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As core innate immune effector cells, neutrophils are the central driver of the sterile inflammatory cascade in HIRI. Centered on the Mac-1-Syk core regulatory axis, this review systematically elaborates the neutrophil recruitment cascade and intracellular signaling network in HIRI, focuses on the sequential formation pathways of neutrophil extracellular traps (NETs) and their multi-dimensional injury mechanisms, and dissects the inflammation\u2013thrombosis amplification crosstalk between neutrophils and multiple hepatic non-parenchymal cells. Furthermore, this review clarifies research controversies of core therapeutic targets, analyzes key translational bottlenecks, and proposes a NETs-centered sequential multi-target combination strategy, providing a solid theoretical basis and clear translational direction for the precise targeted therapy of HIRI.<\/jats:p>","DOI":"10.3390\/ijms27114839","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:36:56Z","timestamp":1779892616000},"page":"4839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neutrophils and Neutrophil Extracellular Traps in Hepatic Ischemia\u2013Reperfusion Injury: Molecular Mechanisms and Therapeutic Strategies"],"prefix":"10.3390","volume":"27","author":[{"given":"Furong","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency, The First Affiliated Hospital of Shihezi University, Shihezi 832000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shihezi University, Shihezi 832003, China"},{"name":"Key Laboratory of Xinjiang Phytomedicine Resources and Utilization, Ministry of Education, Shihezi 832003, China"},{"name":"Collaborative Innovation Center for Efficient Production and Resource Utilization of Safflower, Institute for Safflower Industry Research of Shihezi University, Shihezi 832003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"585","DOI":"10.3350\/cmh.2024.0222","article-title":"Current Status and Perspective on Molecular Targets and Therapeutic Intervention Strategy in Hepatic Ischemia-Reperfusion Injury","volume":"30","author":"Liu","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhao, J., Hou, L., Dery, K.J., Yuan, X., Kim, K.H., Kupiec-Weglinski, J.W., Hall, D.R., Thornley, C.J., Hobeika, M.J., and Eltzschig, H.K. (2025). Hepatic Ischemia\u2013Reperfusion Injury: Underlying Mechanisms and Concepts in Liver Surgery and Liver Transplantation. Hepatology.","DOI":"10.1097\/HEP.0000000000001609"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.4110\/in.2018.18.e24","article-title":"Dual Effect of Hepatic Macrophages on Liver Ischemia and Reperfusion Injury during Liver Transplantation","volume":"18","author":"Lu","year":"2018","journal-title":"Immune Netw."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/B978-0-12-394309-5.00006-7","article-title":"Cell Biology of Ischemia\/Reperfusion Injury","volume":"298","author":"Kalogeris","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.4110\/in.2018.18.e27","article-title":"Damage-Associated Molecular Patterns in Inflammatory Diseases","volume":"18","author":"Roh","year":"2018","journal-title":"Immune Netw."},{"key":"ref_6","first-page":"1043","article-title":"Emerging Roles of High-Mobility Group Box-1 in Liver Disease","volume":"12","author":"Wang","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Yazdani, H.O., Handu, S., Popp, B., Geller, D., and Tohme, S. (2022). The Role of Neutrophils as a Driver in Hepatic Ischemia-Reperfusion Injury and Cancer Growth. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.887565"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/labinvest.2017.90","article-title":"Neutrophils: A Cornerstone of Liver Ischemia and Reperfusion Injury","volume":"98","author":"Marques","year":"2018","journal-title":"Lab. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Yazdani, H.O., Morder, K., Geller, D.A., Simmons, R.L., and Tohme, S. (2021). Neutrophil Extracellular Traps Promote T Cell Exhaustion in the Tumor Microenvironment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.785222"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6312","DOI":"10.1038\/s41598-021-85001-2","article-title":"Anti-CD321 Antibody Immunotherapy Protects Liver against Ischemia and Reperfusion-Induced Injury","volume":"11","author":"Yin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41575-018-0020-y","article-title":"Liver Sinusoidal Endothelial Cells-Gatekeepers of Hepatic Immunity","volume":"15","author":"Shetty","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/ar.25673","article-title":"Neutrophil Extracellular Traps Mediate Pathophysiology of Hepatic Cells during Liver Injury","volume":"309","author":"Mak","year":"2026","journal-title":"Anat. Rec."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jhep.2017.09.010","article-title":"IL-33 Exacerbates Liver Sterile Inflammation by Amplifying Neutrophil Extracellular Trap Formation","volume":"68","author":"Yazdani","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1126\/science.aam8897","article-title":"Host DNases Prevent Vascular Occlusion by Neutrophil Extracellular Traps","volume":"358","author":"Rangaswamy","year":"2017","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Cerecedo, D. (2012). Neutrophil Chemotaxis and Polarization: When Asymmetry Means Movement. Hematology-Science and Practice, IntechOpen.","DOI":"10.5772\/34725"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7057","DOI":"10.4049\/jimmunol.1001638","article-title":"LFA-1 and Mac-1 Define Characteristically Different Intralumenal Crawling and Emigration Patterns for Monocytes and Neutrophils in Situ","volume":"185","author":"Sumagin","year":"2010","journal-title":"J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"0212","DOI":"10.34133\/bmr.0212","article-title":"Engineered Macrophage Membrane-Coated Nanoparticles for Hepatic Ischemia\u2013Reperfusion Injury Therapeutics","volume":"29","author":"Yang","year":"2025","journal-title":"Biomater. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"de Oliveira, T.H.C., Marques, P.E., Poosti, F., Ruytinx, P., Amaral, F.A., Brandolini, L., Allegretti, M., Proost, P., and Teixeira, M.M. (2018). Intravital Microscopic Evaluation of the Effects of a CXCR2 Antagonist in a Model of Liver Ischemia Reperfusion Injury in Mice. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01917"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saiman, Y., and Friedman, S.L. (2012). The Role of Chemokines in Acute Liver Injury. Front. Physiol., 3.","DOI":"10.3389\/fphys.2012.00213"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.3748\/wjg.v19.i11.1683","article-title":"Molecular Mechanisms of Liver Ischemia Reperfusion Injury: Insights from Transgenic Knockout Models","volume":"19","author":"Datta","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1177\/1535370213520110","article-title":"Blockade of CXCR2 Signalling: A Potential Therapeutic Target for Preventing Neutrophil-Mediated Inflammatory Diseases","volume":"239","author":"Boppana","year":"2014","journal-title":"Exp. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1002\/ijc.70395","article-title":"The CXCL12\u2013CXCR4\/CXCR7 Axis as a Therapeutic Target in Liver Cancer: Enhancing Immune Evasion and the Future of Combination Therapies","volume":"158","author":"Song","year":"2026","journal-title":"Int. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Castelli, V., Brandolini, L., d\u2019Angelo, M., Giorgio, C., Alfonsetti, M., Cocchiaro, P., Lombardi, F., Cimini, A., and Allegretti, M. (2021). CXCR1\/2 Inhibitor Ladarixin Ameliorates the Insulin Resistance of 3T3-L1 Adipocytes by Inhibiting Inflammation and Improving Insulin Signaling. Cells, 10.","DOI":"10.3390\/cells10092324"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e2407346","DOI":"10.1002\/advs.202407346","article-title":"Hyperglycemia-Enhanced Neutrophil Extracellular Traps Drive Mucosal Immunopathology at the Oral Barrier","volume":"11","author":"Wang","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/HEP.0000000000000207","article-title":"The Evolving Role of Liver Sinusoidal Endothelial Cells in Liver Health and Disease","volume":"78","author":"McConnell","year":"2023","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.yexcr.2017.01.002","article-title":"Neutrophil Adhesion and Crawling Dynamics on Liver Sinusoidal Endothelial Cells under Shear Flow","volume":"351","author":"Yang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"114299","DOI":"10.1016\/j.intimp.2025.114299","article-title":"Liver Ischemia Reperfusion Injury: Mechanisms, Cellular Pathways, and Therapeutic Approaches","volume":"150","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6808","DOI":"10.3748\/wjg.14.6808","article-title":"Failure of P-Selectin Blockade Alone to Protect the Liver from Ischemia-Reperfusion Injury in the Isolated Blood-Perfused Rat Liver","volume":"14","author":"Wyllie","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1111\/eci.12633","article-title":"Cellular Recruitment in Myocardial Ischaemia\/Reperfusion Injury","volume":"46","author":"Bonaventura","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.14336\/AD.2022.0109","article-title":"Targeting the Hepatic Microenvironment to Improve Ischemia\/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments","volume":"13","author":"Gao","year":"2022","journal-title":"Aging Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C409","DOI":"10.1152\/ajpcell.00083.2017","article-title":"Binding of Intercellular Adhesion Molecule 1 to \u03922-Integrin Regulates Distinct Cell Adhesion Processes on Hepatic and Cerebral Endothelium","volume":"315","author":"Tong","year":"2018","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"G577","DOI":"10.1152\/ajpgi.2001.281.2.G577","article-title":"Mac-1 (CD11b\/CD18) and Intercellular Adhesion Molecule-1 in Ischemia-Reperfusion Injury of Rat Liver","volume":"281","author":"Kobayashi","year":"2001","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1007\/s00068-022-02026-6","article-title":"Inflammatory Response to the Ischaemia-Reperfusion Insult in the Liver after Major Tissue Trauma","volume":"48","author":"Li","year":"2022","journal-title":"Eur. J. Trauma Emerg. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.24976\/Discov.Med.202436187.158","article-title":"Simvastatin Inhibits the Formation of NETs by the Mac-1 Pathway to Reduce Hepatic Ischemia-Reperfusion Injury under High-Fat Conditions","volume":"36","author":"Wang","year":"2024","journal-title":"Discov. Med."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fang, J., Ding, H., Huang, J., Liu, W., Hong, T., Yang, J., Wu, Z., Li, Z., Zhang, S., and Liu, P. (2025). Mac-1 Blockade Impedes Adhesion-Dependent Neutrophil Extracellular Trap Formation and Ameliorates Lung Injury in LPS-Induced Sepsis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1548913"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10020-022-00515-3","article-title":"Neutrophil Trogocytosis during Their Trans-Endothelial Migration: Role of Extracellular CIRP","volume":"28","author":"Takizawa","year":"2022","journal-title":"Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kaltenmeier, C., Wang, R., Popp, B., Geller, D., Tohme, S., and Yazdani, H.O. (2022). Role of Immuno-Inflammatory Signals in Liver Ischemia-Reperfusion Injury. Cells, 11.","DOI":"10.3390\/cells11142222"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1091\/mbc.E16-12-0827","article-title":"Ligand-Specific Binding Forces of LFA-1 and Mac-1 in Neutrophil Adhesion and Crawling","volume":"29","author":"Li","year":"2018","journal-title":"Mol. Biol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"168919","DOI":"10.1016\/j.jmb.2024.168919","article-title":"Structural Dynamics of Rho GTPases","volume":"437","author":"Lin","year":"2025","journal-title":"J. Mol. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1182\/blood-2014-02-557843","article-title":"RhoA Determines Disease Progression by Controlling Neutrophil Motility and Restricting Hyperresponsiveness","volume":"123","author":"Jennings","year":"2014","journal-title":"Blood"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1111\/jcmm.14236","article-title":"The Pattern-recognition Molecule Mindin Binds Integrin Mac-1 to Promote Macrophage Phagocytosis via Syk Activation and NF-\u03baB P65 Translocation","volume":"23","author":"Liu","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.1182\/blood-2012-09-457887","article-title":"\u03922 Integrin\u2013Derived Signals Induce Cell Survival and Proliferation of AML Blasts by Activating a Syk\/STAT Signaling Axis","volume":"121","author":"Oellerich","year":"2013","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"a002352","DOI":"10.1101\/cshperspect.a002352","article-title":"Src-Family and Syk Kinases in Activating and Inhibitory Pathways in Innate Immune Cells: Signaling Cross Talk","volume":"3","author":"Lowell","year":"2011","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3748\/wjg.v26.i10.1005","article-title":"Role of Spleen Tyrosine Kinase in Liver Diseases","volume":"26","author":"Kurniawan","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1159\/000446879","article-title":"Spleen Tyrosine Kinase: A Crucial Player and Potential Therapeutic Target in Renal Disease","volume":"133","author":"Ma","year":"2016","journal-title":"Nephron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41420-025-02342-x","article-title":"Syk Inhibitor Attenuates Lupus in Fc\u03b3RIIb-\/- Mice through the Inhibition of DNA Extracellular Traps from Macrophages and Neutrophils via p38MAPK-Dependent Pathway","volume":"11","author":"Charoensappakit","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1186\/s10020-024-00907-7","article-title":"SYK Promotes the Formation of Neutrophil Extracellular Traps by Inducing PKM2 Nuclear Translocation and Promoting STAT3 Phosphorylation to Exacerbate Hepatic Ischemia-Reperfusion Injury and Tumor Recurrence","volume":"30","author":"Chen","year":"2024","journal-title":"Mol. Med."},{"key":"ref_49","first-page":"243","article-title":"The Role of Mitogen-Activated Protein Kinases and the Participation of Intestinal Congestion in Total Hepatic Ischemia-Reperfusion Injury","volume":"53","author":"Kobayashi","year":"2006","journal-title":"Hepatogastroenterology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2147\/JIR.S396604","article-title":"MAPK Signaling Pathways in Hepatic Ischemia\/Reperfusion Injury","volume":"16","author":"Yu","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"290565","DOI":"10.1155\/2013\/290565","article-title":"Pharmacological Inhibition of P38 Mitogen-Activated Protein Kinases Affects KC\/CXCL1-Induced Intraluminal Crawling, Transendothelial Migration, and Chemotaxis of Neutrophils in Vivo","volume":"2013","author":"Xu","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101695","DOI":"10.1016\/j.jcmgh.2025.101695","article-title":"Ubiquitination of Rhomboid 5 Homolog 2 by Constitutive Photomorphogenic 1 Alleviates Hepatic Ischemia-Reperfusion Injury by Regulating the Transforming Growth Factor-\u03b2 Activating Kinase 1-C-Jun N-Terminal Kinase\/P38 Signaling Pathway","volume":"20","author":"Li","year":"2025","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7747","DOI":"10.1038\/s41598-024-58392-1","article-title":"6-Gingerol Attenuates Hepatic Ischemia\/Reperfusion Injury through Regulating MKP5-Mediated P38\/JNK Pathway","volume":"14","author":"Yu","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"113935","DOI":"10.3748\/wjg.v32.i3.113935","article-title":"Targeting Jun N-Terminal Kinase Phosphorylation: A Human-Derived Hepatoprotective Peptide Human Liver Transplantation Peptide 1 Attenuates Hepatic Ischemia-Reperfusion Injury","volume":"32","author":"Xie","year":"2026","journal-title":"World J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.2147\/DDDT.S457130","article-title":"Nepetoidin B Alleviates Liver Ischemia\/Reperfusion Injury via Regulating MKP5 and JNK\/P38 Pathway","volume":"18","author":"Yu","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1042\/CS20201091","article-title":"DUSP12 Acts as a Novel Endogenous Protective Signal against Hepatic Ischemia-Reperfusion Damage by Inhibiting ASK1 Pathway","volume":"135","author":"Boldorini","year":"2021","journal-title":"Clin. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"357","DOI":"10.14218\/JCTH.2023.00339","article-title":"RAMP1 Protects Hepatocytes against Ischemia-Reperfusion Injury by Inhibiting the ERK\/YAP Pathway","volume":"12","author":"Tang","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.7150\/ijms.94177","article-title":"METTL3 Deficiency Aggravates Hepatic Ischemia\/Reperfusion Injury in Mice by Activating the MAPK Signaling Pathway","volume":"21","author":"Gao","year":"2024","journal-title":"Int. J. Med. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4302","DOI":"10.1007\/s10753-025-02327-z","article-title":"Mac-1 Promotes Neutrophil Extracellular Traps Formation via ERK Phosphorylation in Renal Ischemia-Reperfusion Injury","volume":"48","author":"He","year":"2025","journal-title":"Inflammation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10248","DOI":"10.1002\/jcb.28309","article-title":"Crosstalk between Phosphoinositide 3-Kinase\/Akt Signaling Pathway with DNA Damage Response and Oxidative Stress in Cancer","volume":"120","author":"Karimian","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e158199","DOI":"10.1172\/jci.insight.158199","article-title":"PTP1B Inhibitors Protect against Acute Lung Injury and Regulate CXCR4 Signaling in Neutrophils","volume":"7","author":"Song","year":"2022","journal-title":"JCI Insight"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e183237","DOI":"10.1172\/jci.insight.183237","article-title":"PI3Kgamma Promotes Neutrophil Extracellular Trap Formation by Noncanonical Pyroptosis in Abdominal Aortic Aneurysm","volume":"9","author":"Xiong","year":"2024","journal-title":"JCI Insight"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"de Carvalho Oliveira, V., Tatsiy, O., and McDonald, P.P. (2023). Phosphoinositol 3-Kinase-Driven NET Formation Involves Different Isoforms and Signaling Partners Depending on the Stimulus. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1042686"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1954","DOI":"10.4049\/jimmunol.1400478","article-title":"Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via Fc\u03b3RIIIB and Mac-1","volume":"193","author":"Behnen","year":"2014","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.18632\/aging.202246","article-title":"\u03b2-Arrestin-2 Attenuates Hepatic Ischemia-Reperfusion Injury by Activating PI3K\/Akt Signaling","volume":"13","author":"Chen","year":"2020","journal-title":"Aging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-\u03baB in Inflammation and Cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.ejcb.2011.09.008","article-title":"Hepatic Acute Phase Proteins\u2013Regulation by IL-6- and IL-1-Type Cytokines Involving STAT3 and Its Crosstalk with NF-\u03baB-Dependent Signaling","volume":"91","author":"Bode","year":"2012","journal-title":"Eur. J. Cell Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1161\/hh2201.099166","article-title":"Leukocyte Integrin Mac-1 Recruits Toll\/Interleukin-1 Receptor Superfamily Signaling Intermediates to Modulate NF-kappaB Activity","volume":"89","author":"Shi","year":"2001","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrgastro.2010.213","article-title":"NF-\u03baB in the Liver--Linking Injury, Fibrosis and Hepatocellular Carcinoma","volume":"8","author":"Luedde","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3892\/etm.2022.11609","article-title":"Ac2-26 Alleviates Hepatic Ischemia-reperfusion Injury Based on Inhibiting the Positive Feedback Loop of HMGB1\/TLR4\/NF-\u03baB\/Neutrophils","volume":"24","author":"Bai","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3892\/etm.2021.10295","article-title":"Augmenter of Liver Regeneration Ameliorates Ischemia-Reperfusion Injury in Steatotic Liver via Inhibition of the TLR4\/NF-\u03baB Pathway","volume":"22","author":"Weng","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"de Gregorio, E., Colell, A., Morales, A., and Mari, M. (2020). Relevance of SIRT1-NF-\u03baB Axis as Therapeutic Target to Ameliorate Inflammation in Liver Disease. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113858"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"18934","DOI":"10.1074\/jbc.M101103200","article-title":"Akt Stimulates the Transactivation Potential of the RelA\/P65 Subunit of NF-\u03baB through Utilization of the I\u03baB Kinase and Activation of the Mitogen-Activated Protein Kinase P38","volume":"276","author":"Madrid","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4842592","DOI":"10.1155\/2019\/4842592","article-title":"Oleic Acid Protects against Hepatic Ischemia and Reperfusion Injury in Mice by Inhibiting AKT\/mTOR Pathways","volume":"2019","author":"Guo","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Fathi, A.M., Waz, S., Alaaeldin, E., Toni, N.D.M., El-Sheikh, A.A.K., Sayed, A.M., Abdelmohsen, U.R., and Nazmy, M.H. (2023). Blackberry-Loaded AgNPs Attenuate Hepatic Ischemia\/Reperfusion Injury via PI3K\/Akt\/mTOR Pathway. Metabolites, 13.","DOI":"10.3390\/metabo13030419"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"28","DOI":"10.20517\/mtod.2025.03","article-title":"Lipid Metabolism in Liver Transplantation: From Challenge to Chance","volume":"5","author":"Zhang","year":"2025","journal-title":"Metab. Target Organ Damage"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s41065-022-00255-8","article-title":"Integrative Analyses of Genes Related to Liver Ischemia Reperfusion Injury","volume":"159","author":"Wang","year":"2022","journal-title":"Hereditas"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1042\/BST20220271","article-title":"ERK1\/2 in Immune Signalling","volume":"50","author":"Lucas","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"27711","DOI":"10.18632\/oncotarget.8509","article-title":"Repressor and Activator Protein Accelerates Hepatic Ischemia Reperfusion Injury by Promoting Neutrophil Inflammatory Response","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/s41419-022-04955-x","article-title":"Antibiotic Pretreatment Attenuates Liver Ischemia-Reperfusion Injury by Farnesoid X Receptor Activation","volume":"13","author":"Liu","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"739","DOI":"10.2147\/DDDT.S188654","article-title":"Maresin 1 Mitigates Renal Ischemia\/Reperfusion Injury in Mice via Inhibition of the TLR4\/MAPK\/NF-\u03baB Pathways and Activation of the Nrf2 Pathway","volume":"13","author":"Qiu","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1016\/j.bbadis.2017.02.018","article-title":"Knockdown of Sestrin2 Increases Pro-Inflammatory Reactions and ER Stress in the Endothelium via an AMPK Dependent Mechanism","volume":"1863","author":"Hwang","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Ravindran, M., Khan, M.A., and Palaniyar, N. (2019). Neutrophil Extracellular Trap Formation: Physiology, Pathology, and Pharmacology. Biomolecules, 9.","DOI":"10.3390\/biom9080365"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"108461","DOI":"10.1016\/j.clim.2020.108461","article-title":"Hydroxychloroquine Inhibiting Neutrophil Extracellular Trap Formation Alleviates Hepatic Ischemia\/Reperfusion Injury by Blocking TLR9 in Mice","volume":"216","author":"Zhang","year":"2020","journal-title":"Clin. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s40472-019-0230-4","article-title":"The Evolving Role of Neutrophils in Liver Transplant Ischemia-Reperfusion Injury","volume":"6","author":"Nakamura","year":"2019","journal-title":"Curr. Transplant. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Azzouz, D., and Palaniyar, N. (2024). How Do ROS Induce NETosis? Oxidative DNA Damage, DNA Repair, and Chromatin Decondensation. Biomolecules, 14.","DOI":"10.3390\/biom14101307"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Wu, J., Zhang, F., Zheng, X., Zhang, J., Cao, P., Sun, Z., and Wang, W. (2022). Identification of Renal Ischemia Reperfusion Injury Subtypes and Predictive Strategies for Delayed Graft Function and Graft Survival Based on Neutrophil Extracellular Trap-Related Genes. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1047367"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Denning, N.-L., Aziz, M., Gurien, S.D., and Wang, P. (2019). DAMPs and NETs in Sepsis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02536"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.exger.2017.11.018","article-title":"Immunity and Inflammation: From Jekyll to Hyde","volume":"107","author":"Xu","year":"2018","journal-title":"Exp. Gerontol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s00018-022-04126-3","article-title":"Citrullination in the Pathology of Inflammatory and Autoimmune Disorders: Recent Advances and Future Perspectives","volume":"79","author":"Ciesielski","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1055\/s-0040-1715474","article-title":"Netting Liver Disease: Neutrophil Extracellular Traps in the Initiation and Exacerbation of Liver Pathology","volume":"46","author":"Jenne","year":"2020","journal-title":"Semin. Thromb. Hemost."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"107602","DOI":"10.1016\/j.celrep.2020.107602","article-title":"Histones, DNA, and Citrullination Promote Neutrophil Extracellular Trap Inflammation by Regulating the Localization and Activation of TLR4","volume":"31","author":"Tsourouktsoglou","year":"2020","journal-title":"Cell Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.2174\/1570159X21666230308090351","article-title":"Neutrophil Extracellular Traps in Cerebral Ischemia\/Reperfusion Injury:Friend and Foe","volume":"21","author":"Luo","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-024-01933-x","article-title":"Neutrophil Extracellular Traps in Homeostasis and Disease","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Chen, X.-Q., Tu, L., Tang, Q., Zou, J.-S., Yun, X., and Qin, Y.-H. (2023). DNase I Targeted Degradation of Neutrophil Extracellular Traps to Reduce the Damage on IgAV Rat. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291592"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.trsl.2010.02.003","article-title":"Neutrophil Elastase Contributes to the Development of Ischemia\/Reperfusion-Induced Liver Injury by Decreasing the Production of Insulin-like Growth Factor-I in Rats","volume":"155","author":"Kawai","year":"2010","journal-title":"Transl. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"G1116","DOI":"10.1152\/ajpgi.00061.2004","article-title":"Neutrophil Elastase Contributes to the Development of Ischemia-Reperfusion-Induced Liver Injury by Decreasing Endothelial Production of Prostacyclin in Rats","volume":"287","author":"Okajima","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1530\/JME-20-0128","article-title":"NETosis Contributes to the Pathogenesis of Diabetes and Its Complications","volume":"65","author":"Njeim","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/toxsci\/kfq009","article-title":"Mechanisms of Immune-Mediated Liver Injury","volume":"115","author":"Adams","year":"2010","journal-title":"Toxicol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.freeradbiomed.2021.07.007","article-title":"Role of Myeloperoxidase and Oxidant Formation in the Extracellular Environment in Inflammation-Induced Tissue Damage","volume":"172","author":"Hawkins","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"103696","DOI":"10.1016\/j.redox.2025.103696","article-title":"Histones in Neutrophil Extracellular Traps (NETs) Contain Oxidative Post-Translational Modifications Induced by the Myeloperoxidase Oxidant Hypochlorous Acid","volume":"84","author":"Hemmling","year":"2025","journal-title":"Redox Biol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Rensen, S.S., Bieghs, V., Xanthoulea, S., Arfianti, E., Bakker, J.A., Shiri-Sverdlov, R., Hofker, M.H., Greve, J.W., and Buurman, W.A. (2012). Neutrophil-Derived Myeloperoxidase Aggravates Non-Alcoholic Steatohepatitis in Low-Density Lipoprotein Receptor-Deficient Mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052411"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"114934","DOI":"10.1016\/j.intimp.2025.114934","article-title":"Pathological Roles of NETs-Platelet Synergy in Thrombotic Diseases: From Molecular Mechanisms to Therapeutic Targeting","volume":"159","author":"Li","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Sennett, C., and Pula, G. (2025). Trapped in the NETs: Multiple Roles of Platelets in the Vascular Complications Associated with Neutrophil Extracellular Traps. Cells, 14.","DOI":"10.3390\/cells14050335"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"118337","DOI":"10.1016\/j.jep.2024.118337","article-title":"Zixue Powder Attenuates Septic Thrombosis via Reducing Neutrophil Extracellular Trap through Blocking Platelet STING Activation","volume":"331","author":"Zhang","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-Selectin Promotes Neutrophil Extracellular Trap Formation in Mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Ni, X., Wu, X., Zhu, X.-X., Li, J.-H., Yin, X.-Y., and Lu, L. (2022). Carabin Deficiency Aggravates Hepatic Ischemia-Reperfusion Injury Through Promoting Neutrophil Trafficking via Ras and Calcineurin Signaling. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.773291"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"155923","DOI":"10.1016\/j.phymed.2024.155923","article-title":"Radix Rehmanniae Praeparata Extracts Ameliorate Hepatic Ischemia-Reperfusion Injury by Reversing LRP1-NOTCH1-C\/EBP\u03b2 Axis-Mediated Senescence Fate of LSECs","volume":"133","author":"Zhang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s11427-019-1596-4","article-title":"Endothelial Notch Activation Promotes Neutrophil Transmigration via Downregulating Endomucin to Aggravate Hepatic Ischemia\/Reperfusion Injury","volume":"63","author":"Zhang","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Yan, J., Huang, A., Zhang, S., Yao, N., Huang, J., Jiang, Z., Wang, J., Chen, F., Yu, Q., and Cheng, J. (2025). CD177+ Neutrophils Drive Extracellular Matrix Remodelling and HGF-Alpha Release in ALPPS-Induced Liver Regeneration. Gut.","DOI":"10.1136\/gutjnl-2025-336300"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.jhep.2024.12.003","article-title":"Zonal Control of Liver Inflammation Is Orchestrated by Periportal Kupffer Cells","volume":"82","author":"Ramachandran","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1097\/HEP.0000000000000590","article-title":"Single-Cell Immune Profiling of Mouse Liver Aging Reveals Cxcl2+ Macrophages Recruit Neutrophils to Aggravate Liver Injury","volume":"79","author":"Liu","year":"2024","journal-title":"Hepatology"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Roushansarai, N.S., Pascher, A., and Becker, F. (2022). Innate Immune Cells during Machine Perfusion of Liver Grafts-The Janus Face of Hepatic Macrophages. J. Clin. Med., 11.","DOI":"10.3390\/jcm11226669"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/hep.31680","article-title":"Two Faces of Neutrophils in Liver Disease Development and Progression","volume":"74","author":"Cho","year":"2021","journal-title":"Hepatology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"117220","DOI":"10.1016\/j.bcp.2025.117220","article-title":"Agomir-223 Treatment after Lung Blast Injury Reduces the Inflammatory Response by Regulating the NLRP3 Inflammasome to Inhibit M1 Macrophage Function","volume":"242","author":"Lu","year":"2025","journal-title":"Biochem. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Yu, W., Wang, S., Wang, Y., Chen, H., Nie, H., Liu, L., Zou, X., Gong, Q., and Zheng, B. (2023). MicroRNA: Role in Macrophage Polarization and the Pathogenesis of the Liver Fibrosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1147710"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"104093","DOI":"10.1016\/j.redox.2026.104093","article-title":"PP4 Modulates Macrophage-Neutrophil Crosstalk to Restrict CCL5-Driven NETosis in Sepsis","volume":"91","author":"Yang","year":"2026","journal-title":"Redox Biol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"8936","DOI":"10.1021\/acsnano.6c02254","article-title":"Charge-Adaptive Nanoparticle Attenuates Inflammation via Targeting Neutrophil Extracellular Traps (NETs) and Breaking NETs-Macrophage Crosstalk","volume":"20","author":"Chen","year":"2026","journal-title":"ACS Nano"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e70063","DOI":"10.1002\/mco2.70063","article-title":"Neutrophil Heterogeneity and Plasticity: Unveiling the Multifaceted Roles in Health and Disease","volume":"6","author":"He","year":"2025","journal-title":"MedComm"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2411880","DOI":"10.1002\/advs.202411880","article-title":"Hypoxia Microenvironment Preconditioning Attenuated Myocardial Ischemia-Reperfusion Injury via Stc1-Mediating Cardiomyocyte Self-Protection and Neutrophil Polarization","volume":"12","author":"Huang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4103\/NRR.NRR-D-23-01336","article-title":"Cell Polarization in Ischemic Stroke: Molecular Mechanisms and Advances","volume":"20","author":"Li","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Deng, Y., Zhao, Z., Sheldon, M., Zhao, Y., Teng, H., Martinez, C., Zhang, J., Lin, C., Sun, Y., and Yao, F. (2023). LIFR Recruits HGF-Producing Neutrophils to Promote Liver Injury Repair and Regeneration. bioRxiv.","DOI":"10.1101\/2023.03.18.533289"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1002\/hep.1840170523","article-title":"Functional Inactivation of Neutrophils with a Mac-1 (CD11b\/CD18) Monoclonal Antibody Protects against Ischemia-Reperfusion Injury in Rat Liver","volume":"17","author":"Jaeschke","year":"1993","journal-title":"Hepatology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S1499-3872(15)60348-4","article-title":"Pentoxifylline Enhances the Protective Effects of Hypertonic Saline Solution on Liver Ischemia Reperfusion Injury through Inhibition of Oxidative Stress","volume":"14","author":"Figueira","year":"2015","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41467-018-02896-8","article-title":"A Ligand-Specific Blockade of the Integrin Mac-1 Selectively Targets Pathologic Inflammation While Maintaining Protective Host-Defense","volume":"9","author":"Wolf","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"6650301","DOI":"10.1155\/mi\/6650301","article-title":"Neutrophils in Intracerebral Hemorrhage: Roles, Mechanisms, and Therapeutic Implications","volume":"2025","author":"Chu","year":"2025","journal-title":"Mediat. Inflamm."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1084\/jem.160.6.1901","article-title":"Inherited Deficiency of the Mac-1, LFA-1, P150,95 Glycoprotein Family and Its Molecular Basis","volume":"160","author":"Springer","year":"1984","journal-title":"J. Exp. Med."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Nojima, H., Konishi, T., Freeman, C.M., Schuster, R.M., Japtok, L., Kleuser, B., Edwards, M.J., Gulbins, E., and Lentsch, A.B. (2016). Chemokine Receptors, CXCR1 and CXCR2, Differentially Regulate Exosome Release in Hepatocytes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0161443"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Zarbock, A., and Stadtmann, A. (2012). CXCR2: From Bench to Bedside. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00263"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1002\/cncr.35489","article-title":"Clinical Outcomes of Ruxolitinib Treatment in 595 Intermediate-1 Risk Patients with Myelofibrosis: The RUX-MF Real-World Study","volume":"130","author":"Palandri","year":"2024","journal-title":"Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41588-021-00837-8","article-title":"The Sickening Consequences of Too Much SYK Signaling","volume":"53","author":"Aksentijevich","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41401-023-01166-8","article-title":"Development of PI3K\u03b3 Selective Inhibitors: The Strategies and Application","volume":"45","author":"Gu","year":"2024","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Zheng, X., Wu, X., Wen, Q., Tang, H., Zhao, L., Shi, F., Li, Y., Yin, Z., Zou, Y., and Song, X. (2023). Eriodictyol Alleviated LPS\/D-GalN-Induced Acute Liver Injury by Inhibiting Oxidative Stress and Cell Apoptosis via PI3K\/AKT Signaling Pathway. Nutrients, 15.","DOI":"10.3390\/nu15204349"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Shaker, M.E., Gomaa, H.A.M., Hazem, S.H., Abdelgawad, M.A., El-Mesery, M., and Shaaban, A.A. (2023). Mitigation of Acetaminophen-Induced Liver Toxicity by the Novel Phosphatidylinositol 3-Kinase Inhibitor Alpelisib. Front. Pharmacol., 14, Erratum in Front. Pharmacol. 2023, 14, 1281416. https:\/\/doi.org\/10.3389\/fphar.2023.1281416.","DOI":"10.3389\/fphar.2023.1281416"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Wang, G., Zhang, C., Kambara, H., Dambrot, C., Xie, X., Zhao, L., Xu, R., Oneglia, A., Liu, F., and Luo, H.R. (2022). Identification of the Transgene Integration Site and Host Genome Changes in MRP8-Cre\/Ires-EGFP Transgenic Mice by Targeted Locus Amplification. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.875991"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1631\/jzus.B1200042","article-title":"Conditional Gene Manipulation: Cre-Ating a New Biological Era","volume":"13","author":"Zhang","year":"2012","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"qiae160","DOI":"10.1093\/jleuko\/qiae160","article-title":"Effect on Neutrophil Migration and Antimicrobial Functions by the Bruton\u2019s Tyrosine Kinase Inhibitors Tolebrutinib, Evobrutinib, and Fenebrutinib","volume":"117","author":"Renders","year":"2025","journal-title":"J. Leukoc. Biol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13054-025-05283-0","article-title":"\u201cThe NET Effect\u201d: Neutrophil Extracellular Traps\u2014A Potential Key Component of the Dysregulated Host Immune Response in Sepsis","volume":"29","author":"Retter","year":"2025","journal-title":"Crit. Care"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Yun, H., Chi, Y., Wei, B., Bai, H., Cao, W., Zhang, Z., Zhang, Y., Zhang, Q., and Duan, H. (2025). Cl-Amidine Confers Organ Protection and Improves Survival in Hemorrhagic Shock Rats via the PAD4-CitH3-NETs Axis. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0327085"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1002\/hep.27841","article-title":"Damage-associated Molecular Pattern\u2013Activated Neutrophil Extracellular Trap Exacerbates Sterile Inflammatory Liver Injury","volume":"62","author":"Huang","year":"2015","journal-title":"Hepatology"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Jia, Y., Jia, R., Taledaohan, A., Wang, Y., and Wang, Y. (2024). Structure\u2013Activity Relationship of PAD4 Inhibitors and Their Role in Tumor Immunotherapy. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16030335"},{"key":"ref_143","first-page":"2652","article-title":"Targeted Delivery of Protein Arginine Deiminase-4 Inhibitors to Limit Arterial Intimal NETosis and Preserve Endothelial Integrity","volume":"117","author":"Molinaro","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Chen, F., Nam, Q., Wang, L.D., Chammas, F., Wuestefeld, T., Lee, B.T.K., and Wong, S.L. (2025). Tirzepatide Reduces Diet-Induced Senescence and NETosis-Mediated Liver Fibrosis in Mice. bioRxiv.","DOI":"10.1101\/2025.05.27.656284"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"150145","DOI":"10.1016\/j.ijbiomac.2026.150145","article-title":"Therapeutic Potential of a Long-Acting Form of rhDNase I for the Treatment of Cystic Fibrosis","volume":"340","author":"Grigoletto","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Li, L., Tan, Q., Wu, X., Mou, X., Lin, Z., Liu, T., Huang, W., Deng, L., Jin, T., and Xia, Q. (2024). Coagulopathy and Acute Pancreatitis: Pathophysiology and Clinical Treatment. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1477160"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Liu, Y., Yan, P., Bin, Y., Qin, X., and Wu, Z. (2022). Neutrophil Extracellular Traps and Complications of Liver Transplantation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1054753"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"rqad013","DOI":"10.1093\/rpsppr\/rqad013","article-title":"LP342, a Novel Histone Deacetylase Inhibitor, Decreases Nitro-Oxidative Stress, Mitochondrial Dysfunction and Hepatic Ischaemia\/Reperfusion Injury in Mice","volume":"2","author":"Samuvel","year":"2023","journal-title":"RPS Pharm. Pharmacol. Rep."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s10620-013-2963-8","article-title":"Sivelestat Sodium Hydrate Inhibits Neutrophil Migration to the Vessel Wall and Suppresses Hepatic Ischemia\u2013Reperfusion Injury","volume":"59","author":"Sakai","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2147\/JIR.S396049","article-title":"DNase I and Sivelestat Ameliorate Experimental Hindlimb Ischemia-Reperfusion Injury by Eliminating Neutrophil Extracellular Traps","volume":"16","author":"Wang","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"111700","DOI":"10.1016\/j.msec.2020.111700","article-title":"Sivelestat-Loaded Nanostructured Lipid Carriers Modulate Oxidative and Inflammatory Stress in Human Dental Pulp and Mesenchymal Stem Cells Subjected to Oxygen-Glucose Deprivation","volume":"120","author":"Prakash","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.2147\/DDDT.S480148","article-title":"Sivelestat Sodium Alleviates Ischemia-Reperfusion-Induced Acute Kidney Injury via Suppressing TLR4\/Myd88\/NF-\u03baB Signaling Pathway in Mice","volume":"18","author":"Wang","year":"2024","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2002499","DOI":"10.1002\/advs.202002499","article-title":"Chemically Engineered Immune Cell-Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools","volume":"8","author":"Jahromi","year":"2021","journal-title":"Adv. Sci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1084\/jem.20042614","article-title":"The Nuclear Factor HMGB1 Mediates Hepatic Injury after Murine Liver Ischemia-Reperfusion","volume":"201","author":"Tsung","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12951-025-03195-3","article-title":"Innovative Nanoparticle-Based Approaches for Modulating Neutrophil Extracellular Traps in Diseases: From Mechanisms to Therapeutics","volume":"23","author":"Li","year":"2025","journal-title":"J. Nanobiotechnol"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"102226","DOI":"10.1016\/j.mtbio.2025.102226","article-title":"CD11b-Modified ROS\/pH-Responsive Nanoparticles Co-Deliver Dioscin and siRNA to Improve Cardiac Repair after Myocardial Infarction by Reducing Neutrophil Recruitment","volume":"34","author":"Xu","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Algariri, E.S., Nordin, F., Ng, M.H., Mohd Idris, I., Abdul Karim, N., Tye, G.J., and Wan Kamarul Zaman, W.S. (2026). Mesenchymal Stromal Cells and Extracellular Vesicles: A Novel Therapeutic Paradigm for Mitochondrial Dysfunctions. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041981"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"121486","DOI":"10.1016\/j.biomaterials.2022.121486","article-title":"Extracellular Vesicles Derived from Mesenchymal Stromal Cells as Nanotherapeutics for Liver Ischaemia\u2013Reperfusion Injury by Transferring Mitochondria to Modulate the Formation of Neutrophil Extracellular Traps","volume":"284","author":"Lu","year":"2022","journal-title":"Biomaterials"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/imr.13154","article-title":"Human Neutrophils \u2260 Murine Neutrophils: Does It Matter?","volume":"314","author":"Nauseef","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2147\/DMSO.S408170","article-title":"Translation Animal Models of Diabetic Kidney Disease: Biochemical and Histological Phenotypes, Advantages and Limitations","volume":"16","author":"Luo","year":"2023","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nri2972","article-title":"Overcoming Hurdles in Developing Successful Drugs Targeting Chemokine Receptors","volume":"11","author":"Schall","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3892\/br.2025.1927","article-title":"Remote Ischemic Conditioning in Experimental Hepatic Ischemia-reperfusion: A Systematic Review and Meta-analysis","volume":"22","author":"Tian","year":"2025","journal-title":"Biomed. Rep."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S1470-2045(22)00187-5","article-title":"Efficacy in Randomised Trials: The Time Matters","volume":"23","author":"Ottaiano","year":"2022","journal-title":"Lancet Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:31:02Z","timestamp":1780399862000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/4839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,27]]},"references-count":163,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27114839"],"URL":"https:\/\/doi.org\/10.3390\/ijms27114839","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,27]]}}}