{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:03:00Z","timestamp":1784955780916,"version":"3.55.0"},"reference-count":61,"publisher":"Japanese Society for Dental Materials and Devices","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dent. Mater. J.","Dental Materials Journal"],"published-print":{"date-parts":[[2026,7,25]]},"DOI":"10.4012\/dmj.2025-314","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T22:09:50Z","timestamp":1781906990000},"page":"437-449","source":"Crossref","is-referenced-by-count":0,"title":["Biochemical and transcriptomic characterization of low-molecular-weight fucoidan with potential applications in oral biomaterials"],"prefix":"10.4012","volume":"45","author":[{"given":"Shunya","family":"OKA","sequence":"first","affiliation":[{"name":"Department of Biology, The Nippon Dental University School of Life Dentistry at Niigata"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"KAMEDA","sequence":"additional","affiliation":[{"name":"Department of Orthodontics, The Nippon Dental University School of Life Dentistry at Niigata"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"TORII","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo W.","family":"TSUTSUI","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichi","family":"TSUBURA","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University School of Life Dentistry at Niigata"},{"name":"Tsubura Dental Clinic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akane","family":"IMAI","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life Dentistry at Niigata, The Nippon Dental University School of Life Dentistry at Niigata"},{"name":"Department of Dental Hygiene, The Nippon Dental University College at Niigata"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2427","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1) Kylin H. Zur Biochemie der Meeresalgen. Hoppe-Seyler\u00b4s Zeitschrift fu\u0308r physiologische Chemie 1913. p. 171.","DOI":"10.1515\/bchm2.1913.83.3.171"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Sakai T, Ishizuka K, Shimanaka K, Ikai K, Kato I. Structures of oligosaccharides derived from <i>Cladosiphon okamuranus<\/i> fucoidan by digestion with marine bacterial enzymes. Mar Biotechnol 2003; 5: 536-544.","DOI":"10.1007\/s10126-002-0107-9"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Berteau O, Mulloy B. Sulfated fucans, fresh perspectives: Structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide. Glycobiology 2003; 13: 29-40.","DOI":"10.1093\/glycob\/cwg058"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Usui T, Asari K, Mizuno T. Isolation of highly purified fucoidan from <i>Eisenia bicyclis<\/i> and its anticoagulant and antitumor activities. Agric Biol Chem 1980; 44: 1965-1966.","DOI":"10.1271\/bbb1961.44.1965"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Senthilkumar K, Manivasagan P, Venkatesan J, Kim S-K. Brown seaweed fucoidan: Biological activity and apoptosis, growth signaling mechanism in cancer. Int J Biol Macromol 2013; 60: 366-374.","DOI":"10.1016\/j.ijbiomac.2013.06.030"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Dinesh S, Menon T, Hanna LE, Suresh V, Sathuvan M, Manikannan M. In vitro anti-HIV-1 activity of fucoidan from <i>Sargassum swartzii<\/i>. Int J Biol Macromol 2016; 82: 83-88.","DOI":"10.1016\/j.ijbiomac.2015.09.078"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Teixeira MM, Hellewell PG. The effect of the selectin binding polysaccharide fucoidin on eosinophil recruitment in vivo. Br J Pharmacol 1997; 120: 1059-1066.","DOI":"10.1038\/sj.bjp.0701024"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) de Jesus Raposo MF, De Morais AMB, De Morais RMSC. Marine polysaccharides from algae with potential biomedical applications. Mar Drugs 2015; 13: 2967-3028.","DOI":"10.3390\/md13052967"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Tsubura S, Tsubura T, Waki Y. Recurrent aphthous stomatitis treated with fucoidan. J Cranio Max Dis 2012; 1: 105-108.","DOI":"10.4103\/2278-9588.105699"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Tsubura S, Waki Y, Tsubura T. A case of symptomatic inflammatory tongue treated with fucoidan. Am J Med Case Rep 2015; 3: 250-254.","DOI":"10.12691\/ajmcr-3-8-8"},{"key":"11","unstructured":"11) Tsubura S, Suzuki A. Case report using 4% fucoidan cream for recurrent oral herpes labialis: Patient symptoms markedly improved in terms of time to healing and time to loss of discomfort. Dent Open J 2017; 4: 19-23."},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Tsubura S, Kanazawa M, Oka S, Hirama R, Tsubura T. Using PF-MOUTH GELTM for sore or painful tongue improved symptoms and stabilized dryness and trapping of food: A case report. Dent Open J 2021; 7: 7-11.","DOI":"10.17140\/DOJ-7-143"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Oka S, Okabe M, Tsubura S, Mikami M, Imai A. Properties of fucoidans beneficial to oral healthcare. Odontology 2020; 108: 34-42.","DOI":"10.1007\/s10266-019-00437-3"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Makgobole MU, Onwubu S, Khathi A, Mpofana N, Mkhwanazi B. Cosmeceuticals from marine: The prospect of marine products in skin rejuvenation and care. Egypt J Basic Appl Sci 2024; 11: 297-317.","DOI":"10.1080\/2314808X.2024.2336307"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Kuznetsova N, Leikin S. Does the triple helical domain of type I collagen encode molecular recognition and fiber assembly while telopeptides serve as catalytic domains?: Effect of proteolytic cleavage on fibrillogenesis and on collagen-collagen interaction in fibers. J Biol Chem 1999; 274: 36083-36088.","DOI":"10.1074\/jbc.274.51.36083"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Letra A, Silva RM, Rylands RJ, Silveira EM, de Souza AP, Wendell SK, <i>et al.<\/i> MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression. J Clin Periodontol 2012; 39: 707-716.","DOI":"10.1111\/j.1600-051X.2012.01902.x"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Preshaw PM. Host modulation therapy with anti-inflammatory agents. Periodontol 2000 2018; 76: 131-149.","DOI":"10.1111\/prd.12148"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Choi DH, Moon IS, Choi BK, Paik JW, Kim YS, Choi SH, <i>et al.<\/i> Effects of sub-antimicrobial dose doxycycline therapy on crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic periodontitis. J Periodontal Res 2004; 39: 20-26.","DOI":"10.1111\/j.1600-0765.2004.00696.x"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Kumar MS, Vamsi G, Sripriya R, Sehgal PK. Expression of matrix metalloproteinases (MMP-8 and-9) in chronic periodontitis patients with and without diabetes mellitus. J Periodontol 2006; 77: 1803-1808.","DOI":"10.1902\/jop.2006.050293"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Marcaccini AM, Meschiari CA, Zuardi LR, De Sousa TS, Taba Jr M, Teofilo JM, <i>et al.<\/i> Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. J Clin Periodontol 2010; 37: 180-190.","DOI":"10.1111\/j.1600-051X.2009.01512.x"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Tu C, Ortega-Cava CF, Chen G, Fernandes ND, Cavallo-Medved D, Sloane BF, <i>et al.<\/i> Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts. Cancer Res 2008; 68: 9147-9156.","DOI":"10.1158\/0008-5472.CAN-07-5127"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Li X, Wu J-F. Recent developments in patent anti-cancer agents targeting the matrix metalloproteinases (MMPs). Recent Pat Anticancer Drug Discov 2010; 5: 109-141.","DOI":"10.2174\/157489210790936234"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Lee KW, Lee HJ. Biphasic effects of dietary antioxidants on oxidative stress-mediated carcinogenesis. Mech Ageing Dev 2006; 127: 424-431.","DOI":"10.1016\/j.mad.2006.01.021"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Lee S-H, Kang M-C, Moon S-H, Jeon B-T, Jeon Y-J. Potential use of ultrasound in antioxidant extraction from Ecklonia cava. Algae 2013; 28: 371-378.","DOI":"10.4490\/algae.2013.28.4.371"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Mak W, Hamid N, Liu T, Lu J, White W. Fucoidan from New Zealand Undaria pinnatifida: Monthly variations and determination of antioxidant activities. Carbohydr Polym 2013; 95: 606-614.","DOI":"10.1016\/j.carbpol.2013.02.047"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Wang J, Zhang Q, Zhang Z, Song H, Li P. Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 2010; 46: 6-12.","DOI":"10.1016\/j.ijbiomac.2009.10.015"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Yuan Y, Macquarrie D. Microwave assisted extraction of sulfated polysaccharides (fucoidan) from Ascophyllum nodosum and its antioxidant activity. Carbohydr Polym 2015; 129: 101-107.","DOI":"10.1016\/j.carbpol.2015.04.057"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Wang Y, Xing M, Cao Q, Ji A, Liang H, Song S. Biological activities of fucoidan and the factors mediating its therapeutic effects: A review of recent studies. Mar Drugs 2019; 17: 183.","DOI":"10.3390\/md17030183"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Kirsten N, Ohmes J, Mikkelsen MD, Nguyen TT, Bl\u00fcmel M, Wang F, <i>et al.<\/i> Impact of enzymatically extracted high molecular weight fucoidan on lipopolysaccharide-induced endothelial activation and leukocyte adhesion. Mar Drugs 2023; 21: 339.","DOI":"10.3390\/md21060339"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Kumaran T, Yahya S, Sudhandiran G, Shanmugam P, Kathiravan K. Isolation, structural characterization, and anti-lung cancer evaluation of fucoidan isolated from the brown seaweed Turbinaria decurrens. Appl Phycol 2024; 5: 12-23.","DOI":"10.1080\/26388081.2024.2365467"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Kaiser WJ, Offermann MK. Apoptosis induced by the toll-like receptor adaptor TRIF is dependent on its receptor interacting protein homotypic interaction motif. J Immunol 2005; 174: 4942-4952.","DOI":"10.4049\/jimmunol.174.8.4942"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, <i>et al.<\/i> An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med 2003; 197: 1537-1549.","DOI":"10.1084\/jem.20021897"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell 2004; 5: 417-421.","DOI":"10.1016\/S1535-6108(04)00120-5"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Reinhardt HC, Schumacher B. The p53 network: Cellular and systemic DNA damage responses in aging and cancer. Trends Genet 2012; 28: 128-136.","DOI":"10.1016\/j.tig.2011.12.002"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Pidgeon GP, Barr MP, Harmey JH, Foley DA, Bouchier-Hayes DJ. Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. Br J Cancer 2001; 85: 273-278.","DOI":"10.1054\/bjoc.2001.1876"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Circu ML, Aw TY. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta 2012; 1823: 1767-1777.","DOI":"10.1016\/j.bbamcr.2012.06.019"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Bester AC, Roniger M, Oren YS, Im MM, Sarni D, Chaoat M, <i>et al.<\/i> Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011; 145: 435-446.","DOI":"10.1016\/j.cell.2011.03.044"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Musa M, Peri\u0107 M, Dib PB, Sobo\u010danec S, \u0160ari\u0107 A, Lovri\u0107 A, <i>et al.<\/i> Heat-induced longevity in budding yeast requires respiratory metabolism and glutathione recycling. Aging (Albany NY) 2018; 10: 2407-2427.","DOI":"10.18632\/aging.101560"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Vara J\u00c1F, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonz\u00e1lez-Bar\u00f3n M. PI3K\/Akt signalling pathway and cancer. Cancer Treat Rev 2004; 30: 193-204.","DOI":"10.1016\/j.ctrv.2003.07.007"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Fitton JH, Stringer DN, Karpiniec SS. Therapies from fucoidan: An update. Mar Drugs 2015; 13: 5920-5946.","DOI":"10.3390\/md13095920"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Guo Y, Xu T, Chai Y, Chen F. TGF-\u03b2 signaling in progression of oral cancer. Int J Mol Sci 2023; 24: 10263.","DOI":"10.3390\/ijms241210263"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Tominaga K, Suzuki HI. TGF-\u03b2 signaling in cellular senescence and aging-related pathology. Int J Mol Sci 2019; 20: 5002.","DOI":"10.3390\/ijms20205002"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Nicolas FJ, Hill CS. Attenuation of the TGF-\u03b2-Smad signaling pathway in pancreatic tumor cells confers resistance to TGF-\u03b2-induced growth arrest. Oncogene 2003; 22: 3698-3711.","DOI":"10.1038\/sj.onc.1206420"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Giarratana AO, Prendergast CM, Salvatore MM, Capaccione KM. TGF-\u03b2 signaling: Critical nexus of fibrogenesis and cancer. J Transl Med 2024; 22: 594.","DOI":"10.1186\/s12967-024-05411-4"},{"key":"45","unstructured":"45) Yang S, Gou J, Wang P, Luo L, Wei D. The lncRNA GUSB pseudogene 11 (GUSBP11) promotes the tumor growth and metastasis in lung adenocarcinoma. Altern Ther Health Med 2024; 30: 256-263."},{"key":"46","doi-asserted-by":"crossref","unstructured":"46) Barresi V, Cosentini I, Scuderi C, Napoli S, Di Bella V, Spampinato G, <i>et al.<\/i> Fusion transcripts of adjacent genes: New insights into the world of human complex transcripts in cancer. Int J Mol Sci 2019; 20: 5252.","DOI":"10.3390\/ijms20215252"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47) Ge J, Mu S, Xiao E, Tian G, Tao L, Li D. Expression, oncological and immunological characterizations of BZW1\/2 in pancreatic adenocarcinoma. Front Genet 2022; 13: 1002673.","DOI":"10.3389\/fgene.2022.1002673"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48) Zhang Q, Zhang Y, Sun S, Wang K, Qian J, Cui Z, <i>et al.<\/i> ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPAR\u03b1 pathway. Cell Death Dis 2021; 12: 15.","DOI":"10.1038\/s41419-020-03291-2"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49) Leys EJ, Crouse GF, Kellems RE. Dihydrofolate reductase gene expression in cultured mouse cells is regulated by transcript stabilization in the nucleus. J Cell Biol 1984; 99: 180-187.","DOI":"10.1083\/jcb.99.1.180"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50) Lasorella A, Uo T, Iavarone A. Id proteins at the cross-road of development and cancer. Oncogene 2001; 20: 8326-8333.","DOI":"10.1038\/sj.onc.1205093"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51) Li Q-L, Ito K, Sakakura C, Fukamachi H, Inoue K-i, Chi X-Z, <i>et al.<\/i> Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell 2002; 109: 113-124.","DOI":"10.1016\/S0092-8674(02)00690-6"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52) Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, <i>et al.<\/i> Regulation of cancer cell migration and bone metastasis by RANKL. Nature 2006; 440: 692-696.","DOI":"10.1038\/nature04524"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53) Schuller HM. Is cancer triggered by altered signalling of nicotinic acetylcholine receptors? Nat Rev Cancer 2009; 9: 195-205.","DOI":"10.1038\/nrc2590"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54) Ale MT, Meyer AS. Fucoidans from brown seaweeds: An update on structures, extraction techniques and use of enzymes as tools for structural elucidation. Rsc Adv 2013; 3: 8131-8141.","DOI":"10.1039\/C3RA23373A"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55) Bandopadhyay M, Bulbule A, Butti R, Chakraborty G, Ghorpade P, Ghosh P, <i>et al.<\/i> Osteopontin as a therapeutic target for cancer. Expert Opin Ther Targets 2014; 18: 883-895.","DOI":"10.1517\/14728222.2014.925447"},{"key":"56","doi-asserted-by":"crossref","unstructured":"56) Sodek J, Ganss B, McKee M. Osteopontin. Crit Rev Oral Biol Med 2000; 11: 279-303.","DOI":"10.1177\/10454411000110030101"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57) Lin Y, Qi X, Liu H, Xue K, Xu S, Tian Z. The anti-cancer effects of fucoidan: A review of both in vivo and in vitro investigations. Cancer Cell Int 2020; 20: 154.","DOI":"10.1186\/s12935-020-01233-8"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58) Sur S, Steele R, Ko BC, Zhang J, Ray RB. Long noncoding RNA ELDR promotes cell cycle progression in normal oral keratinocytes through induction of a CTCF-FOXM1-AURKA signaling axis. J Biol Chem 2022; 298: 101895.","DOI":"10.1016\/j.jbc.2022.101895"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59) Atashrazm F, Lowenthal RM, Woods GM, Holloway AF, Dickinson JL. Fucoidan and cancer: A multifunctional molecule with anti-tumor potential. Mar Drugs 2015; 13: 2327-2346.","DOI":"10.3390\/md13042327"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60) Zhang Z, Teruya K, Eto H, Shirahata S. Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. PLoS One 2011; 6: e27441.","DOI":"10.1371\/journal.pone.0027441"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61) Stupack DG, Puente XS, Boutsaboualoy S, Storgard CM, Cheresh DA. Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. J Cell Biol 2001; 155: 459-470.","DOI":"10.1083\/jcb.200106070"}],"container-title":["Dental Materials Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/dmj\/45\/4\/45_2025-314\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:47:55Z","timestamp":1784954875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/dmj\/45\/4\/45_2025-314\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,25]]},"references-count":61,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4012\/dmj.2025-314","relation":{},"ISSN":["0287-4547","1881-1361"],"issn-type":[{"value":"0287-4547","type":"print"},{"value":"1881-1361","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,25]]},"article-number":"2025-314"}}