell-derived exosomal microRNA-124-3p attenuates neurological damage in spinal cord ischemia-reperfusion injury by downregulating Ern1 and promoting M2 macrophage polarization. Arthritis Res Ther. 2020; 22(1): 75.

[218] Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway. Nat Med. 2011; 17(1): 64-70.

[219] Ding N, Luo G, Li H, et al. A cyclodextrin-based ph-responsive microRNA delivery platform targeting polarization of M1 to M2 macrophages for sepsis therapy. Adv Healthc Mater. 2023; 12(27): e2301243.

[220] Ying W, Tseng A, Chang RC, et al. MicroRNA-223 is a crucial mediator of PPARγ-regulated alternative macrophage activation. J Clin Invest. 2015; 125(11): 4149-4159.

[221] Amoruso A, Blonda M, Gironi M, et al. Immune and central nervous system-related miRNAs expression profiling in monocytes of multiple sclerosis patients. Sci Rep. 2020; 10(1): 6125.

[222] Paoletti A, Ly B, Cailleau C, et al. Liposomal AntagomiR-155-5p restores anti-inflammatory macrophages and improves arthritis in preclinical models of rheumatoid arthritis. Arthritis Rheumatol. 2024; 76(1): 18-31.

[223] Li ZL, Yang BC, Gao M, Xiao XF, Zhao SP, Liu ZL. Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis. Mol Ther Nucleic Acids. 2021; 25: 502-514.

[224] Jing C, Castro-Dopico T, Richoz N, et al. Macrophage metabolic reprogramming presents a therapeutic target in lupus nephritis. Proc Natl Acad Sci USA. 2020; 117(26): 15160-15171.

[225] Wang Z, Zhao F, Xu C, et al. Metabolic reprogramming in skin wound healing. Burns Trauma. 2024; 12: tkad047.

[226] Mouton AJ, Li X, Hall ME, Hall JE. Obesity, hypertension, and cardiac dysfunction: novel roles of immunometabolism in macrophage activation and inflammation. Circ Res. 2020; 126(6): 789-806.

[227] Wang F, Zhang S, Vuckovic I, et al. Glycolytic stimulation is not a requirement for M2 macrophage differentiation. Cell Metab. 2018; 28(3): 463-475. e4.

[228] Liu T, Wen Z, Shao L, et al. ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1α ubiquitination in sepsis. Clin Immunol. 2023; 254: 109698.

[229] Zhong WJ, Liu T, Yang HH, et al. TREM-1 governs NLRP3 inflammasome activation of macrophages by firing up glycolysis in acute lung injury. Int J Biol Sci. 2023; 19(1): 242-257.

[230] Tian S, Tan S, Fan M, et al. Hypoxic environment of wounds and photosynthesis-based oxygen therapy. Burns Trauma. 2024; 12: tkae012.

[231] Jin L, Zhou S, Zhao S, et al. Early short-term hypoxia promotes epidermal cell migration by activating the CCL2-ERK1/2 pathway and epithelial–mesenchymal transition during wound healing. Burns Trauma. 2024; 12: tkae017.

[232] Nascimento Júnior JXD, Sola-Penna M, Zancan P. Clotrimazole reverses macrophage M2 polarization by disrupting the PI3K/AKT/mTOR pathway. Biochem Biophys Res Commun. 2024; 696: 149455.

[233] Cui Y, Chen J, Zhang Z, Shi H, Sun W, Yi Q. The role of AMPK in macrophage metabolism, function and polarisation. J Transl Med. 2023; 21(1): 892.

[234] Cheng JW, Yu Y, Zong SY, et al. Berberine ameliorates collagen-induced arthritis in mice by restoring macrophage polarization via AMPK/mTORC1 pathway switching glycolytic reprogramming. Int Immunopharmacol. 2023; 124(Pt B):111024.

[235] Yang Y, Wang J, Guo S, et al. Non-lethal sonodynamic therapy facilitates the M1-to-M2 transition in advanced atherosclerotic plaques via activating the ROS-AMPK-mTORC1-autophagy pathway. Redox Biol. 2020; 32: 101501.

[236] Feng X, Chen W, Ni X, et al. Metformin, macrophage dysfunction and atherosclerosis. Front Immunol. 2021; 12: 682853.

[237] Kim YS, Park BS, Baek HS, Kang HM, Oh JM, Kim IR. Metformin activates AMPK and mTOR to Inhibit RANKL-stimulated osteoclast formation. Eur Rev Med Pharmacol Sci. 2023; 27(18): 8795-8811.

[238] Liu S, Zhang H, Li Y, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation. J Immunother Cancer. 2021; 9(6): e002548.

[239] Xiao S, Qi M, Zhou Q, et al. Macrophage fatty acid oxidation in atherosclerosis. Biomed Pharmacother. 2024; 170: 116092.

[240] Chang L, Gao J, Yu Y, et al. MMP10 alleviates non-alcoholic steatohepatitis by regulating macrophage M2 polarization. Int Immunopharmacol. 2023; 124(Pt B):111045.

[241] Chen X, He Y, Fu W, et al. Histone deacetylases (HDACs) and atherosclerosis: a mechanistic and pharmacological review. Front Cell Dev Biol. 2020; 8: 581015.

[242] Das Gupta K, Shakespear MR, Iyer A, Fairlie DP, Sweet MJ. Histone deacetylases in monocyte/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases. Clin Transl Immunol. 2016; 5(1): e62.

[243] Karnam K, Sedmaki K, Sharma P, Mahale A, Ghosh B, Kulkarni OP. Pharmacological blockade of HDAC3 accelerates diabetic wound healing by regulating macrophage activation. Life Sci. 2023; 321: 121574.

[244] Ghiboub M, Zhao J, Li Yim AYF, et al. HDAC3 mediates the inflammatory response and LPS tolerance in human monocytes and macrophages. Front Immunol. 2020; 11: 550769.

[245] Xu L, An T, Jia B, et al. Histone deacetylase 3-specific inhibitor RGFP966 attenuates oxidative stress and inflammation after traumatic brain injury by activating the Nrf2 pathway. Burns Trauma. 2024; 12: tkad062.

[246] Kang H, Kim S, Lee JY, Kim B. Inhibitory effects of ginsenoside compound K on lipopolysaccharide-stimulated inflammatory responses in macrophages by regulating sirtuin 1 and histone deacetylase 4. Nutrients. 2023; 15(7): 1626.

[247] Kang H, Park YK, Lee JY. Inhibition of alcohol-induced inflammation and oxidative stress by astaxanthin is mediated by its opposite actions in the regulation of sirtuin 1 and histone deacetylase 4 in macrophages. Biochim Biophys Acta Mol Cell Biol Lipids. 2021; 1866(1): 158838.

[248] Zhao Y, Ma G, Yang X. HDAC5 promotes Mycoplasma pneumoniae-induced inflammation in macrophages through NF-κB activation. Life Sci. 2019; 221: 13-19.

[249] Poralla L, Stroh T, Erben U, et al. Histone deacetylase 5 regulates the inflammatory response of macrophages. J Cell Mol Med. 2015; 19(9): 2162-2171.

[250] Yang X, Wang X, Liu D, Yu L, Xue B, Shi H. Epigenetic regulation of macrophage polarization by DNA methyltransferase 3b. Mol Endocrinol. 2014; 28(4): 565-574.

[251] Li HD, Chen X, Xu JJ, et al. DNMT3b-mediated methylation of ZSWIM3 enhances inflammation in alcohol-induced liver injury via regulating TRAF2-mediated NF-κB pathway. Clin Sci (Lond). 2020; 134(14): 1935-1956.

[252] Li B, Huo Y, Lin Z, Wang T. [DNA hydroxymethylase 10–11 translocation 2 (TET2) inhibits mouse macrophage activation and polarization]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017; 33(9): 1165-1170.

[253] Li C, Xu MM, Wang K, Adler AJ, Vella AT, Zhou B. Macrophage polarization and meta-inflammation. Transl Res. 2018; 191: 29-44.

[254] Yu H, Pan J, Zheng S, et al. Hepatocellular carcinoma cell-derived exosomal miR-21-5p induces macrophage M2 polarization by targeting RhoB. Int J Mol Sci. 2023; 24(5): 4593.

[255] Wang Q, Xie Y, He Q, Geng Y, Xu J. LncRNA-Cox2 regulates macrophage polarization and inflammatory response through the CREB-C/EBPβ signaling pathway in septic mice. Int Immunopharmacol. 2021; 101(Pt B):108347.

[256] Du M, Yuan L, Tan X, et al. The LPS-inducible lncRNA Mirt2 is a negative regulator of inflammation. Nat Commun. 2017; 8(1): 2049.

[257] Chistiakov DA, Myasoedova VA, Revin VV, Orekhov AN, Bobryshev YV. The impact of interferon-regulatory factors to macrophage differentiation and polarization into M1 and M2. Immunobiology. 2018; 223(1): 101-111.

[258] Zhu X, Guo Q, Zou J, et al. MiR-19a-3p suppresses M1 macrophage polarization by inhibiting STAT1/IRF1 pathway. Front Pharmacol. 2021; 12: 614044.

[259] Bian J, Zhu Y, Tian P, Yang Q, Li Z. Adaptor protein HIP-55 promotes macrophage M1 polarization through promoting AP-1 complex activation. Cell Signal. 2024; 117: 111124.

[260] Tan S, Wang Z, Li N, et al. Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response. Cell Death Differ. 2023; 30(9): 2104-2119.

[261] Kroner A, Greenhalgh AD, Zarruk JG, Passos Dos Santos R, Gaestel M, David S. TNF and increased intracellular iron alter macrophage polarization to a detrimental M1 phenotype in the injured spinal cord. Neuron. 2014; 83(5): 1098-1116.

[262] Wang X, Cao Q, Yu L, Shi H, Xue B, Shi H. Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity. JCI Insight. 2016; 1(19): e87748.

[263] Tang RZ, Zhu JJ, Yang FF, et al. DNA methyltransferase 1 and Krüppel-like factor 4 axis regulates macrophage inflammation and atherosclerosis. J Mol Cell Cardiol. 2019; 128: 11-24.

[264] Li J, Ye F, Xu X, et al. Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade. J Nanobiotechnology. 2023; 21(1): 280.

[265] Mullican SE, Gaddis CA, Alenghat T, et al. Histone deacetylase 3 is an epigenomic brake in macrophage alternative activation. Genes Dev. 2011; 25(23): 2480-2488.

[266] Zhou X, Chen H, Shi Y, et al. Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization. Front Immunol. 2023; 14: 1137332.

[267] Das Gupta K, Ramnath D, von Pein JB, et al. HDAC7 is an immunometabolic switch triaging danger signals for engagement of antimicrobial versus inflammatory responses in macrophages. Proc Natl Acad Sci USA. 2023; 120(4): e2212813120.

[268] Schiano C, Benincasa G, Franzese M, et al. Epigenetic-sensitive pathways in personalized therapy of major cardiovascular diseases. Pharmacol Ther. 2020; 210: 107514.

[269] Zhong C, Tao B, Yang F, et al. Histone demethylase JMJD1C promotes the polarization of M1 macrophages to prevent glioma by upregulating miR-302a. Clin Transl Med. 2021; 11(9): e424.

[270] Li H, Hu W, Lin Y, Xu T, Zhang X, Wang C. MicroRNA-9-5p is involved in lipopolysaccharide-induced acute lung injury via the regulation of macrophage polarization. Int J Toxicol. 2023; 42(2): 156-164.

[271] Liu X, Mao Y, Kang Y, et al. MicroRNA-127 promotes anti-microbial host defense through restricting A20-mediated de-ubiquitination of STAT3. iScience. 2020; 23(1): 100763.

[272] Zhang P, Wang H, Luo X, et al. MicroRNA-155 inhibits polarization of macrophages to M2-type and suppresses choroidal neovascularization. Inflammation. 2018; 41(1): 143-153.

[273] Yu T, Gan S, Zhu Q, et al. Modulation of M2 macrophage polarization by the crosstalk between Stat6 and Trim24. Nat Commun. 2019; 10(1): 4353.

[274] Zhao C, Zeng N, Zhou X, et al. CAA-derived IL-6 induced M2 macrophage polarization by activating STAT3. BMC Cancer. 2023; 23(1): 392.

[275] Liu M, Tong Z, Ding C, et al. Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer. J Clin Invest. 2020; 130(4): 2081-2096.

[276] Li W, Wang Y, Zhu L, et al. The P300/XBP1s/Herpud1 axis promotes macrophage M2 polarization and the development of choroidal neovascularization. J Cell Mol Med. 2021; 25(14): 6709-6720.

[277] denDekker AD, Davis FM, Joshi AD, et al. TNF-α regulates diabetic macrophage function through the histone acetyltransferase MOF. JCI Insight. 2020; 5(5): e132306.

[278] Zhang M, Hei R, Zhou Z, Xiao W, Liu X, Chen Y. Macrophage polarization involved the inflammation of chronic obstructive pulmonary disease by S1P/HDAC1 signaling. Am J Cancer Res. 2023; 13(9): 4478-4489.

[279] Zheng X, Sarode P, Weigert A, et al. The HDAC2-SP1 axis orchestrates protumor macrophage polarization. Cancer Res. 2023; 83(14): 2345-2357.

[280] Xu G, Niu L, Wang Y, et al. HDAC6-dependent deacetylation of TAK1 enhances sIL-6R release to promote macrophage M2 polarization in colon cancer. Cell Death Dis. 2022; 13(10): 888.

[281] Zhong Y, Huang T, Huang J, et al. The HDAC10 instructs macrophage M2 program via deacetylation of STAT3 and promotes allergic airway inflammation. Theranostics. 2023; 13(11): 3568-3581.

[282] Luan B, Goodarzi MO, Phillips NG, et al. Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4. Cell Metab. 2014; 19(6): 1058-1065.

[283] Peng W, Xie Y, Luo Z, et al. UTX deletion promotes M2 macrophage polarization by epigenetically regulating endothelial cell-macrophage crosstalk after spinal cord injury. J Nanobiotechnology. 2023; 21(1): 225.

[284] Lee JY, Mehrazarin S, Alshaikh A, et al. Histone Lys demethylase KDM3C demonstrates anti-inflammatory effects by suppressing NF-κB signaling and osteoclastogenesis. Faseb J. 2019; 33(9): 10515-10527.

[285] Liu T, Zhang Z, Shen W, Wu Y, Bian T. MicroRNA Let-7 induces M2 macrophage polarization in COPD emphysema through the IL-6/STAT3 pathway. Int J Chron Obstruct Pulmon Dis. 2023; 18: 575-591.

[286] Li Y, Chen X, Jin R, et al. Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs. Sci Adv. 2021; 7(9): eabd6740.

[287] Zhao G, Yu H, Ding L, et al. microRNA-27a-3p delivered by extracellular vesicles from glioblastoma cells induces M2 macrophage polarization via the EZH1/KDM3A/CTGF axis. Cell Death Discov. 2022; 8(1): 260.

[288] Ghorbani S, Talebi F, Chan WF, et al. MicroRNA-181 variants regulate T cell phenotype in the context of autoimmune neuroinflammation. Front Immunol. 2017; 8: 758.

[289] Spinosa M, Lu G, Su G, et al. Human mesenchymal stromal cell-derived extracellular vesicles attenuate aortic aneurysm formation and macrophage activation via microRNA-147. Faseb J. 2018; 32(11):fj201701138RR.

[290] Wang Y, Han B, Wang Y, et al. Mesenchymal stem cell-secreted extracellular vesicles carrying TGF-β1 up-regulate miR-132 and promote mouse M2 macrophage polarization. J Cell Mol Med. 2020; 24(21): 12750-12764.

[291] Freemerman AJ, Johnson AR, Sacks GN, et al. Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype. J Biol Chem. 2014; 289(11): 7884-7896.

[292] Hou Y, Wei D, Zhang Z, et al. FABP5 controls macrophage alternative activation and allergic asthma by selectively programming long-chain unsaturated fatty acid metabolism. Cell Rep. 2022; 41(7): 111668.

[293] Kieler M, Hofmann M, Schabbauer G. More than just protein building blocks: how amino acids and related metabolic pathways fuel macrophage polarization. Febs j. 2021; 288(12): 3694-3714.

[294] Pereira M, Chen TD, Buang N, et al. Acute iron deprivation reprograms human macrophage metabolism and reduces inflammation in vivo. Cell Rep. 2019; 28(2): 498-511. e5.

[295] Tardito S, Martinelli G, Soldano S, et al. Macrophage M1/M2 polarization and rheumatoid arthritis: a systematic review. Autoimmun Rev. 2019; 18(11): 102397.

[296] Peng Y, Zhou M, Yang H, et al. Regulatory mechanism of M1/M2 macrophage polarization in the development of autoimmune diseases. Mediators Inflamm. 2023; 2023: 8821610.

[297] Zhang K, Guo J, Yan W, Xu L. Macrophage polarization in inflammatory bowel disease. Cell Commun Signal. 2023; 21(1): 367.

[298] Du Y, Rong L, Cong Y, Shen L, Zhang N, Wang B. Macrophage polarization: an effective approach to targeted therapy of inflammatory bowel disease. Expert Opin Ther Targets. 2021; 25(3): 191-209.

[299] Gao J, Liang Y, Wang L. Shaping polarization of tumor-associated macrophages in cancer immunotherapy. Front Immunol. 2022; 13: 888713.

[300] Akkari L, Bowman RL, Tessier J, et al. Dynamic changes in glioma macrophage populations after radiotherapy reveal CSF-1R inhibition as a strategy to overcome resistance. Sci Transl Med. 2020; 12(552): eaaw7843.

[301] Hu Q, Wu G, Wang R, Ma H, Zhang Z, Xue Q. Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer. Front Immunol. 2022; 13: 1007812.

[302] Liu X, Hogg GD, Zuo C, et al. Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity. Cancer Cell. 2023; 41(6): 1073-1090. e12.

[303] Li LG, Yang XX, Xu HZ, et al. A dihydroartemisinin-loaded nanoreactor motivates anti-cancer immunotherapy by synergy-induced ferroptosis to activate Cgas/STING for reprogramming of macrophage. Adv Healthc Mater. 2023; 12(28): e2301561.

[304] Yu DM, Zhao J, Lee EE, et al. GLUT3 promotes macrophage signaling and function via RAS-mediated endocytosis in atopic dermatitis and wound healing. J Clin Invest. 2023; 133(21): e170706.

[305] Shirakawa K, Endo J, Kataoka M, et al. IL (interleukin)-10-STAT3-galectin-3 axis is essential for osteopontin-producing reparative macrophage polarization after myocardial infarction. Circulation. 2018; 138(18): 2021-2035.

[306] Zhang SM, Wei CY, Wang Q, Wang L, Lu L, Qi FZ. M2-polarized macrophages mediate wound healing by regulating connective tissue growth factor via AKT, ERK1/2, and STAT3 signaling pathways. Mol Biol Rep. 2021; 48(9): 6443-6456.

[307] Gong T, Liu L, Jiang W, Zhou R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Nat Rev Immunol. 2020; 20(2): 95-112.

[308] Zindel J, Kubes P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu Rev Pathol. 2020; 15: 493-518.

[309] Geng J, Shi Y, Zhang J, et al. TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection. Nat Commun. 2021; 12(1): 3519.

[310] Li D, Wu M. Pattern recognition receptors in health and diseases. Signal Transduct Target Ther. 2021; 6(1): 291.

[311] Zumerle S, Calì B, Munari F, et al. Intercellular calcium signaling induced by ATP potentiates macrophage phagocytosis. Cell Rep. 2019; 27(1): 1-10. e4.

[312] Tan F, Cao Y, Zheng L, et al. Diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization via miR-3061/Snail1 signaling. Front Immunol. 2022; 13: 922614.

[313] Wang E-J, Wu M-Y, Ren Z-Y, et al. Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease. Burns Trauma. 2023; 11: tkad004.

[314] Boada-Romero E, Martinez J, Heckmann BL, Green DR. The clearance of dead cells by efferocytosis. Nat Rev Mol Cell Biol. 2020; 21(7): 398-414.

[315] Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol. 2020; 877: 173090.

[316] Aderem A, Underhill DM. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999; 17: 593-623.

[317] Pidwill GR, Gibson JF, Cole J, Renshaw SA, Foster SJ. The role of macrophages in Staphylococcus aureus infection. Front Immunol. 2020; 11: 620339.

[318] Small AG, Harvey S, Kaur J, et al. Vitamin D upregulates the macrophage complement receptor immunoglobulin in innate immunity to microbial pathogens. Commun Biol. 2021; 4(1): 401.

[319] Minhas R, Bansal Y, Bansal G. Inducible nitric oxide synthase inhibitors: a comprehensive update. Med Res Rev. 2020; 40(3): 823-855.

[320] Tsai CF, Chen GW, Chen YC, et al. Regulatory effects of quercetin on M1/M2 macrophage polarization and oxidative/antioxidative balance. Nutrients. 2021; 14(1): 67.

[321] Sivaraman K, Wrenger S, Liu B, et al. Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin. J Leukoc Biol. 2023; 113(1): 58-70.

[322] Monteith AJ, Miller JM, Maxwell CN, Chazin WJ, Skaar EP. Neutrophil extracellular traps enhance macrophage killing of bacterial pathogens. Sci Adv. 2021; 7(37): eabj2101.

[323] Nagaoka I, Tamura H, Reich J. Therapeutic potential of cathelicidin peptide LL-37, an antimicrobial agent, in a murine sepsis model. Int J Mol Sci. 2020; 21(17): 5973.

[324] Szulc-Dąbrowska L, Bossowska-Nowicka M, Struzik J, Toka FN. Cathepsins in bacteria-macrophage interaction: defenders or victims of circumstance? Front Cell Infect Microbiol. 2020; 10: 601072.

[325] Weiss G, Schaible UE. Macrophage defense mechanisms against intracellular bacteria. Immunol Rev. 2015; 264(1): 182-203.

[326] Rai R, Singh V, Mathew BJ, Singh AK, Chaurasiya SK. Mycobacterial response to an acidic environment: protective mechanisms. Pathog Dis. 2022; 80(1): ftac032.

[327] Demkow U. Molecular mechanisms of neutrophil extracellular trap (NETs) degradation. Int J Mol Sci. 2023; 24(5): 4896.

[328] Korobova ZR, Arsentieva NA, Totolian AA. Macrophage-derived chemokine MDC/CCL22: an ambiguous finding in COVID-19. Int J Mol Sci. 2023; 24(17): 13083.

[329] Hurme P, Komulainen M, Tulkki M, et al. Cytokine expression in rhinovirus-vs. respiratory syncytial virus-induced first wheezing episode and its relation to clinical course. Front Immunol. 2022; 13: 1044621.

[330] Jin H, Wen X, Sun R, et al. Engineered nanovesicles from activated neutrophils with enriched bactericidal proteins have molecular debridement ability and promote infectious wound healing. Burns Trauma. 2024; 12: tkae018.

[331] Mass E, Nimmerjahn F, Kierdorf K, Schlitzer A. Tissue-specific macrophages: how they develop and choreograph tissue biology. Nat Rev Immunol. 2023; 23(9): 563-579.

[332] McCubbrey AL, McManus SA, McClendon JD, et al. Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells. Cell Rep. 2022; 38(2): 110222.

[333] Chang M, Nguyen TT. Strategy for treatment of infected diabetic foot ulcers. Acc Chem Res. 2021; 54(5): 1080-1093.

[334] Moretti L, Stalfort J, Barker TH, Abebayehu D. The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation. J Biol Chem. 2022; 298(2): 101530.

[335] Maassen S, Coenen B, Ioannidis M, et al. Itaconate promotes a wound resolving phenotype in pro-inflammatory macrophages. Redox Biol. 2023; 59: 102591.

[336] Zeng L, Zhou S, Chen C, et al. Experimental study of fat derived pellets promoting wound healing in rats. Bioengineered. 2021; 12(2): 12323-12331.

[337] Vannella KM, Wynn TA. Mechanisms of organ injury and repair by macrophages. Annu Rev Physiol. 2017; 79: 593-617.

[338] Jung M, Ma Y, Iyer RP, et al. IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. Basic Res Cardiol. 2017; 112(3): 33.

[339] Steen EH, Wang X, Balaji S, Butte MJ, Bollyky PL, Keswani SG. The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis. Adv Wound Care (New Rochelle). 2020; 9(4): 184-198.

[340] Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med. 2020; 217(1): e20190418.

[341] Minton K. Immune regulation: IL-10 targets macrophage metabolism. Nat Rev Immunol. 2017; 17(6): 345.

[342] Wang J, Chen G, Li L, et al. Sustained induction of IP-10 by MRP8/14 via the IFNβ–IRF7 axis in macrophages exaggerates lung injury in endotoxemic mice. Burns Trauma. 2023; 11: tkad006.

[343] Liu J, Wang H, Zhang L, et al. Periodontal ligament stem cells promote polarization of M2 macrophages. J Leukoc Biol. 2022; 111(6): 1185-1197.

[344] Wang J, Zhao X, Wan YY. Intricacies of TGF-β signaling in Treg and Th17 cell biology. Cell Mol Immunol. 2023; 20(9): 1002-1022.

[345] De Nardo D, Labzin LI, Kono H, et al. High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol. 2014; 15(2): 152-160.

[346] Petta I, Thorp M, Ciers M, et al. Myeloid A20 is critical for alternative macrophage polarization and type-2 immune-mediated helminth resistance. Front Immunol. 2024; 15: 1373745.

[347] Zheng Y, Wang S, Zhong Y, Huang C, Wu X. A20 affects macrophage polarization through the NLRP3 inflammasome signaling pathway and promotes breast cancer progression. Exp Ther Med. 2023; 25(4): 147.

[348] Panigrahy D, Gilligan MM, Serhan CN, Kashfi K. Resolution of inflammation: an organizing principle in biology and medicine. Pharmacol Ther. 2021; 227: 107879.

[349] Martin P, Gurevich DB. Macrophage regulation of angiogenesis in health and disease. Semin Cell Dev Biol. 2021; 119: 101-110.

[350] Hadrian K, Willenborg S, Bock F, Cursiefen C, Eming SA, Hos D. Macrophage-mediated tissue vascularization: similarities and differences between cornea and skin. Front Immunol. 2021; 12: 667830.

[351] Huang X, Zheng L, Zhou Y, et al. Controllable adaptive molybdate-oligosaccharide nanoparticles regulate M2 macrophage mitochondrial function and promote angiogenesis via PI3K/HIF-1α/VEGF pathway to accelerate diabetic wound healing. Adv Healthc Mater. 2024; 13(3): e2302256.

[352] Du H, Li S, Lu J, et al. Single-cell RNA-seq and bulk-seq identify RAB17 as a potential regulator of angiogenesis by human dermal microvascular endothelial cells in diabetic foot ulcers. Burns Trauma. 2023; 11: tkad020.

[353] Song X, Chen Y, Chen X, et al. Exosomes from tannic acid-stimulated macrophages accelerate wound healing through miR-221-3p mediated fibroblasts migration by targeting CDKN1b. Int J Biol Macromol. 2023; 244: 125088.

[354] Laplante P, Brillant-Marquis F, Brissette MJ, et al. MFG-E8 reprogramming of macrophages promotes wound healing by increased bFGF production and fibroblast functions. J Invest Dermatol. 2017; 137(9): 2005-2013.

[355] Zhu L, Qian J, Jiang Y, Yang T, Duan Q, Xiao X. PlGF reduction compromises angiogenesis in diabetic foot disease through macrophages. Front Immunol. 2021; 12: 736153.

[356] White MJV, Briquez PS, White DAV, Hubbell JA. VEGF-A, PDGF-BB and HB-EGF engineered for promiscuous super affinity to the extracellular matrix improve wound healing in a model of type 1 diabetes. NPJ Regen Med. 2021; 6(1): 76.

[357] Song Y, Yang J, Li T, et al. CD34(+) cell-derived fibroblast-macrophage cross-talk drives limb ischemia recovery through the OSM-ANGPTL signaling axis. Sci Adv. 2023; 9(15): eadd2632.

[358] Lapkina EZ, Esimbekova AR, Ruksha TG. [Vasculogenic mimicry]. Arkh Patol. 2023; 85(6): 62-69.

[359] Senk A, Fazzari J, Djonov V. Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels. Angiogenesis. 2024.

[360] Yan D, He Y, Dai J, Yang L, Wang X, Ruan Q. Vascular endothelial growth factor modified macrophages transdifferentiate into endothelial-like cells and decrease foam cell formation. Biosci Rep. 2017; 37(3): BSR20170002.

[361] Bai H, Xie B, Li M, et al. Biodegraded PCl and gelatin fabricated vascular patch in rat aortic and inferior vena cava angioplasty. Microvasc Res. 2022; 141: 104314.

[362] Forrest OA, Dobosh B, Ingersoll SA, et al. Neutrophil-derived extracellular vesicles promote feed-forward inflammasome signaling in cystic fibrosis airways. J Leukoc Biol. 2022; 112(4): 707-716.

[363] Talbott HE, Mascharak S, Griffin M, Wan DC, Longaker MT. Wound healing, fibroblast heterogeneity, and fibrosis. Cell Stem Cell. 2022; 29(8): 1161-1180.

[364] El Ayadi A, Jay JW, Prasai A. Current approaches targeting the wound healing phases to attenuate fibrosis and scarring. Int J Mol Sci. 2020; 21(3): 1105.

[365] Shi T, Denney L, An H, Ho LP, Zheng Y. Alveolar and lung interstitial macrophages: definitions, functions, and roles in lung fibrosis. J Leukoc Biol. 2021; 110(1): 107-114.

[366] Wang J, Shang R, Yang J, et al. P311 promotes type II transforming growth factor-β receptor mediated fibroblast activation and granulation tissue formation in wound healing. Burns Trauma. 2022; 10: tkac027.

[367] Wang Y, Zhang L, Wu GR, et al. MBD2 serves as a viable target against pulmonary fibrosis by inhibiting macrophage M2 program. Sci Adv. 2021; 7(1): eabb6075.

[368] Huang C, Ogawa R. Role of inflammasomes in keloids and hypertrophic scars-lessons learned from chronic diabetic wounds and skin fibrosis. Int J Mol Sci. 2022; 23(12): 6820.

[369] Setten E, Castagna A, Nava-Sedeño JM, et al. Understanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context. Nat Commun. 2022; 13(1): 6499.

[370] Liu Q, Yang Q, Wu Z, et al. IL-1β-activated mTORC2 promotes accumulation of IFN-γ(+) γδ T cells by upregulating CXCR3 to restrict hepatic fibrosis. Cell Death Dis. 2022; 13(4): 289.

[371] Simões FC, Cahill TJ, Kenyon A, et al. Macrophages directly contribute collagen to scar formation during zebrafish heart regeneration and mouse heart repair. Nat Commun. 2020; 11(1): 600.

[372] Zhu H, Fu J, Chen S, et al. FC-99 reduces macrophage tenascin-C expression by upregulating miRNA-494 in arthritis. Int Immunopharmacol. 2020; 79: 106105.

[373] Okada T, Suzuki H. The role of tenascin-C in tissue injury and repair after stroke. Front Immunol. 2020; 11: 607587.

[374] Chen K, Rao Z, Dong S, et al. Roles of the fibroblast growth factor signal transduction system in tissue injury repair. Burns Trauma. 2022; 10: tkac005.

[375] Liu C, Pei M, Li Q, Zhang Y. Decellularized extracellular matrix mediates tissue construction and regeneration. Front Med. 2022; 16(1): 56-82.

[376] Huang J, Heng S, Zhang W, et al. Dermal extracellular matrix molecules in skin development, homeostasis, wound regeneration and diseases. Semin Cell Dev Biol. 2022; 128: 137-144.

[377] Dai S, Xu M, Pang Q, et al. Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids. Burns Trauma. 2024; 12: tkad036.

[378] Zhao X, Chen J, Sun H, Zhang Y, Zou D. New insights into fibrosis from the ECM degradation perspective: the macrophage-MMP-ECM interaction. Cell Biosci. 2022; 12(1): 117.

[379] He L, Kang Q, Chan KI, Zhang Y, Zhong Z, Tan W. The immunomodulatory role of matrix metalloproteinases in colitis-associated cancer. Front Immunol. 2022; 13: 1093990.

[380] Travnickova J, Nhim S, Abdellaoui N, et al. Macrophage morphological plasticity and migration is Rac signalling and MMP9 dependant. Sci Rep. 2021; 11(1): 10123.

[381] Wang X, Zhang D, Fucci QA, Dollery CM, Owen CA. Surface-bound matrix metalloproteinase-8 on macrophages: Contributions to macrophage pericellular proteolysis and migration through tissue barriers. Physiol Rep. 2021; 9(5): e14778.

[382] Qiu L, Wang Y, Wang Y, et al. Ursolic acid ameliorated neuronal damage by restoring microglia-activated MMP/TIMP imbalance in vitro. Drug Des Devel Ther. 2023; 17: 2481-2493.

[383] Ishida Y, Kuninaka Y, Nosaka M, et al. Immunohistochemical analysis on MMP-2 and MMP-9 for wound age determination. Int J Legal Med. 2015; 129(5): 1043-1048.

[384] Cecchi R, Tomoya I, Camatti J, Mizuho N, Yuko I, Toshikazu K. Expression of matrix metalloproteinase-9 (MMP-9) in human skin within 1 hour after injury through immunohistochemical staining: a pilot study. Int J Legal Med. 2024.

[385] Sun C, Yan H, Jiang K, Huang L. Protective effect of casticin on experimental skin wound healing of rats. J Surg Res. 2022; 274: 145-152.

[386] Alonso-Nocelo M, Ruiz-Cañas L, Sancho P, et al. Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma. Gut. 2023; 72(2): 345-359.

[387] Chrobok NL, Sestito C, Wilhelmus MM, Drukarch B, van Dam AM. Is monocyte-and macrophage-derived tissue transglutaminase involved in inflammatory processes? Amino Acids. 2017; 49(3): 441-452.

[388] Sun H, Kaartinen MT. Transglutaminases in monocytes and macrophages. Med Sci (Basel). 2018; 6(4): 115.

[389] Kim SY, Nair MG. Macrophages in wound healing: activation and plasticity. Immunol Cell Biol. 2019; 97(3): 258-267.

[390] Xiong Y, Lin Z, Bu P, et al. A whole-course-repair system based on neurogenesis-angiogenesis crosstalk and macrophage reprogramming promotes diabetic wound healing. Adv Mater. 2023; 35(19): e2212300.

[391] Wolf SJ, Melvin WJ, Gallagher K. Macrophage-mediated inflammation in diabetic wound repair. Semin Cell Dev Biol. 2021; 119: 111-118.

[392] Schlundt C, Fischer H, Bucher CH, Rendenbach C, Duda GN, Schmidt-Bleek K. The multifaceted roles of macrophages in bone regeneration: a story of polarization, activation and time. Acta Biomater. 2021; 133: 46-57.

[393] Ross EA, Devitt A, Johnson JR. Macrophages: the good, the bad, and the gluttony. Front Immunol. 2021; 12: 708186.

[394] Miki S, Suzuki JI, Takashima M, Ishida M, Kokubo H, Yoshizumi M. S-1-Propenylcysteine promotes IL-10-induced M2c macrophage polarization through prolonged activation of IL-10R/STAT3 signaling. Sci Rep. 2021; 11(1): 22469.

[395] Selig M, Poehlman L, Lang NC, Völker M, Rolauffs B, Hart ML. Prediction of six macrophage phenotypes and their IL-10 content based on single-cell morphology using artificial intelligence. Front Immunol. 2023; 14: 1336393.

[396] Rahman K, Vengrenyuk Y, Ramsey SA, et al. Inflammatory Ly6Chi monocytes and their conversion to M2 macrophages drive atherosclerosis regression. J Clin Invest. 2017; 127(8): 2904-2915.

[397] Arnold L, Henry A, Poron F, et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med. 2007; 204(5): 1057-1069.

[398] Crane MJ, Daley JM, van Houtte O, Brancato SK, Henry WL, Jr., Albina JE. The monocyte to macrophage transition in the murine sterile wound. PLoS One. 2014; 9(1): e86660.

[399] Cui CY, Ferrucci L, Gorospe M. Macrophage involvement in aging-associated skeletal muscle regeneration. Cells. 2023; 12(9): 1214.

[400] Scala P, Rehak L, Giudice V, et al. Stem cell and macrophage roles in skeletal muscle regenerative medicine. Int J Mol Sci. 2021; 22(19): 10867.

[401] Wang Y, Lu J, Liu Y. Skeletal muscle regeneration in cardiotoxin-induced muscle injury models. Int J Mol Sci. 2022; 23(21): 13380.

[402] Li N, Chen J, Geng C, et al. Myoglobin promotes macrophage polarization to M1 type and pyroptosis via the RIG-I/Caspase1/GSDMD signaling pathway in CS-AKI. Cell Death Discov. 2022; 8(1): 90.

[403] Martins L, Gallo CC, Honda TSB, et al. Skeletal muscle healing by M1-like macrophages produced by transient expression of exogenous GM-CSF. Stem Cell Res Ther. 2020; 11(1): 473.

[404] Tonkin J, Temmerman L, Sampson RD, et al. Monocyte/macrophage-derived IGF-1 orchestrates murine skeletal muscle regeneration and modulates autocrine polarization. Mol Ther. 2015; 23(7): 1189-1200.

[405] Kok HJ, Barton ER. Actions and interactions of IGF-I and MMPs during muscle regeneration. Semin Cell Dev Biol. 2021; 119: 11-22.

[406] Chowdary AR, Maerz T, Henn D, et al. Macrophage-mediated PDGF activation correlates with regenerative outcomes following musculoskeletal trauma. Ann Surg. 2023; 278(2): e349-e359.

[407] Peck BD, Murach KA, Walton RG, et al. A muscle cell-macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading. Faseb J. 2022; 36(2): e22155.

[408] Ratnayake D, Nguyen PD, Rossello FJ, et al. Macrophages provide a transient muscle stem cell niche via NAMPT secretion. Nature. 2021; 591(7849): 281-287.

[409] Shang M, Cappellesso F, Amorim R, et al. Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Nature. 2020; 587(7835): 626-631.

[410] Southerland KW, Xu Y, Peters DT, et al. Skeletal muscle regeneration failure in ischemic-damaged limbs is associated with pro-inflammatory macrophages and premature differentiation of satellite cells. Genome Med. 2023; 15(1): 95.

[411] Tusavitz S, Keoonela S, Kalkstein M, et al. Macrophage-derived Wnt signaling increases endothelial permeability during skeletal muscle injury. Inflamm Res. 2020; 69(12): 1235-1244.

[412] Campana L, Esser H, Huch M, Forbes S. Liver regeneration and inflammation: from fundamental science to clinical applications. Nat Rev Mol Cell Biol. 2021; 22(9): 608-624.

[413] Guilliams M, Scott CL. Liver macrophages in health and disease. Immunity. 2022; 55(9): 1515-1529.

[414] Liu R, Scimeca M, Sun Q, et al. Harnessing metabolism of hepatic macrophages to aid liver regeneration. Cell Death Dis. 2023; 14(8): 574.

[415] Guilliams M, Bonnardel J, Haest B, et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell. 2022; 185(2): 379-396. e38.

[416] Li M, Sun X, Zhao J, et al. CCL5 deficiency promotes liver repair by improving inflammation resolution and liver regeneration through M2 macrophage polarization. Cell Mol Immunol. 2020; 17(7): 753-764.

[417] Li L, Cui L, Lin P, et al. Kupffer-cell-derived IL-6 is repurposed for hepatocyte dedifferentiation via activating progenitor genes from injury-specific enhancers. Cell Stem Cell. 2023; 30(3): 283-299. e9.

[418] Li R, Li D, Nie Y. IL-6/gp130 signaling: a key unlocking regeneration. Cell Regen. 2023; 12(1): 16.

[419] Yang J, Mowry LE, Nejak-Bowen KN, et al. β-Catenin signaling in murine liver zonation and regeneration: a Wnt-Wnt situation! Hepatology. 2014; 60(3): 964-976.

[420] Hu S, Monga SP. Wnt/-catenin signaling and liver regeneration: circuit, biology, and opportunities. Gene Expr. 2021; 20(3): 189-199.

[421] Heo MJ, Suh JH, Poulsen KL, Ju C, Kim KH. Updates on the immune cell basis of hepatic ischemia-reperfusion injury. Mol Cells. 2023; 46(9): 527-534.

[422] Starkey Lewis P, Campana L, Aleksieva N, et al. Alternatively activated macrophages promote resolution of necrosis following acute liver injury. J Hepatol. 2020; 73(2): 349-360.

[423] Du S, Zhang X, Jia Y, et al. Hepatocyte HSPA12A inhibits macrophage chemotaxis and activation to attenuate liver ischemia/reperfusion injury via suppressing glycolysis-mediated HMGB1 lactylation and secretion of hepatocytes. Theranostics. 2023; 13(11): 3856-3871.

[424] Liu Z, Wang M, Wang X, et al. XBP1 deficiency promotes hepatocyte pyroptosis by impairing mitophagy to activate mtDNA-cGAS-STING signaling in macrophages during acute liver injury. Redox Biol. 2022; 52: 102305.

[425] Kim Y, Nurakhayev S, Nurkesh A, Zharkinbekov Z, Saparov A. Macrophage polarization in cardiac tissue repair following myocardial infarction. Int J Mol Sci. 2021; 22(5): 2715.

[426] Yap J, Irei J, Lozano-Gerona J, Vanapruks S, Bishop T, Boisvert WA. Macrophages in cardiac remodelling after myocardial infarction. Nat Rev Cardiol. 2023; 20(6): 373-385.

[427] Peet C, Ivetic A, Bromage DI, Shah AM. Cardiac monocytes and macrophages after myocardial infarction. Cardiovasc Res. 2020; 116(6): 1101-1112.

[428] Chen Y, Wu G, Li M, et al. LDHA-mediated metabolic reprogramming promoted cardiomyocyte proliferation by alleviating ROS and inducing M2 macrophage polarization. Redox Biol. 2022; 56: 102446.

[429] Glinton KE, Ma W, Lantz C, et al. Macrophage-produced VEGFC is induced by efferocytosis to ameliorate cardiac injury and inflammation. J Clin Invest. 2022; 132(9): e140685.

[430] Jian Y, Zhou X, Shan W, et al. Crosstalk between macrophages and cardiac cells after myocardial infarction. Cell Commun Signal. 2023; 21(1): 109.

[431] Thorp EB. Cardiac macrophages and emerging roles for their metabolism after myocardial infarction. J Clin Invest. 2023; 133(18): e171953.

[432] Abe H, Takeda N, Isagawa T, et al. Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. Nat Commun. 2019; 10(1): 2824.

[433] Jiang C, Jin X, Li C, et al. Roles of IL-33 in the pathogenesis of cardiac disorders. Exp Biol Med (Maywood). 2023; 248(22): 2167-2174.

[434] Li Z, Liu X, Zhang X, et al. TRIM21 aggravates cardiac injury after myocardial infarction by promoting M1 macrophage polarization. Front Immunol. 2022; 13: 1053171.

[435] Zha Z, Cheng Y, Cao L, et al. Monomeric CRP aggravates myocardial injury after myocardial infarction by polarizing the macrophage to pro-inflammatory phenotype through JNK signaling pathway. J Inflamm Res. 2021; 14: 7053-7064.

[436] Gurevich DB, Severn CE, Twomey C, et al. Live imaging of wound angiogenesis reveals macrophage orchestrated vessel sprouting and regression. Embo J. 2018; 37(13): e97786.

[437] Hesketh M, Sahin KB, West ZE, Murray RZ. Macrophage phenotypes regulate scar formation and chronic wound healing. Int J Mol Sci. 2017; 18(7): 1545.

[438] Monavarian M, Kader S, Moeinzadeh S, Jabbari E. Regenerative scar-free skin wound healing. Tissue Eng Part B Rev. 2019; 25(4): 294-311.

[439] Hong YK, Chang YH, Lin YC, Chen B, Guevara BEK, Hsu CK. Inflammation in wound healing and pathological scarring. Adv Wound Care (New Rochelle). 2023; 12(5): 288-300.

[440] Ullm F, Riedl P, Machado de Amorim A, et al. 3D scaffold-based macrophage fibroblast coculture model reveals IL-10 dependence of wound resolution phase. Adv Biosyst. 2020; 4(1): e1900220.

[441] Wu R, Zhang H, Zhao M, et al. Nrf2 in keratinocytes protects against skin fibrosis via regulating epidermal lesion and inflammatory response. Biochem Pharmacol. 2020; 174: 113846.

[442] Villarreal-Ponce A, Tiruneh MW, Lee J, et al. Keratinocyte-macrophage crosstalk by the Nrf2/Ccl2/EGF signaling axis orchestrates tissue repair. Cell Rep. 2020; 33(8): 108417.

[443] Sen CK. Human wound and its burden: updated 2022 compendium of estimates. Adv Wound Care (New Rochelle). 2023; 12(12): 657-670.

[444] Wu X, He W, Mu X, et al. Macrophage polarization in diabetic wound healing. Burns Trauma. 2022; 10: 109-116.

[445] Armstrong DG, Tan TW, Boulton AJM, Bus SA. Diabetic foot ulcers: a review. Jama. 2023; 330(1): 62-75.

[446] McDermott K, Fang M, Boulton AJM, Selvin E, Hicks CW. Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers. Diabetes Care. 2023; 46(1): 209-221.

[447] Papachristou S, Pafili K, Papanas N. Skin AGEs and diabetic neuropathy. BMC Endocr Disord. 2021; 21(1): 28.

[448] Harb A, Elbatreek MH, Elshahat A, El-Akabawy N, Barakat W, Elkomy NM. Repurposing alagebrium for diabetic foot ulcer healing: impact on AGEs/NFκB/NOX1 signaling. Eur J Pharmacol. 2023; 959: 176083.

[449] Shomali N, Mahmoudi J, Mahmoodpoor A, et al. Harmful effects of high amounts of glucose on the immune system: an updated review. Biotechnol Appl Biochem. 2021; 68(2): 404-410.

[450] Aki T, Funakoshi T, Noritake K, Unuma K, Uemura K. Extracellular glucose is crucially involved in the fate decision of LPS-stimulated RAW264.7 murine macrophage cells. Sci Rep. 2020; 10(1): 10581.

[451] Kaewarpai T, Thongboonkerd V. High-glucose-induced changes in macrophage secretome: regulation of immune response. Mol Cell Biochem. 2019; 452(1-2): 51-62.

[452] An Y, Zhang H, Wang C, et al. Activation of ROS/MAPKs/NF-κB/NLRP3 and inhibition of efferocytosis in osteoclast-mediated diabetic osteoporosis. Faseb J. 2019; 33(11): 12515-12527.

[453] Mo Y, Mo L, Zhang Y, Zhang Y, Yuan J, Zhang Q. High glucose enhances the activation of NLRP3 inflammasome by ambient fine particulate matter in alveolar macrophages. Part Fibre Toxicol. 2023; 20(1): 41.

[454] He W, Mu X, Wu X, et al. The cGAS-STING pathway: a therapeutic target in diabetes and its complications. Burns Trauma. 2024; 12: tkad050.

[455] Geng K, Ma X, Jiang Z, et al. High glucose-induced STING activation inhibits diabetic wound healing through promoting M1 polarization of macrophages. Cell Death Discov. 2023; 9(1): 136.

[456] Zhao Z, Ming Y, Li X, et al. Hyperglycemia aggravates periodontitis via autophagy impairment and ros-inflammasome-mediated macrophage pyroptosis. Int J Mol Sci. 2023; 24(7): 6309.

[457] Suzuki T, Yamashita S, Hattori K, Matsuda N, Hattori Y. Impact of a long-term high-glucose environment on pro-inflammatory responses in macrophages stimulated with lipopolysaccharide. Naunyn Schmiedebergs Arch Pharmacol. 2021; 394(10): 2129-2139.

[458] Yuan Y, Chen Y, Peng T, et al. Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition. Clin Sci (Lond). 2019; 133(15): 1759-1777.

[459] Twarda-Clapa A, Olczak A, Białkowska AM, Koziołkiewicz M. Advanced glycation end-products (AGEs): formation, chemistry, classification, receptors, and diseases related to AGEs. Cells. 2022; 11(8): 1312.

[460] Shaikh-Kader A, Houreld NN, Rajendran NK, Abrahamse H. The link between advanced glycation end products and apoptosis in delayed wound healing. Cell Biochem Funct. 2019; 37(6): 432-442.

[461] Parthasarathy G, Mauer AS, Golla N, et al. Macrophage RAGE activation is proinflammatory in NASH. JCI Insight. 2024; 9(3): e169138.

[462] Feng Z, Zhu L, Wu J. RAGE signalling in obesity and diabetes: focus on the adipose tissue macrophage. Adipocyte. 2020; 9(1): 563-566.

[463] Leerach N, Munesue S, Harashima A, et al. RAGE signaling antagonist suppresses mouse macrophage foam cell formation. Biochem Biophys Res Commun. 2021; 555: 74-80.

[464] Li K, Chen G, Luo H, et al. MRP8/14 mediates macrophage efferocytosis through RAGE and Gas6/MFG-E8, and induces polarization via TLR4-dependent pathway. J Cell Physiol. 2021; 236(2): 1375-1390.

[465] Fu J, Sun Z, Wang X, et al. The single-cell landscape of kidney immune cells reveals transcriptional heterogeneity in early diabetic kidney disease. Kidney Int. 2022; 102(6): 1291-1304.

[466] Jia Y, Chen J, Zheng Z, et al. Tubular epithelial cell-derived extracellular vesicles induce macrophage glycolysis by stabilizing HIF-1α in diabetic kidney disease. Mol Med. 2022; 28(1): 95.

[467] Codo AC, Davanzo GG, Monteiro LB, et al. Elevated glucose levels favor SARS-CoV-2 infection and monocyte response through a HIF-1α/glycolysis-dependent axis. Cell Metab. 2020; 32(3): 437-446.e5.

[468] Wang Q, Zhong Y, Li Z, et al. Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development. Burns Trauma. 2022; 10: tkac013.

[469] Hull RP, Srivastava PK, D’Souza Z, et al. Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary regulator of oxidative stress and IL-1β synthesis in macrophages. BMC Genomics. 2013; 14: 92.

[470] Kim NY, Kim S, Park HM, et al. Cinnamomum verum extract inhibits NOX2/ROS and PKCδ/JNK/AP-1/NF-κB pathway-mediated inflammatory response in PMA-stimulated THP-1 monocytes. Phytomedicine. 2023; 112: 154685.

[471] Liu J, Wei Y, Jia W, et al. Chenodeoxycholic acid suppresses AML progression through promoting lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway and inhibiting M2 macrophage polarization. Redox Biol. 2022; 56: 102452.

[472] Yang Y, Wang Y, Guo L, Gao W, Tang TL, Yan M. Interaction between macrophages and ferroptosis. Cell Death Dis. 2022; 13(4): 355.

[473] Zhai Z, Gomez-Mejiba SE, Gimenez MS, et al. Free radical-operated proteotoxic stress in macrophages primed with lipopolysaccharide. Free Radic Biol Med. 2012; 53(1): 172-181.

[474] Liu Z, Ma Y, Cui Q, et al. Toll-like receptor 4 plays a key role in advanced glycation end products-induced M1 macrophage polarization. Biochem Biophys Res Commun. 2020; 531(4): 602-608.

[475] Khalid M, Petroianu G, Adem A. Advanced glycation end products and diabetes mellitus: mechanisms and perspectives. Biomolecules. 2022; 12(4): 542.

[476] He S, Hu Q, Xu X, et al. Advanced glycation end products enhance M1 macrophage polarization by activating the MAPK pathway. Biochem Biophys Res Commun. 2020; 525(2): 334-340.

[477] Xing Y, Pan S, Zhu L, et al. Advanced glycation end products induce atherosclerosis via RAGE/TLR4 signaling mediated-m1 macrophage polarization-dependent vascular smooth muscle cell phenotypic conversion. Oxid Med Cell Longev. 2022; 2022: 9763377.

[478] Itakura M, Yamaguchi K, Kitazawa R, et al. Histone functions as a cell-surface receptor for AGEs. Nat Commun. 2022; 13(1): 2974.

[479] Ju CC, Liu XX, Liu LH, et al. Epigenetic modification: a novel insight into diabetic wound healing. Heliyon. 2024; 10(6): e28086.

[480] Mir AR, Habib S, Uddin M. Recent advances in histone glycation: emerging role in diabetes and cancer. Glycobiology. 2021; 31(9): 1072-1079.

[481] Mao QY, He SY, Hu QY, et al. Advanced glycation end products (AGEs) inhibit macrophage efferocytosis of apoptotic β cells through binding to the receptor for AGEs. J Immunol. 2022; 208(5): 1204-1213.

[482] Friggeri A, Banerjee S, Biswas S, et al. Participation of the receptor for advanced glycation end products in efferocytosis. J Immunol. 2011; 186(11): 6191-6198.

[483] Zayed MA, Wei X, Park KM, et al. N-Acetylcysteine accelerates amputation stump healing in the setting of diabetes. Faseb J. 2017; 31(6): 2686-2695.

[484] Afzali H, Jafari Kashi AH, Momen-Heravi M, et al. The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Wound Repair Regen. 2019; 27(3): 277-284.

[485] Saeg F, Orazi R, Bowers GM, Janis JE. Evidence-based nutritional interventions in wound care. Plast Reconstr Surg. 2021; 148(1): 226-238.

[486] Nikolic M, Andjic M, Bradic J, et al. Topical application of siberian pine essential oil formulations enhance diabetic wound healing. Pharmaceutics. 2023; 15(10): 2437.

[487] Eghtedari Y, Oh LJ, Girolamo ND, Watson SL. The role of topical N-acetylcysteine in ocular therapeutics. Surv Ophthalmol. 2022; 67(2): 608-622.

[488] Tian M, Qing C, Niu Y, et al. Effect of aminoguanidine intervention on neutrophils in diabetes inflammatory cells wound healing. Exp Clin Endocrinol Diabetes. 2013; 121(10): 635-642.

[489] Jiang M, Yakupu A, Guan H, et al. Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds. Int Wound J. 2022; 19(1): 52-63.

[490] Chang PC, Tsai SC, Jheng YH, Lin YF, Chen CC. Soft-tissue wound healing by anti-advanced glycation end-products agents. J Dent Res. 2014; 93(4): 388-393.

[491] Kim CH, Kang HY, Kim G, et al. Soluble receptors for advanced glycation end-products prevent unilateral ureteral obstruction-induced renal fibrosis. Front Pharmacol. 2023; 14: 1172269.

[492] Miyagawa T, Iwata Y, Oshima M, et al. Soluble receptor for advanced glycation end products protects from ischemia-and reperfusion-induced acute kidney injury. Biol Open. 2022; 11(1): bio058852.

[493] Malaguarnera L. Influence of resveratrol on the immune response. Nutrients. 2019; 11(5): 946.

[494] Ding Y, Yang P, Li S, Zhang H, Ding X, Tan Q. Resveratrol accelerates wound healing by inducing M2 macrophage polarisation in diabetic mice. Pharm Biol. 2022; 60(1): 2328-2337.

[495] Qing L, Fu J, Wu P, Zhou Z, Yu F, Tang J. Metformin induces the M2 macrophage polarization to accelerate the wound healing via regulating AMPK/mTOR/NLRP3 inflammasome singling pathway. Am J Transl Res. 2019; 11(2): 655-668.

[496] Cavalcante-Silva J, Koh TJ. Targeting the NOD-Like receptor pyrin domain containing 3 inflammasome to improve healing of diabetic wounds. Adv Wound Care (New Rochelle). 2023; 12(11): 644-656.

[497] Tawfeek HM, Abou-Taleb DAE, Badary DM, Ibrahim M, Abdellatif AAH. Pharmaceutical, clinical, and immunohistochemical studies of metformin hydrochloride topical hydrogel for wound healing application. Arch Dermatol Res. 2020; 312(2): 113-121.

[498] Muñoz-Garcia J, Cochonneau D, Télétchéa S, et al. The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis. Theranostics. 2021; 11(4): 1568-1593.

[499] Liu Y, Zhang Z, Wang B, et al. Inflammation-stimulated MSC-derived small extracellular vesicle miR-27b-3p regulates macrophages by targeting CSF-1 to promote temporomandibular joint condylar regeneration. Small. 2022; 18(16): e2107354.

[500] Ead JK, Armstrong DG. Granulocyte-macrophage colony-stimulating factor: conductor of the wound healing orchestra? Int Wound J. 2023; 20(4): 1229-1234.

[501] Freuchet A, Salama A, Remy S, Guillonneau C, Anegon I. IL-34 and CSF-1, deciphering similarities and differences at steady state and in diseases. J Leukoc Biol. 2021; 110(4): 771-796.

[502] Stutchfield BM, Antoine DJ, Mackinnon AC, et al. CSF1 restores innate immunity after liver injury in mice and serum levels indicate outcomes of patients with acute liver failure. Gastroenterology. 2015; 149(7): 1896-1909. e14.

[503] Wei Y, Li J, Huang Y, et al. The clinical effectiveness and safety of using epidermal growth factor, fibroblast growth factor and granulocyte-macrophage colony stimulating factor as therapeutics in acute skin wound healing: a systematic review and meta-analysis. Burns Trauma. 2022; 10: tkac002.

[504] Wang LL, Zhao R, Li JY, et al. Pharmacological activation of cannabinoid 2 receptor attenuates inflammation, fibrogenesis, and promotes re-epithelialization during skin wound healing. Eur J Pharmacol. 2016; 786: 128-136.

[505] Ma C, Ouyang Q, Huang Z, et al. Toll-like receptor 9 inactivation alleviated atherosclerotic progression and inhibited macrophage polarized to M1 phenotype in ApoE-/-mice. Dis Markers. 2015; 2015: 909572.

[506] Schmitt H, Ulmschneider J, Billmeier U, et al. The TLR9 agonist cobitolimod induces IL10-Producing wound healing macrophages and regulatory T cells in ulcerative colitis. J Crohns Colitis. 2020; 14(4): 508-524.

[507] Gao Y, Jin H, Tan H, Cai X, Sun Y. Erythrocyte-derived extracellular vesicles aggravate inflammation by promoting the proinflammatory macrophage phenotype through TLR4-MyD88-NF-κB-MAPK pathway. J Leukoc Biol. 2022; 112(4): 693-706.

[508] Akter S, Sharma RK, Sharma S, Rastogi S, Fiebich BL, Akundi RS. Exogenous ATP modulates PGE(2) release in macrophages through sustained phosphorylation of CDK9 and p38 MAPK. J Leukoc Biol. 2021; 110(4): 663-677.

[509] Gao S, Li L, Li L, et al. Effects of the combination of tanshinone IIA and puerarin on cardiac function and inflammatory response in myocardial ischemia mice. J Mol Cell Cardiol. 2019; 137: 59-70.

[510] Wu J, Ma X, Lu Y, et al. Edible pueraria lobata-derived exosomes promote M2 macrophage polarization. Molecules. 2022; 27(23): 8184.

[511] Luo Z, Qi B, Sun Y, et al. Engineering bioactive M2 macrophage-polarized, anti-inflammatory, miRNA-based liposomes for functional muscle repair: from exosomal mechanisms to biomaterials. Small. 2022; 18(34): e2201957.

[512] Li J, Wei C, Yang Y, Gao Z, Guo Z, Qi F. Apoptotic bodies extracted from adipose mesenchymal stem cells carry microRNA-21-5p to induce M2 polarization of macrophages and augment skin wound healing by targeting KLF6. Burns. 2022; 48(8): 1893-1908.

[513] Zhou LS, Zhao GL, Liu Q, Jiang SC, Wang Y, Zhang DM. Silencing collapsin response mediator protein-2 reprograms macrophage phenotype and improves infarct healing in experimental myocardial infarction model. J Inflamm (Lond). 2015; 12: 11.

[514] Danon D, Madjar J, Edinov E, et al. Treatment of human ulcers by application of macrophages prepared from a blood unit. Exp Gerontol. 1997; 32(6): 633-641.

[515] Lopes TCM, Almeida GG, Souza IA, et al. High-density-immune-complex regulatory macrophages promote recovery of experimental colitis in mice. Inflammation. 2021; 44(3): 1069-1082.

[516] Zheng D, Wang Y, Cao Q, et al. Transfused macrophages ameliorate pancreatic and renal injury in murine diabetes mellitus. Nephron Exp Nephrol. 2011; 118(4): e87-e99.

[517] Theocharidis G, Rahmani S, Lee S, et al. Murine macrophages or their secretome delivered in alginate dressings enhance impaired wound healing in diabetic mice. Biomaterials. 2022; 288: 121692.

[518] Whitaker R, Hernaez-Estrada B, Hernandez RM, Santos-Vizcaino E, Spiller KL. Immunomodulatory biomaterials for tissue repair. Chem Rev. 2021; 121(18): 11305-11335.

[519] Das P, Manna S, Roy S, Nandi SK, Basak P. Polymeric biomaterials-based tissue engineering for wound healing: a systemic review. Burns Trauma. 2023; 11: tkac058.

[520] Fu YJ, Shi YF, Wang LY, et al. All-natural immunomodulatory bioadhesive hydrogel promotes angiogenesis and diabetic wound healing by regulating macrophage heterogeneity. Adv Sci (Weinh). 2023; 10(13): e2206771.

[521] Martin KE, García AJ. Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies. Acta Biomater. 2021; 133: 4-16.

[522] Huang YY, Lin CW, Cheng NC, et al. Effect of a novel macrophage-regulating drug on wound healing in patients with diabetic foot ulcers: a randomized clinical trial. JAMA Netw Open. 2021; 4(9): e2122607.

[523] Wu Y, Zhang J, Lin A, et al. Immunomodulatory poly(L-lactic acid) nanofibrous membranes promote diabetic wound healing by inhibiting inflammation, oxidation and bacterial infection. Burns Trauma. 2024; 12: tkae009.

[524] Huang C, Dong L, Zhao B, et al. Anti-inflammatory hydrogel dressings and skin wound healing. Clin Transl Med. 2022; 12(11): e1094.

[525] Kwak G, Cheng J, Kim H, et al. Sustained exosome-guided macrophage polarization using hydrolytically degradable PEG hydrogels for cutaneous wound healing: identification of key proteins and MiRNAs, and sustained release formulation. Small. 2022; 18(15): e2200060.

[526] Shen P, Chen Y, Luo S, et al. Applications of biomaterials for immunosuppression in tissue repair and regeneration. Acta Biomater. 2021; 126: 31-44.

[527] Huang K, Liu W, Wei W, et al. Photothermal hydrogel encapsulating intelligently bacteria-capturing Bio-MOF for infectious wound healing. ACS Nano. 2022; 16(11): 19491-19508.

[528] Henn D, Chen K, Fehlmann T, et al. Xenogeneic skin transplantation promotes angiogenesis and tissue regeneration through activated Trem2(+) macrophages. Sci Adv. 2021; 7(49): eabi4528.

[529] Tu C, Lu H, Zhou T, et al. Promoting the healing of infected diabetic wound by an anti-bacterial and nano-enzyme-containing hydrogel with inflammation-suppressing, ROS-scavenging, oxygen and nitric oxide-generating properties. Biomaterials. 2022; 286: 121597.

[530] Chen Z, Wang L, Guo C, et al. Vascularized polypeptide hydrogel modulates macrophage polarization for wound healing. Acta Biomater. 2023; 155: 218-234.

[531] Zhao R, Jin X, Li A, et al. Precise diabetic wound therapy: PLS nanospheres eliminate senescent cells via DPP4 targeting and PARP1 activation. Adv Sci (Weinh). 2022; 9(1): e2104128.

[532] Liu W, Zu L, Wang S, et al. Tailored biomedical materials for wound healing. Burns Trauma. 2023; 11: tkad040.

[533] Huang Y, Zhang L, Song R, Mao X, Tang S. A carrageenan/agarose composite sponge and its immunomodulatory activities toward RAW264.7. J Biomed Mater Res A. 2021; 109(6): 829-839.

[534] Yang H, Song L, Sun B, et al. Modulation of macrophages by a paeoniflorin-loaded hyaluronic acid-based hydrogel promotes diabetic wound healing. Mater Today Bio. 2021; 12: 100139.

[535] Wu J, Chen A, Zhou Y, et al. Novel H(2)S-Releasing hydrogel for wound repair via in situ polarization of M2 macrophages. Biomaterials. 2019; 222: 119398.

[536] Saleh B, Dhaliwal HK, Portillo-Lara R, et al. Local immunomodulation using an adhesive hydrogel loaded with miRNA-laden nanoparticles promotes wound healing. Small. 2019; 15(36): e1902232.

[537] Chu D, Chen J, Liu X, et al. A tetramethylpyrazine-loaded hyaluronic acid-based hydrogel modulates macrophage polarization for promoting wound recovery in diabetic mice. Int J Biol Macromol. 2023; 245: 125495.

[538] Deng T, Gao D, Song X, et al. A natural biological adhesive from snail mucus for wound repair. Nat Commun. 2023; 14(1): 396.

[539] Zhou Z, Deng T, Tao M, et al. Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization. Biomaterials. 2023; 299: 122141.

[540] Shen T, Dai K, Yu Y, Wang J, Liu C. Sulfated chitosan rescues dysfunctional macrophages and accelerates wound healing in diabetic mice. Acta Biomater. 2020; 117: 192-203.

[541] Zhang S, Liu Y, Zhang X, et al. Prostaglandin E(2) hydrogel improves cutaneous wound healing via M2 macrophages polarization. Theranostics. 2018; 8(19): 5348-5361.

[542] Sheng W, Qin H, Wang T, et al. Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation. Front Bioeng Biotechnol. 2023; 11: 1199939.

[543] Geng X, Qi Y, Liu X, Shi Y, Li H, Zhao L. A multifunctional antibacterial and self-healing hydrogel laden with bone marrow mesenchymal stem cell-derived exosomes for accelerating diabetic wound healing. Biomater Adv. 2022; 133: 112613.

[544] Kong X, Chen H, Li F, et al. Three-dimension chitosan hydrogel loading melanin composite nanoparticles for wound healing by anti-bacteria, immune activation and macrophage autophagy promotion. Int J Biol Macromol. 2023; 237: 124176.

[545] Vivcharenko V, Wojcik M, Przekora A. Cellular response to vitamin C-enriched chitosan/agarose film with potential application as artificial skin substitute for chronic wound treatment. Cells. 2020; 9(5): 1185.

[546] Chu B, Zhang A, Huang J, et al. Preparation and biological evaluation of a novel agarose-grafting-hyaluronan scaffold for accelerated wound regeneration. Biomed Mater. 2020; 15(4): 045009.

[547] Wojcik M, Kazimierczak P, Vivcharenko V, Koziol M, Przekora A. Effect of vitamin C/hydrocortisone immobilization within curdlan-based wound dressings on in vitro cellular response in context of the management of chronic and burn wounds. Int J Mol Sci. 2021; 22(21): 11474.

[548] Tian M, Zhou L, Fan C, et al. Bimetal-organic framework/GOx-based hydrogel dressings with antibacterial and inflammatory modulation for wound healing. Acta Biomater. 2023; 158: 252-265.

[549] Zhao H, Huang J, Li Y, et al. ROS-scavenging hydrogel to promote healing of bacteria infected diabetic wounds. Biomaterials. 2020; 258: 120286.

[550] Luque GC, Moya M, Picchio ML, et al. Polyphenol iongel patches with antimicrobial, antioxidant and anti-inflammatory properties. Polymers (Basel). 2023; 15(5): 1076.

[551] Liu C, Wang Y, Wang P, et al. In situ electrospun aloe-nanofiber membrane for chronic wound healing. Smart Mater Med. 2023; 4: 514-521.

[552] Qian Y, Zheng Y, Jin J, et al. Immunoregulation in diabetic wound repair with a photoenhanced glycyrrhizic acid hydrogel scaffold. Adv Mater. 2022; 34(29): e2200521.

[553] Wang L, Yu Y, Zhao X, et al. A biocompatible self-powered piezoelectric poly(vinyl alcohol)-based hydrogel for diabetic wound repair. ACS Appl Mater Interfaces. 2022; 14(41): 46273-46289.

[554] Lv H, Zhao M, Li Y, et al. Electrospun chitosan-polyvinyl alcohol nanofiber dressings loaded with bioactive ursolic acid promoting diabetic wound healing. Nanomaterials (Basel). 2022; 12(17): 2933.

[555] Zhu W, Dong Y, Xu P, et al. A composite hydrogel containing resveratrol-laden nanoparticles and platelet-derived extracellular vesicles promotes wound healing in diabetic mice. Acta Biomater. 2022; 154: 212-230.

[556] Zhong G, Qiu M, Zhang J, et al. Fabrication and characterization of PVA@PLA electrospinning nanofibers embedded with Bletilla striata polysaccharide and Rosmarinic acid to promote wound healing. Int J Biol Macromol. 2023; 234: 123693.

[557] Zhu M, Chen YZ, Ou JZ, et al. [Effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice]. Zhonghua Shao Shang Za Zhi. 2022; 38(10): 923-931.

[558] Singh S, Nwabor OF, Sukri DM, et al. Poly (vinyl alcohol) copolymerized with xanthan gum/hypromellose/sodium carboxymethyl cellulose dermal dressings functionalized with biogenic nanostructured materials for antibacterial and wound healing application. Int J Biol Macromol. 2022; 216: 235-250.

[559] Liu W, Zhang Y, Zhu W, et al. Sinomenine inhibits the progression of rheumatoid arthritis by regulating the secretion of inflammatory cytokines and monocyte/macrophage subsets. Front Immunol. 2018; 9: 2228.

[560] Su HY, Yang CY, Ou HT, et al. Cost-effectiveness of novel macrophage-regulating treatment for wound healing in patients with diabetic foot ulcers from the Taiwan health care sector perspective. JAMA Netw Open. 2023; 6(1): e2250639.

[561] Weivoda MM, Chew CK, Monroe DG, et al. Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. Nat Commun. 2020; 11(1): 87.

[562] Maalej KM, Merhi M, Inchakalody VP, et al. CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances. Mol Cancer. 2023; 22(1): 20.

[563] Liu Y, Hu P, Zheng Z, et al. Photoresponsive vaccine-like CAR-M system with high-efficiency central immune regulation for inflammation-related depression. Adv Mater. 2022; 34(11): e2108525.

[564] Chocarro L, Blanco E, Fernández-Rubio L, et al. Cutting-edge CAR engineering: beyond T cells. Biomedicines. 2022; 10(12): 3035.

[565] Usui-Ouchi A, Giles S, Harkins-Perry S, et al. Integrating human iPSC-derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche. Glia. 2023; 71(10): 2372-2382.

[566] Li Y, Che J, Chang L, et al. CD47-and integrin α4/β1-comodified-macrophage-membrane-coated nanoparticles enable delivery of colchicine to atherosclerotic plaque. Adv Healthc Mater. 2022; 11(4): e2101788.

[567] Hou X, Zhang X, Zhao W, et al. Vitamin lipid nanoparticles enable adoptive macrophage transfer for the treatment of multidrug-resistant bacterial sepsis. Nat Nanotechnol. 2020; 15(1): 41-46.

[568] Xu L, Sharkey D, Cantley LG. Tubular GM-CSF promotes late MCP-1/CCR2-mediated fibrosis and inflammation after ischemia/reperfusion injury. J Am Soc Nephrol. 2019; 30(10): 1825-1840.

[569] Bloise N, Rountree I, Polucha C, et al. Engineering immunomodulatory biomaterials for regenerating the infarcted myocardium. Front Bioeng Biotechnol. 2020; 8: 292.

[570] Spangenberg E, Severson PL, Hohsfield LA, et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat Commun. 2019; 10(1): 3758.

[571] Yan D, Liu S, Zhao X, et al. Recombinant human granulocyte macrophage colony stimulating factor in deep second-degree burn wound healing. Medicine (Baltimore). 2017; 96(22): e6881.

[572] Luo B, Sun HT, Wang YT, et al. Clinical efficacy of rhGM-CSF gel and medical collagen sponge on deep second-degree burns of infants: a randomized clinical trial. Medicine (Baltimore). 2024; 103(1): e36304.

[573] Zhang XH, Cui CL, Zhu HY, et al. The effects of recombinant human granulocyte-macrophage colony-stimulating factor gel on third-degree frostbite wounds in northeastern china: a randomized controlled trial. J Burn Care Res. 2023; 44(3): 715-722.

[574] Wu Y, Shen G, Hao C. Negative pressure wound therapy (NPWT) is superior to conventional moist dressings in wound bed preparation for diabetic foot ulcers: A randomized controlled trial. Saudi Med J. 2023; 44(10): 1020-1029.

[575] Wu DC, Kollipara R, Carter MJ, Goldman MP. A novel macrophage-activating gel improves healing and skin quality after CO₂ laser resurfacing of the chest. Dermatol Surg. 2022; 48(12): 1312-1316.

[576] Sanpinit S, Chokpaisarn J, Na-Phatthalung P, et al. Effectiveness of Ya-Samarn-Phlae in diabetic wound healing: evidence from in vitro studies and a multicenter randomized controlled clinical trial. J Ethnopharmacol. 2024; 326: 117929.

[577] Mirastschijski U, Schwab I, Coger V, et al. Lung surfactant accelerates skin wound healing: a translational study with a randomized clinical phase i study. Sci Rep. 2020; 10(1): 2581.

[578] Robinson H, Jarrett P, Vedhara K, et al. The effect of expressive writing on wound healing: Immunohistochemistry analysis of skin tissue two weeks after punch biopsy wounding. J Psychosom Res. 2022; 161: 110987.

[579] Ud-Din S, Foden P, Mazhari M, et al. A double-blind, randomized trial shows the role of zonal priming and direct topical application of epigallocatechin-3-gallate in the modulation of cutaneous scarring in human skin. J Invest Dermatol. 2019; 139(8): 1680-1690. e16.

[580] Ud-Din S, Wilgus TA, McGeorge DD, Bayat A. Pre-emptive priming of human skin improves cutaneous scarring and is superior to immediate and delayed topical anti-scarring treatment post-wounding: a double-blind randomised placebo-controlled clinical trial. Pharmaceutics. 2021; 13(4): 510.

[581] Niebuhr M, Mühlradt PF, Wittmann M, Kapp A, Werfel T. Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2) which accelerates wound healing in mice–a phase I trial in 12 patients. Exp Dermatol. 2008; 17(12): 1052-1056.

RIGHTS & PERMISSIONS

2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.