{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:48Z","timestamp":1786121388820,"version":"build-2736575974"},"reference-count":76,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82474151"],"award-info":[{"award-number":["82474151"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82474151"],"award-info":[{"award-number":["82474151"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Discipline Construction Project of Hunan University of Chinese Medicine","award":["Z2023JBGS05"],"award-info":[{"award-number":["Z2023JBGS05"]}]},{"DOI":"10.13039\/100009377","name":"Education Department of Hunan Province","doi-asserted-by":"crossref","award":["23A0293"],"award-info":[{"award-number":["23A0293"]}],"id":[{"id":"10.13039\/100009377","id-type":"DOI","asserted-by":"crossref"}]},{"award":["23A0293"],"award-info":[{"award-number":["23A0293"]}],"id":[{"id":"https:\/\/ror.org\/05ckg3w11","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["2025JJ80091"],"award-info":[{"award-number":["2025JJ80091"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hunan Provincial Graduate Research and Innovation Project","award":["CX20251203"],"award-info":[{"award-number":["CX20251203"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Increased S100 calcium-binding protein A9 (S100A9)-related signals have been reported in selected hepatic and ocular inflammatory settings. This structured narrative review evaluates S100A9-related species as candidate participants in hepato\u2013ocular crosstalk. Across human, ocular fluid, animal, and cellular studies, the available findings provide context-specific support for disease-associated hepatic expression and ocular responsiveness, with stronger evidence for selected local S100A9\u2013Toll-like receptor 4 (TLR4)-associated effects than for S100A9-specific receptor for advanced glycation end products (RAGE) signaling. Clinical associations involving metabolic dysfunction-associated steatotic liver disease, diabetic retinopathy, chronic liver disease, dry eye disease, and uveitis are heterogeneous and confounded. Interpretation is further limited by the non-equivalence of S100A9, S100A8\/A9, calprotectin, and higher-order complexes. Current evidence, therefore, suggests that S100A9-related species may serve as exploratory indicators of inflammatory activity or contribute to local inflammatory amplification in selected settings, rather than acting as established liver-derived causal signals. Future studies should prioritize analyte-specific measurement, source tracing, and selective perturbation. S100A9 is best regarded as a testable candidate node within a broader metabolic\u2013inflammatory network.<\/jats:p>","DOI":"10.3390\/biology15151306","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:41:42Z","timestamp":1785926502000},"page":"1306","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S100A9 as a Candidate Molecular Bridge in Hepato\u2013Ocular Crosstalk"],"prefix":"10.3390","volume":"15","author":[{"given":"Peng","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4609-501X","authenticated-orcid":false,"given":"Yamei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0570-2995","authenticated-orcid":false,"given":"Bohou","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhui","family":"Tuo","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-1797","authenticated-orcid":false,"given":"Limei","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8916-0523","authenticated-orcid":false,"given":"Qiuxian","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gao, S., Leung, M., Radhakrishnan, R., and Lobo, G.P. (2026). The Liver-Eye Axis of Dietary Vitamin A Homeostasis: A Review of Mechanisms, Receptors, and Visual Outcomes. Nutrients, 18.","DOI":"10.3390\/nu18050803"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"528","DOI":"10.5935\/0004-2749.20220099","article-title":"Ophthalmological manifestations of hereditary transthyretin amyloidosis","volume":"85","author":"Gondim","year":"2022","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kitahara, J., Yoshinaga, T., Kakihara, S., Hirano, T., Imai, A., Miyahara, T., Yazaki, M., Sekijima, Y., and Murata, T. (2023). Ocular findings in patients with acquired ATTRv amyloidosis following domino liver transplantation. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291716"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.eprac.2021.02.004","article-title":"Association Between Non-Alcoholic Fatty Liver Disease and Diabetes-Related Microvascular Complications: A Retrospective Cross-Sectional Study of Hospitalized Patients","volume":"28","author":"Wen","year":"2022","journal-title":"Endocr. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/jdi.13489","article-title":"Association of non-alcoholic fatty liver disease with diabetic retinopathy in type 2 diabetic patients: A meta-analysis of observational studies","volume":"12","author":"Song","year":"2021","journal-title":"J. Diabetes Investig."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liu, L., You, Q., Yu, W., Lett, A.M., Wu, Y., Zeng, J., Fan, M., Chen, B., Fu, W., and Xu, S. (2025). Association between steatotic liver disease and microvascular complications in individuals with type 2 diabetes: A cohort study in the UK Biobank. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1554798"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Bergram, M., Kechagias, S., Iredahl, F., Balkhed, W., Holmberg, M., Dahlstr\u00f6m, N., Lundberg, P., Nasr, P., Ekstedt, M., and R\u00e5dholm, K. (2025). Microvascular complications of type 2 diabetes with or without MASLD: The EPSOMIP study, a primary care cohort study. BMC Prim. Care, 26.","DOI":"10.1186\/s12875-025-03096-2"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1007\/s40123-023-00747-4","article-title":"Evaluation of the Clinical Characteristics of Dry Eye Secondary to Different Types of Liver Diseases","volume":"12","author":"Li","year":"2023","journal-title":"Ophthalmol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13098-025-01584-0","article-title":"Association of socioeconomic status with diabetic microvascular complications: A UK Biobank prospective cohort study","volume":"17","author":"Huang","year":"2025","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110131","DOI":"10.1016\/j.exer.2024.110131","article-title":"Paquinimod attenuates retinal injuries by suppressing the S100A9\/TLR4 signaling in an experimental model of diabetic retinopathy","volume":"249","author":"Deng","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110052","DOI":"10.1016\/j.exer.2024.110052","article-title":"S100A9-TLR4 axis aggravates dry eye through the blockage of autophagy","volume":"247","author":"Liang","year":"2024","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1167\/iovs.66.1.35","article-title":"S100A8\/A9 Promotes Dendritic Cell-Mediated Th17 Cell Response in Sj\u00f6gren\u2019s Dry Eye Disease by Regulating the Acod1\/STAT3 Pathway","volume":"66","author":"Wei","year":"2025","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.exer.2006.09.016","article-title":"S100A9-Positive Granulocytes and Monocytes in Lipopolysaccharide-Induced Anterior Ocular Inflammation","volume":"84","author":"Chi","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1097\/HEP.0000000000000520","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"78","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1136\/gutjnl-2021-324855","article-title":"Calprotectin: From biomarker to biological function","volume":"70","author":"Jukic","year":"2021","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.1038\/s41467-024-52829-x","article-title":"Postnatal supplementation with alarmins S100a8\/a9 ameliorates malnutrition-induced neonate enteropathy in mice","volume":"15","author":"Perruzza","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Inciarte-Mundo, J., Frade-Sosa, B., and Sanmart\u00ed, R. (2022). From bench to bedside: Calprotectin (S100A8\/S100A9) as a biomarker in rheumatoid arthritis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1001025"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, S., Song, R., Wang, Z., Jing, Z., Wang, S., and Ma, J. (2018). S100A8\/A9 in Inflammation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01298"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1016\/j.apsb.2023.07.027","article-title":"MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis","volume":"13","author":"Hou","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Wu, F., Teng, F., Guo, S., and Li, H. (2023). Deficiency of S100A9 Alleviates Sepsis-Induced Acute Liver Injury through Regulating AKT-AMPK-Dependent Mitochondrial Energy Metabolism. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032112"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00109-024-02469-x","article-title":"Neutrophil-secreted S100A8\/A9 participates in fatty liver injury and fibrosis by promoting myofibroblast migration","volume":"102","author":"Chang","year":"2024","journal-title":"J. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e190635","DOI":"10.1172\/JCI190635","article-title":"Adipocyte death promotes hepatic infiltration of S100A8+ macrophages and steatotic liver disease progression in mice","volume":"135","author":"Guan","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1038\/s41590-025-02255-y","article-title":"Single-cell atlas of human liver and blood immune cells across fatty liver disease stages reveals distinct signatures linked to liver dysfunction and fibrogenesis","volume":"26","author":"Martin","year":"2025","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jcmgh.2021.08.002","article-title":"E-Selectin-Dependent Inflammation and Lipolysis in Adipose Tissue Exacerbate Steatosis-to-NASH Progression via S100A8\/9","volume":"13","author":"Rodrigues","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_25","first-page":"110","article-title":"Portulaca oleracea alleviates CCl4-induced acute liver injury by regulating hepatic S100A8 and S100A9","volume":"15","author":"Qian","year":"2022","journal-title":"Chin. Herb. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1097\/SHK.0000000000002470","article-title":"Targeting S100A9-TLR2 Axis Controls Macrophage NLRP3 Inflammasome Activation in Fatty Liver Ischemia Reperfusion Injury","volume":"63","author":"Sheng","year":"2025","journal-title":"Shock"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"150624","DOI":"10.1016\/j.ijbiomac.2026.150624","article-title":"Macrophage-derived S100A9 drives liver fibrosis in Echinococcus multilocularis infection by up-regulating secreted protein acidic and rich in cysteine (SPARC) in hepatic stellate cells","volume":"346","author":"Yang","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Garcia, V., Perera, Y.R., and Chazin, W.J. (2022). A Structural Perspective on Calprotectin as a Ligand of Receptors Mediating Inflammation and Potential Drug Target. Biomolecules, 12.","DOI":"10.3390\/biom12040519"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1111\/febs.14775","article-title":"A subset of calcium-binding S100 proteins show preferential heterodimerization","volume":"286","author":"Spratt","year":"2019","journal-title":"FEBS J."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Schenten, V., Plan\u00e7on, S., Jung, N., Hann, J., Bueb, J.L., Br\u00e9chard, S., Tschirhart, E.J., and Tolle, F. (2018). Secretion of the Phosphorylated Form of S100A9 from Neutrophils Is Essential for the Proinflammatory Functions of Extracellular S100A8\/A9. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00447"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s12931-025-03181-1","article-title":"Extracellular vesicle-bound S100A8\/A9 is differentially expressed in septic shock and prompts acute lung injury","volume":"26","author":"Wang","year":"2025","journal-title":"Respir. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cca.2021.02.022","article-title":"Circulating calprotectin as biomarker in neutrophil-related inflammation: Pre-analytical recommendations and reference values according to sample type","volume":"517","author":"Mylemans","year":"2021","journal-title":"Clin. Chim. Acta"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"108557","DOI":"10.1016\/j.exer.2021.108557","article-title":"Loss of TLR4 in endothelial cells but not M\u00fcller cells protects the diabetic retina","volume":"206","author":"Seidel","year":"2021","journal-title":"Exp. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1007\/s00125-010-1900-z","article-title":"Hyperglycaemia-induced pro-inflammatory responses by retinal M\u00fcller glia are regulated by the receptor for advanced glycation end-products (RAGE)","volume":"53","author":"Zong","year":"2010","journal-title":"Diabetologia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"973","DOI":"10.2337\/db22-0761","article-title":"Subendothelial Matrix Stiffening by Lysyl Oxidase Enhances RAGE-Mediated Retinal Endothelial Activation in Diabetes","volume":"72","author":"Chandrakumar","year":"2023","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1080\/15548627.2021.1926655","article-title":"HMGB1 downregulation in retinal pigment epithelial cells protects against diabetic retinopathy through the autophagy\u2013lysosome pathway","volume":"18","author":"Feng","year":"2022","journal-title":"Autophagy"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Portillo, J.-A.C., Pfaff, A., Vos, S., Weng, M., Nagaraj, R.H., and Subauste, C.S. (2024). Advanced glycation end products upregulate CD40 in human retinal endothelial and M\u00fcller cells: Relevance to diabetic retinopathy. Cells, 13.","DOI":"10.3390\/cells13050429"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. Integr. Peer Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","article-title":"Liver sinusoidal endothelial cells: Physiology and role in liver diseases","volume":"66","author":"Poisson","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jaci.2023.01.037","article-title":"Complex regulation of alarmins S100A8\/A9 and secretion via gasdermin D pores exacerbates autoinflammation in familial Mediterranean fever","volume":"152","author":"Jorch","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sprenkeler, E.G.G., Zandstra, J., van Kleef, N.D., Goetschalckx, I., Verstegen, B., Aarts, C.E.M., Janssen, H., Tool, A.T.J., van Mierlo, G., and van Bruggen, R. (2022). S100A8\/A9 Is a Marker for the Release of Neutrophil Extracellular Traps and Induces Neutrophil Activation. Cells, 11.","DOI":"10.3390\/cells11020236"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"646","DOI":"10.3892\/etm.2022.11583","article-title":"S100A9-containing serum exosomes obtained from patients with burn injuries promote myocardial cell pyroptosis through NLRP3","volume":"24","author":"Wang","year":"2022","journal-title":"Exp. Ther. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1038\/s41590-023-01656-1","article-title":"E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8\/S100A9 release from neutrophils via transient gasdermin D pore formation","volume":"24","author":"Pruenster","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, Y., Kong, X., You, Y., Xiang, L., Zhang, Y., Wu, R., Zhou, L., and Duan, L. (2022). S100A8-Mediated NLRP3 Inflammasome-Dependent Pyroptosis in Macrophages Facilitates Liver Fibrosis Progression. Cells, 11.","DOI":"10.3390\/cells11223579"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e14111","DOI":"10.1111\/eci.14111","article-title":"Systematic review of the role of calprotectin in cirrhosis","volume":"54","author":"Fortuny","year":"2024","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1016\/j.dsx.2019.03.014","article-title":"Correlation between systemic S100A8 and S100A9 levels and severity of diabetic retinopathy in patients with type 2 diabetes mellitus","volume":"13","author":"Lim","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1167\/iovs.62.10.10","article-title":"Myeloid Cells in the Mouse Retina and Uveal Tract Respond Differently to Systemic Inflammatory Stimuli","volume":"62","author":"Dando","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s10792-021-02038-y","article-title":"Tasquinimod efficacy and S100A9 expression in glucose-treated HREC cells","volume":"42","author":"Jin","year":"2022","journal-title":"Int. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1158\/0008-5472.CAN-12-2730","article-title":"Tasquinimod is an allosteric modulator of HDAC4 survival signaling within the compromised cancer microenvironment","volume":"73","author":"Isaacs","year":"2013","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1158\/2326-6066.CIR-14-0036","article-title":"Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models","volume":"3","author":"Shen","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"681","DOI":"10.18240\/ijo.2026.04.06","article-title":"Ocular surface characteristics and dry eye symptoms in primary biliary cholangitis patients complicated with seasonal allergic conjunctivitis","volume":"19","author":"Ruan","year":"2026","journal-title":"Int. J. Ophthalmol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ajo.2005.03.057","article-title":"Standardization of Uveitis Nomenclature for Reporting Clinical Data: Results of the First International Workshop","volume":"140","author":"Jabs","year":"2005","journal-title":"Am. J. Ophthalmol."},{"key":"ref_53","unstructured":"(2021). Standardization of Uveitis Nomenclature (SUN) Working Group. Development of classification criteria for the uveitides. Am. J. Ophthalmol., 228, 96\u2013105."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/09273948.2018.1538461","article-title":"Circulating S100A8\/A9 Levels Reflect Intraocular Inflammation in Uveitis Patients","volume":"28","author":"Wang","year":"2020","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1080\/09273948.2018.1485956","article-title":"The Expression of Calprotectin and Factors in TLR4\/NF-\u03baB\/MyD88 Pathway in Patients with Idiopathic Acute Anterior Uveitis","volume":"27","author":"Song","year":"2019","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7653","DOI":"10.1167\/iovs.15-17066","article-title":"Elevated S100A8\/A9 and S100A12 Serum Levels Reflect Intraocular Inflammation in Juvenile Idiopathic Arthritis-Associated Uveitis: Results from a Pilot Study","volume":"56","author":"Walscheid","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"156675","DOI":"10.1016\/j.phymed.2025.156675","article-title":"Prunella vulgaris polyphenols alleviate liver injury-uveitis comorbidity by regulating acylcarnitine via the S100A9-PP2A-AMPK pathway","volume":"141","author":"Xie","year":"2025","journal-title":"Phytomedicine"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8449","DOI":"10.1167\/iovs.15-17524","article-title":"Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats","volume":"56","author":"Pepple","year":"2015","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bj\u00f6rk, P., Bj\u00f6rk, A., Vogl, T., Stenstr\u00f6m, M., Liberg, D., Olsson, A., Roth, J., Ivars, F., and Leanderson, T. (2009). Identification of human S100A9 as a novel target for treatment of autoimmune disease via binding to quinoline-3-carboxamides. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000097"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Frans\u00e9n Pettersson, N., Deronic, A., Nilsson, J., Hannibal, T.D., Hansen, L., Schmidt-Christensen, A., Ivars, F., and Holmberg, D. (2018). The immunomodulatory quinoline-3-carboxamide Paquinimod reverses established fibrosis in a novel mouse model for liver fibrosis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0203228"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1002\/art.33493","article-title":"Pharmacokinetics, tolerability, and preliminary efficacy of Paquinimod (ABR-215757), a new quinoline-3-carboxamide derivative: Studies in lupus-prone mice and a multicenter, randomized, double-blind, placebo-controlled, repeat-dose, dose-ranging study in patients with systemic lupus erythematosus","volume":"64","author":"Bengtsson","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"16958","DOI":"10.1021\/ja505986a","article-title":"Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing","volume":"136","author":"Nair","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1038\/s41423-025-01343-1","article-title":"Infiltrating macrophages replace Kupffer cells and play diverse roles in severe alcohol-associated hepatitis","volume":"22","author":"Wang","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e005319","DOI":"10.1136\/jitc-2022-005319","article-title":"Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma","volume":"11","author":"Fan","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3098","DOI":"10.1172\/JCI130546","article-title":"S100A8\/A9 regulates CD11b expression and neutrophil recruitment during chronic tuberculosis","volume":"130","author":"Scott","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"tkad030","DOI":"10.1093\/burnst\/tkad030","article-title":"S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion","volume":"11","author":"Zhang","year":"2023","journal-title":"Burns Trauma"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Demir, M.F., Lin, Y.H., Costa Cruz, P.H., Tajima, M., Honjo, T., and M\u00fcller, E. (2024). Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1479502"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1053\/j.gastro.2024.08.046","article-title":"Immune dysfunction and infection risk in advanced liver disease","volume":"168","author":"McGettigan","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2453515","DOI":"10.1080\/19420862.2025.2453515","article-title":"With great power, comes great responsibility: The importance of broadly measuring Fc-mediated effector function early in the antibody development process","volume":"17","author":"Crescioli","year":"2025","journal-title":"mAbs"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"World Medical Association (2025). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human participants. JAMA, 333, 71\u201374.","DOI":"10.1001\/jama.2024.21972"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"101338","DOI":"10.1016\/j.preteyeres.2025.101338","article-title":"A comprehensive scoping review of methodological approaches and clinical applications of tear fluid biomarkers","volume":"106","author":"Gijs","year":"2025","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102388","DOI":"10.1016\/j.clae.2025.102388","article-title":"Global practices of tear fluid collection, storage, and molecular analysis\u2014A questionnaire by the Tear Research Network","volume":"48","author":"Boychev","year":"2025","journal-title":"Contact Lens Anterior Eye"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e70377","DOI":"10.1111\/cts.70377","article-title":"Use of biomarkers in drug development for regulatory purposes","volume":"18","author":"Schuck","year":"2025","journal-title":"Clin. Transl. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/1535370217750088","article-title":"Biomarker definitions and their applications","volume":"243","author":"Califf","year":"2018","journal-title":"Exp. Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.2196\/jmir.7108","article-title":"The Effect of the General Data Protection Regulation on Medical Research","volume":"19","author":"Rumbold","year":"2017","journal-title":"J. Med. Internet Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/ijp.ijp_152_25","article-title":"International Council for Harmonisation E6 (R3): The Good Clinical Practice, Recent Developments, and Global Perspective","volume":"57","author":"Bharati","year":"2025","journal-title":"Indian J. Pharmacol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1306\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T04:26:37Z","timestamp":1786076797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/15\/1306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":76,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["biology15151306"],"URL":"https:\/\/doi.org\/10.3390\/biology15151306","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}