{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T01:57:09Z","timestamp":1784599029042,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sunstar Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NeuroSci"],"abstract":"<jats:p>Insufficient sleep and circadian misalignment increase inflammatory agents. This triggers neuroinflammation and can result in health issues including depression, dementia, lifestyle-related diseases, and industrial accidents. Lactoferrin (LF) confers neuroprotective effects, which are derived from its anti-inflammatory, antioxidant, and iron metabolic properties; however, its roles in acute neuroinflammation and circadian rhythm disruption are yet to be elucidated. Therefore, we aimed to test the effects of LF on rat neuroinflammation and sleep and jetlag in humans. Rats received 7 days of an oral liposomal bovine LF (L-bLF) or vehicle followed by polyriboinosinic:polyribocytidylic acid (poly I:C) peritoneal injections (n = 5\u20136). Compared with the rats given poly I:C only, the rats given L-bLF and poly I:C had lower Il1b, Tnf, Casp1, Nfe212, Gclm, and Sod2 expression in the hippocampus. This open-label pilot study was carried out on tour conductors performing regular international tour responsibilities, and the data were compared between the initial tour without L-bLF intake and the subsequent tour with L-bLF intake. In the tour with L-bLF intake, L-bLF administration started from one week before the trip and was continued during the trip. In both periods, the tour conductors experienced limited sleep; however, both subjective and objective sleep quality was significantly better with the oral L-bLF intake than without. Overall, we found that prophylactic L-bLF supplementation reduced neuroinflammation in rat hippocampi and improved sleep quality and jetlag in tour conductors.<\/jats:p>","DOI":"10.3390\/neurosci6010019","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T03:22:44Z","timestamp":1740972164000},"page":"19","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liposomal Lactoferrin Reduces Brain Neuroinflammation in Rats and Alleviates Jetlag and Improves Sleep Quality After Long-Haul Travel"],"prefix":"10.3390","volume":"6","author":[{"given":"Shoko","family":"Uesaki","sequence":"first","affiliation":[{"name":"R&D Department, Sunstar Inc., 3-1 Asahimachi, Takatsuki 569-1195, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Yamato","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"},{"name":"Graduate School of Science, Technology and Innovation, Kobe University, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9329-8608","authenticated-orcid":false,"given":"Atsushi","family":"Ishikado","sequence":"additional","affiliation":[{"name":"R&D Department, Sunstar Inc., 3-1 Asahimachi, Takatsuki 569-1195, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Suekawa","sequence":"additional","affiliation":[{"name":"R&D Department, Sunstar Inc., 3-1 Asahimachi, Takatsuki 569-1195, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1586-3111","authenticated-orcid":false,"given":"Yasuhisa","family":"Tamura","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"},{"name":"Graduate School of Science, Technology and Innovation, Kobe University, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"},{"name":"Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikori-Kita, Tondabayashi 584-8540, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6658-4163","authenticated-orcid":false,"given":"Yosky","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"},{"name":"Graduate School of Science, Technology and Innovation, Kobe University, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"153951","DOI":"10.1016\/j.metabol.2019.153951","article-title":"Neuroinflammation disorders exacerbated by environmental stressors","volume":"100","author":"Miller","year":"2019","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbi.2015.01.004","article-title":"Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance","volume":"47","author":"Wright","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_3","unstructured":"Kryger, M., Roth, T., and Dement, W.C. (2017). Sleep and host defence. Principles and Practice of Sleep Medicine, Elsevier. [6th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8071","DOI":"10.1007\/s12035-016-0297-1","article-title":"Inflammatory response in the CNS: Friend or foe?","volume":"54","author":"Sochocka","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.beem.2010.08.014","article-title":"Sleep loss and inflammation","volume":"24","author":"Mullington","year":"2010","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/01616412.2023.2296754","article-title":"Minocycline mitigates tau pathology via modulating the TLR-4\/NF-\u043a\u03b2 signalling pathway in the hippocampus of neuroinflammation rat model","volume":"46","author":"Abdullah","year":"2024","journal-title":"Neurol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6654","DOI":"10.1021\/acsomega.0c04810","article-title":"Curcumin reduces cognitive deficits by inhibiting neuroinflammation through the endoplasmic reticulum stress pathway in apolipoprotein E4 transgenic mice","volume":"6","author":"Kou","year":"2021","journal-title":"ACS Omega"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7834381","DOI":"10.1155\/2018\/7834381","article-title":"Royal jelly attenuates LPS-induced inflammation in BV-2 microglial cells through modulating NF-\u03baB and p38\/JNK signaling pathways","volume":"2018","author":"You","year":"2018","journal-title":"Mediators Inflamm."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Khan, A., Ikram, M., Muhammad, T., Park, J., and Kim, M.O. (2019). Caffeine modulates cadmium-induced oxidative stress, neuroinflammation, and cognitive impairments by regulating Nrf-2\/HO-1 in vivo and in vitro. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050680"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jpeds.2016.02.071","article-title":"Overview of lactoferrin as a natural immune modulator","volume":"173","author":"Legrand","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, Y.Q., and Guo, C. (2021). A review on lactoferrin and central nervous system diseases. Cells, 10.","DOI":"10.3390\/cells10071810"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bolat, E., Eker, F., Kaplan, M., Duman, H., Arslan, A., Sarita\u015f, S., \u015eahuto\u011flu, A.S., and Karav, S. (2022). Lactoferrin for COVID-19 prevention, treatment, and recovery. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.992733"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Cutone, A., Rosa, L., Ianiro, G., Lepanto, M.S., Bonaccorsi di Patti, M.C., Valenti, P., and Musci, G. (2020). Lactoferrin\u2019s anti-cancer properties: Safety, selectivity, and wide range of action. Biomolecules, 10.","DOI":"10.3390\/biom10030456"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Elzoghby, A.O., Abdelmoneem, M.A., Hassanin, I.A., Abd Elwakil, M.M., Elnaggar, M.A., Mokhtar, S., Fang, J.Y., and Elkhodairy, K.A. (2020). Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand. Biomaterials, 263.","DOI":"10.1016\/j.biomaterials.2020.120355"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1017\/S0007114500002191","article-title":"Occurrence, structure, biochemical properties and technological characteristics of lactoferrin","volume":"84","author":"Steijns","year":"2000","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Presti, S., Manti, S., Parisi, G.F., Papale, M., Barbagallo, I.A., Li Volti, G., and Leonardi, S. (2021). Lactoferrin: Cytokine modulation and application in clinical practice. J. Clin. Med., 10.","DOI":"10.3390\/jcm10235482"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/aps.2013.200","article-title":"Immunomodulatory effects of lactoferrin","volume":"35","year":"2014","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107571","DOI":"10.1016\/j.intimp.2021.107571","article-title":"The potential for lactoferrin to reduce SARS-CoV-2 induced cytokine storm","volume":"95","author":"Zimecki","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","first-page":"433","article-title":"Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo","volume":"74","author":"Machnicki","year":"1993","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0008-8749(03)00006-6","article-title":"Lactoferrin down-regulates the LPS-induced cytokine production in monocytic cells via NF-kappa B","volume":"220","author":"Ohlsson","year":"2002","journal-title":"Cell Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23527","DOI":"10.1074\/jbc.M111.324673","article-title":"Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharide-mediated osteoclastogenesis","volume":"287","author":"Inubushi","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0169-328X(01)00216-9","article-title":"Lactoferrin is synthesized by activated microglia in the human substantia nigra and its synthesis by the human microglial CHME cell line is upregulated by tumor necrosis factor alpha or 1-methyl-4-phenylpyridinium treatment","volume":"96","author":"Fillebeen","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5516","DOI":"10.1038\/s41380-021-01248-1","article-title":"The acute phase protein lactoferrin is a key feature of Alzheimer\u2019s disease and predictor of A\u03b2 burden through induction of APP amyloidogenic processing","volume":"26","author":"Tsatsanis","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1038\/npp.2017.8","article-title":"Intranasal lactoferrin enhances \u03b1-secretase-dependent amyloid precursor protein processing via the ERK1\/2-CREB and HIF-1\u03b1 pathways in an Alzheimer\u2019s disease mouse model","volume":"42","author":"Guo","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_25","first-page":"1574","article-title":"Lactotransferrin immunocytochemistry in Alzheimer and normal human brain","volume":"142","author":"Kawamata","year":"1993","journal-title":"Am. J. Pathol."},{"key":"ref_26","first-page":"1342","article-title":"Neuroprotective effects of lactoferrin in Alzheimer\u2019s and Parkinson\u2019s diseases: A narrative review","volume":"14","author":"Yong","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.biopha.2018.12.118","article-title":"A pilot study on the effect of lactoferrin on Alzheimer\u2019s disease pathological sequelae: Impact of the p-Akt\/PTEN pathway","volume":"111","author":"Mohamed","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"103736","DOI":"10.1016\/j.jff.2019.103736","article-title":"Lactoferrin improves cognitive function and attenuates brain senescence in aged mice","volume":"65","author":"Zheng","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/biof.552210113","article-title":"Liposomal lactoferrin induced significant increase of the interferon-alpha (IFN-alpha) producibility in healthy volunteers","volume":"21","author":"Ishikado","year":"2004","journal-title":"Biofactors"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1248\/bpb.28.1717","article-title":"Liposomalization of lactoferrin enhanced it\u2019s anti-inflammatory effects via oral administration","volume":"28","author":"Ishikado","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/labinvest.2010.80","article-title":"Inhibitory effects of orally administrated liposomal bovine lactoferrin on the LPS-induced osteoclastogenesis","volume":"90","author":"Yamano","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1248\/bpb.33.1758","article-title":"Human trial of liposomal lactoferrin supplementation for periodontal disease","volume":"33","author":"Ishikado","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_33","first-page":"55","article-title":"Effects of lactoferrin supplementation on sleep quality, mood states, and enteric environment in poor sleepers-randomized, placebo-controlled, double-blind study","volume":"46","author":"Uesaki","year":"2018","journal-title":"Jpn. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Yamato, M., Tamura, Y., Eguchi, A., Kume, S., Miyashige, Y., Nakano, M., Watanabe, Y., and Kataoka, Y. (2014). Brain interleukin-1\u03b2 and the intrinsic receptor antagonist control peripheral toll-like receptor 3-mediated suppression of spontaneous activity in rats. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090950"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3147\/jsfp.47.137","article-title":"RSIV is probably insensitive to the transient innate immune response induced by administration of poly(I:C), a synthetic double-stranded RNA","volume":"47","author":"Kim","year":"2012","journal-title":"Fish. Pathology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0306-4522(03)00365-8","article-title":"Prolonged effects of polyriboinosinic: Polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: A model for immunologically induced fatigue","volume":"120","author":"Katafuchi","year":"2003","journal-title":"Neuroscience"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ketelauri, P., Scharov, K., von Gall, C., and Johann, S. (2023). Acute circadian disruption due to constant light promotes caspase 1 activation in the mouse hippocampus. Cells, 12.","DOI":"10.3390\/cells12141836"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.jneuroim.2010.05.022","article-title":"Aging sensitizes rapidly isolated hippocampal microglia to LPS ex vivo","volume":"226","author":"Frank","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbi.2008.07.002","article-title":"Time course of hippocampal IL-1 beta and memory consolidation impairments in aging rats following peripheral infection","volume":"23","author":"Barrientos","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1378\/chest.14-0970","article-title":"International classification of sleep disorders-third edition: Highlights and modifications","volume":"146","author":"Sateia","year":"2014","journal-title":"Chest"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"148916","DOI":"10.1016\/j.brainres.2024.148916","article-title":"Effects of sleep deprivation on anxiety-depressive-like behavior and neuroinflammation","volume":"1836","author":"Cao","year":"2024","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jerigova, V., Zeman, M., and Okuliarova, M. (2022). Circadian disruption and consequences on innate immunity and inflammatory response. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232213722"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/978-981-19-7376-5_12","article-title":"Sleep immune cross talk and insomnia","volume":"1411","author":"Akkaoui","year":"2023","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.jsmc.2023.02.003","article-title":"Sleep and inflammation: Bidirectional relationship","volume":"18","author":"Veler","year":"2023","journal-title":"Sleep. Med. Clin."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0165-1781(00)00232-8","article-title":"Psychometric assessment of subjective sleep quality using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) in psychiatric disordered and control subjects","volume":"97","author":"Doi","year":"2000","journal-title":"Psychiatry Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/S0140-6736(07)60529-7","article-title":"Jet lag: Trends and coping strategies","volume":"369","author":"Waterhouse","year":"2007","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13","DOI":"10.11560\/jahp.13.1_13","article-title":"Characteristics of personality affecting on sleep feeling: Study for neuroticism and extroversion-introversion","volume":"13","author":"Yamamoto","year":"2000","journal-title":"Jpn. J. Health Psychol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Huang, W.C., Liou, C.J., Shen, S.C., Hu, S., Chao, J.C., Hsiao, C.Y., and Wu, S.J. (2022). Urolithin A inactivation of TLR3\/TRIF signaling to block the NF-\u03baB\/STAT1 axis reduces inflammation and enhances antioxidant defense in poly(I:C)-induced RAW264.7 cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094697"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1038\/sj.cdd.4401850","article-title":"TLR signaling","volume":"13","author":"Kawai","year":"2006","journal-title":"Cell Death Differ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"109575","DOI":"10.1016\/j.neuropharm.2023.109575","article-title":"Lactoferrin averts neurological and behavioral impairments of thioacetamide-induced hepatic encephalopathy in rats via modulating HGMB1\/TLR-4\/MyD88\/Nrf2 pathway","volume":"236","author":"Essam","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s12974-018-1083-y","article-title":"Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo","volume":"15","author":"Liu","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2390","DOI":"10.4103\/1673-5374.313031","article-title":"Caspase-1: An important player and possible target for repair of the blood-brain barrier underlying neurodegeneration","volume":"16","author":"Rand","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100533","DOI":"10.1016\/j.crfs.2023.100533","article-title":"Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis","volume":"7","author":"He","year":"2023","journal-title":"Curr. Res. Food Sci."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"He, F., Ru, X., and Wen, T. (2020). NRF2, a transcription factor for stress response and beyond. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134777"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"680","DOI":"10.4049\/jimmunol.181.1.680","article-title":"The transcription factor Nrf2 is a therapeutic target against brain inflammation","volume":"181","author":"Innamorato","year":"2008","journal-title":"J. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/1476-4598-13-217","article-title":"Transfection of poly(I:C) can induce reactive oxygen species-triggered apoptosis and interferon-\u03b2-mediated growth arrest in human renal cell carcinoma cells via innate adjuvant receptors and the 2-5A system","volume":"13","author":"Harashima","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1016\/j.biopha.2018.10.019","article-title":"Crosstalk of toll-like receptors signaling and Nrf2 pathway for regulation of inflammation","volume":"108","author":"Mohan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Saha, S., Buttari, B., Panieri, E., Profumo, E., and Saso, L. (2020). An overview of Nrf2 signaling pathway and its role in inflammation. Molecules, 25.","DOI":"10.3390\/molecules25225474"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11373-006-9121-7","article-title":"Characterization of lactoferrin receptor in brain endothelial capillary cells and mouse brain","volume":"14","author":"Huang","year":"2007","journal-title":"J. Biomed. Sci."},{"key":"ref_60","first-page":"115","article-title":"Suppressive effect of lactoferrin with 70 irons via oral administration on dysmenorrheal","volume":"59","author":"Yoshise","year":"2010","journal-title":"Milk. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1292\/jvms.70.313","article-title":"Trans-endothelial and trans-epithelial transfer of lactoferrin into the brain through BBB and BCSFB in adult rats","volume":"70","author":"Kamemori","year":"2008","journal-title":"J. Vet. Med. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Zielinski, M.R., and Gibbons, A.J. (2022). Neuroinflammation, Sleep, and Circadian Rhythms. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.853096"},{"key":"ref_63","unstructured":"Kryger, M., Roth, T., and Dement, W.C. (2017). Shift work, shift-work disorder, and jet lag. Principles and Practice of Sleep Medicine, Elsevier. [6th ed.]."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.2174\/1874467214999210111211947","article-title":"Bovine lactoferrin as a modulator of neuroendocrine components of stress","volume":"14","year":"2021","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_65","first-page":"43","article-title":"The potentiating action of bovine lactoferrin on the light entrainment of the circadian clock in mice","volume":"2017","author":"Moriya","year":"2017","journal-title":"Lactoferrin"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1957407","DOI":"10.1080\/19490976.2021.1957407","article-title":"Sleep, circadian rhythm and gut microbiota: Alterations in Alzheimer\u2019s disease and their potential links in the pathogenesis","volume":"13","author":"Li","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5796","DOI":"10.4049\/jimmunol.1001026","article-title":"Dysregulation of inflammatory responses by chronic circadian disruption","volume":"185","author":"Wu","year":"2010","journal-title":"J. Immunol."}],"container-title":["NeuroSci"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2673-4087\/6\/1\/19\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:45:25Z","timestamp":1760028325000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2673-4087\/6\/1\/19"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,1]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["neurosci6010019"],"URL":"https:\/\/doi.org\/10.3390\/neurosci6010019","relation":{},"ISSN":["2673-4087"],"issn-type":[{"value":"2673-4087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,1]]}}}