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We investigated the anti-inflammatory effect of GM1 ganglioside on endotoxin-induced uveitis (EIU) in rats and RAW 264.7 macrophages. Methods: EIU was induced in Lewis rats by administering a subcutaneous injection of lipopolysaccharide (LPS). GM1 was injected intraperitoneally for three consecutive days prior to the LPS injection. Twenty-four hours after the LPS injection, the integrity of the blood-aqueous barrier was evaluated by determining the protein concentration and number of infiltrating cells in the aqueous humor (AqH). Immunohistochemical and Western blot analyses of the iris-ciliary body (ICB) were performed to evaluate the effect of GM1 on the LPS-induced expression of cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1). The effect of GM1 on proinflammatory mediators and signaling cascades was examined in LPS-stimulated RAW 264.7 cells using Western blotting and immunofluorescence staining to further clarify the underlying anti-inflammatory mechanism. Results: GM1 significantly reduced the protein concentration and number of infiltrating cells in the AqH of rats with EIU. GM1 also decreased the LPS-induced expression of the ICAM-1 and COX-2 proteins in the ICB. In RAW 264.7 cells, GM1 inhibited the proinflammatory mediators induced by LPS, including inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor-\u03b1 (TNF-\u03b1), interleukin-1\u03b2 (IL-1\u03b2) and interleukin-6 (IL-6), and this inhibitory effect was potentially mediated by suppressing reactive oxygen species (ROS)-mediated activation of nuclear factor-\u03baB (NF-\u03baB) and mitogen-activated protein kinases (MAPKs). Conclusions: Based on this study, GM1 may be a potential anti-inflammatory agent for ocular inflammatory diseases.<\/jats:p>","DOI":"10.3390\/biom12050727","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T09:18:08Z","timestamp":1653124688000},"page":"727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Tzu-Heng","family":"Weng","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-Chih","family":"Ke","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Tri-Service General Hospital, School of Medicine, National Defense Medical Center, Taipei 11490, Taiwan"},{"name":"Graduate Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-6421","authenticated-orcid":false,"given":"Yuahn-Sieh","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1136\/bjo.2003.037226","article-title":"Degree, duration, and causes of visual loss in uveitis","volume":"88","author":"Durrani","year":"2004","journal-title":"Br. J. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2147\/OPTO.S72079","article-title":"Diagnosis and treatment of anterior uveitis: Optometric management","volume":"8","author":"Harthan","year":"2016","journal-title":"Clin. Optom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1136\/postgradmedj-2017-134891","article-title":"Uveitis: A sight-threatening disease which can impact all systems","volume":"93","author":"Krishna","year":"2017","journal-title":"Postgrad. Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejphar.2015.04.025","article-title":"The anti-inflammatory effects of palmitoylethanolamide (PEA) on endotoxin-induced uveitis in rats","volume":"761","author":"Impellizzeri","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-1-4939-9167-9_14","article-title":"Endotoxin-Induced Uveitis in Rodents","volume":"1960","author":"Yadav","year":"2019","journal-title":"Mouse Models of Innate Immunity. Methods in Molecular Biology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"326","DOI":"10.3389\/fphar.2018.00326","article-title":"Theissenolactone C Exhibited Ocular Protection of Endotoxin-Induced Uveitis by Attenuating Ocular Inflammatory Responses and Glial Activation","volume":"9","author":"Lin","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_7","first-page":"196","article-title":"An evaluation of ocular inflammation following the injection of bacterial endotoxin into the rat foot pad","volume":"24","author":"Bhattacherjee","year":"1983","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_8","first-page":"532","article-title":"Endotoxin-induced uveitis in the rat. The significance of intraocular interleukin-6","volume":"33","author":"Hoekzema","year":"1992","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","unstructured":"McMenamin, P.G., and Crewe, J. (1995). Endotoxin-induced uveitis. Kinetics and phenotype of the inflammatory cell infiltrate and the response of the resident tissue macrophages and dendritic cells in the iris and ciliary body. Investig. Ophthalmol. Vis. Sci., 36."},{"key":"ref_10","first-page":"619","article-title":"Expression of toll-like receptor 4 in uvea-resident tissue macrophages during endotoxin-induced uveitis","volume":"15","author":"Chen","year":"2009","journal-title":"Mol. Vis."},{"key":"ref_11","first-page":"359","article-title":"The anti-inflammatory effect of minocycline on endotoxin-induced uveitis and retinal inflammation in rats. 2019, 25, 359\u2013372","volume":"25","author":"Yuan","year":"2019","journal-title":"Mol. Vis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/0014-4835(84)90065-4","article-title":"Endotoxin-induced uveitis in the rat: Observations on altered vascular permeability, clinical findings, and histology","volume":"39","author":"Cousins","year":"1984","journal-title":"Exp. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Park, J., Kim, J.T., Lee, S.J., and Kim, J.C. (2022). The anti-inflammatory effects of angiogenin in an endotoxin induced uveitis in rats. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21020413"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1517\/14656561003713534","article-title":"Pharmacotherapy of uveitis","volume":"11","author":"Lee","year":"2010","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3109\/08820538.2014.959203","article-title":"Side-Effects of Anti-Inflammatory Therapy in Uveitis","volume":"29","author":"Uchiyama","year":"2014","journal-title":"Semin. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6548","DOI":"10.2174\/0929867327666200103093340","article-title":"The Structural Role of Gangliosides: Insights from X-ray Scattering on Model Membranes","volume":"27","author":"Andreev","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/bs.pmbts.2017.12.007","article-title":"Gangliosides in Membrane Organization","volume":"156","author":"Sonnino","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1900638","DOI":"10.1002\/cbdv.201900638","article-title":"Chemical Constituents and Bioactivities of Starfishes: An Update","volume":"17","author":"Xia","year":"2020","journal-title":"Chem. Biodivers."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/42.2.8288861","article-title":"Ultrastructural localization of gangliosides; GM1 is concentrated in caveolae","volume":"42","author":"Parton","year":"1994","journal-title":"J. Histochem. Cytochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S440","DOI":"10.1194\/jlr.R800028-JLR200","article-title":"The role of glycosphingolipid metabolism in the developing brain","volume":"50","author":"Yu","year":"2009","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8412","DOI":"10.1073\/pnas.072211699","article-title":"Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration","volume":"99","author":"Vyas","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ryckman, A.E., Brockhausen, I., and Walia, J.S. (2020). Metabolism of Glycosphingolipids and Their Role in the Pathophysiology of Lysosomal Storage Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186881"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"572965","DOI":"10.3389\/fnins.2020.572965","article-title":"Gangliosides in the Brain: Physiology, Pathophysiology and Therapeutic Applications","volume":"14","author":"Sipione","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/bs.pmbts.2018.01.009","article-title":"Gangliosides in Inflammation and Neurodegeneration","volume":"156","author":"Furukawa","year":"2018","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/j.1471-4159.2010.07067.x","article-title":"Gangliosides are essential in the protection of inflammation and neurodegeneration via maintenance of lipid rafts: Elucidation by a series of ganglioside-deficient mutant mice","volume":"116","author":"Ohmi","year":"2011","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chiricozzi, E., Lunghi, G., Di Biase, E., Fazzari, M., Sonnino, S., and Mauri, L. (2020). GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030868"},{"key":"ref_27","first-page":"239","article-title":"GM1 and GD1a gangliosides modulate toxic and inflammatory effects of E. coli lipopolysaccharide by preventing TLR4 translocation into lipid rafts","volume":"1851","author":"Nikolaeva","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cyto.2008.01.009","article-title":"Ganglioside GM1 effects on the expression of nerve growth factor (NGF), Trk-A receptor, proinflammatory cytokines and on autoimmune diabetes onset in non-obese diabetic (NOD) mice","volume":"42","author":"Vieira","year":"2008","journal-title":"Cytokine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.intimp.2011.02.022","article-title":"Immunomodulatory and anti-fibrotic effects of ganglioside therapy on the cardiac chronic form of experimental Trypanosoma cruzi infection","volume":"11","author":"Cutrullis","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.molimm.2018.02.001","article-title":"Ganglioside GM1 protects against high altitude cerebral edema in rats by suppressing the oxidative stress and inflammatory response via the PI3K\/AKT-Nrf2 pathway","volume":"95","author":"Gong","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1046\/j.1440-1711.1998.00783.x","article-title":"Basic pathogenic mechanisms operating in experimental models of acute anterior uveitis","volume":"76","author":"Smith","year":"1998","journal-title":"Immunol. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Qin, Y.J., Chu, K.O., Yip, Y.W.Y., Li, W.Y., Yang, Y.P., Chan, K.P., Ren, J.L., Chan, S.O., and Pang, C.P. (2014). Green Tea Extract Treatment Alleviates Ocular Inflammation in a Rat Model of Endotoxin-Induced Uveitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0103995"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1159\/000267163","article-title":"Retino-Choroidal Changes in Endotoxin-Induced Uveitis in the Rat","volume":"24","author":"Thillaye","year":"1992","journal-title":"Ophthalmic Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1292\/jvms.10-0239","article-title":"Anti-inflammatory potency of oral disulfiram compared with dexamethasone on endotoxin-induced uveitis in rats","volume":"73","author":"Kanai","year":"2011","journal-title":"J. Vet. Med. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1080\/15476286.2019.1632633","article-title":"Aminoglycoside drugs induce efficient read-through of CDKL5 nonsense mutations, slightly restoring its kinase activity","volume":"16","author":"Fazzari","year":"2019","journal-title":"RNA Biol."},{"key":"ref_36","first-page":"174","article-title":"Role of ICAM-1 and LFA-1 in endotoxin-induced uveitis in mice","volume":"40","author":"Kanagawa","year":"1996","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jss.2013.11.003","article-title":"Isotetrandrine protects against lipopolysaccharide-induced acute lung injury by suppression of mitogen-activated protein kinase and nuclear factor-kappa B","volume":"187","author":"Liang","year":"2014","journal-title":"J. Surg. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.cellsig.2012.01.018","article-title":"The macrophage response towards LPS and its control through the p38MAPK\u2013STAT3 axis","volume":"24","author":"Bode","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fgene.2019.00031","article-title":"RNA-Binding Proteins in the Control of LPS-Induced Macrophage Response","volume":"10","author":"Ostareck","year":"2019","journal-title":"Front. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Herb, M., and Schramm, M. (2021). Functions of ROS in Macrophages and Antimicrobial Immunity. Antioxidants, 10.","DOI":"10.3390\/antiox10020313"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/emm.2005.42","article-title":"beta-Carotene inhibits inflammatory gene expression in lipopolysaccharide-stimulated macrophages by suppressing redox-based NF-kappaB activation","volume":"37","author":"Bai","year":"2005","journal-title":"Exp. Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1152\/physrev.00044.2005","article-title":"The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology","volume":"87","author":"Bedard","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Cheng, C., Zou, Y., and Peng, J. (2018). Oregano Essential Oil Attenuates RAW264.7 Cells from Lipopolysaccharide-Induced Inflammatory Response through Regulating NADPH Oxidase Activation-Driven Oxidative Stress. Molecules, 23.","DOI":"10.3390\/molecules23081857"},{"key":"ref_44","first-page":"349","article-title":"Beyond oxidative stress: An immunologist\u2019s guide to reactive oxygen species, Nature reviews","volume":"13","author":"Nathan","year":"2013","journal-title":"Immunology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jep.2007.08.011","article-title":"Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF-kappaB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage","volume":"114","author":"Kim","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1089\/10445490260099746","article-title":"Ocular Immune Privilege and the Impact of Intraocular Inflammation","volume":"21","author":"Streilein","year":"2002","journal-title":"DNA Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Chen, C.-L., Chen, J.-T., Liang, C.-M., Tai, M.-C., Lu, D.-W., and Chen, Y.-H. (2017). Silibinin treatment prevents endotoxin-induced uveitis in rats in vivo and in vitro. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174971"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5441","DOI":"10.1167\/iovs.08-1784","article-title":"Inhibitory Effects of Glucosamine on Endotoxin-Induced Uveitis in Lewis Rats","volume":"49","author":"Chang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"671417","DOI":"10.1155\/2015\/671417","article-title":"Macrophages and Uveitis in Experimental Animal Models","volume":"2015","author":"Palacios","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"748218","DOI":"10.1155\/2010\/748218","article-title":"Expression of TLR4-MyD88 and NF-kappaB in the iris during endotoxin-induced uveitis","volume":"2010","author":"Li","year":"2010","journal-title":"Mediat. Inflamm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5584","DOI":"10.1167\/iovs.17-22679","article-title":"The Anti-Inflammatory Effect of Ripasudil (K-115), a Rho Kinase (ROCK) Inhibitor, on Endotoxin-Induced Uveitis in Rats","volume":"58","author":"Uchida","year":"2017","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0898-6568(00)00149-2","article-title":"LPS induction of gene expression in human monocytes","volume":"13","author":"Guha","year":"2001","journal-title":"Cell. Signal."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1177\/0022034510381264","article-title":"TLR-signaling networks: An integration of adaptor molecules, kinases, and cross-talk","volume":"90","author":"Brown","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.0105-2896.2004.00180.x","article-title":"Manipulation of mitogen-activated protein kinase\/nuclear factor-kappaB-signaling cascades during intracellular Toxoplasma gondii infection","volume":"201","author":"Denkers","year":"2004","journal-title":"Immunol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-activated protein kinases in innate immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0171-2985(97)80025-3","article-title":"Regulation of NF-kappa B activation by MAP kinase cascades","volume":"198","author":"Ferrari","year":"1997","journal-title":"Immunobiology"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Canton, M., S\u00e1nchez-Rodr\u00edguez, R., Spera, I., Venegas, F.C., Favia, M., Viola, A., and Castegna, A. (2021). Reactive Oxygen Species in Macrophages: Sources and Targets. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.734229"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1002\/jcb.26287","article-title":"Ganglioside GM3 suppresses lipopolysaccharide-induced inflammatory responses in rAW 264.7 macrophage cells through NF-kappaB, AP-1, and MAPKs signaling","volume":"119","author":"Park","year":"2018","journal-title":"J. Cell. Biochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.intimp.2015.05.044","article-title":"Ganglioside GD1a suppresses LPS-induced pro-inflammatory cytokines in RAW264.7 macrophages by reducing MAPKs and NF-kappaB signaling pathways through TLR4","volume":"28","author":"Wang","year":"2015","journal-title":"Int. Immunopharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.iac.2016.06.001","article-title":"An Overview of Nonsteroidal Antiinflammatory Drug Reactions","volume":"36","author":"Walters","year":"2016","journal-title":"Immunol. Allergy Clin. N. Am."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s40123-013-0020-5","article-title":"Intraocular Pressure Effects of Common Topical Steroids for Post-Cataract Inflammation: Are They All the Same?","volume":"2","author":"Pleyer","year":"2013","journal-title":"Ophthalmol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"460","DOI":"10.4103\/0019-5154.139874","article-title":"Systemic side-effects of topical corticosteroids","volume":"59","author":"Dhar","year":"2014","journal-title":"Indian J. Dermatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"524223","DOI":"10.3389\/fonc.2020.524223","article-title":"Ganglioside Monosialic Acid Alleviates Peripheral Neuropathy Induced by Utidelone Plus Capecitabine in Metastatic Breast Cancer From a Phase III Clinical Trial","volume":"10","author":"Xu","year":"2020","journal-title":"Front. 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