{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T15:13:29Z","timestamp":1789312409248,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T00:00:00Z","timestamp":1634342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The safety of food additives E407 and E407a has raised concerns in the scientific community. Thus, this study aims to assess the local and systemic toxic effects of the common food additive E407a in rats orally exposed to it for two weeks. Complex evaluations of the effects of semi-refined carrageenan (E407a) on rats upon oral exposure were performed. Local effects of E407a on the intestine were analyzed using routine histological stains and CD68 immunostaining. Furthermore, circulating levels of inflammatory markers were assessed. A fluorescent probe O1O (2- (2\u2032-OH-phenyl)-5-phenyl-1,3-oxazole) was used for evaluating the state of leukocyte cell membranes. Cell death modes of leukocytes were analyzed by flow cytometry using Annexin V and 7-aminoactinomycin D staining. Oral administration of the common food additive E407a was found to be associated with altered small and large intestinal morphology, infiltration of the lamina propria in the small intestine with macrophages (CD68+ cells), high systemic levels of inflammation markers, and changes in the lipid order of the phospholipid bilayer in the cell membranes of leukocytes, alongside the activation of their apoptosis. Our findings suggest that oral exposure to E407a through rats results in the development of intestinal inflammation.<\/jats:p>","DOI":"10.3390\/ijms222011178","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:05:47Z","timestamp":1634511947000},"page":"11178","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Experimental Evaluation of Food-Grade Semi-Refined Carrageenan Toxicity"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-5425","authenticated-orcid":false,"given":"Denys","family":"Pogozhykh","sequence":"first","affiliation":[{"name":"Clinic for Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevgen","family":"Posokhov","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, 6 Trinklera st, 61022 Kharkiv, Ukraine"},{"name":"Department of Organic Chemistry, Biochemistry, Paints and Coatings, The National Technical University \u201cKharkiv Polytechnic Institute\u201d, 2 Kyrpychova st, 61000 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy","family":"Myasoedov","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Gubina-Vakulyck","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetyana","family":"Chumachenko","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Kharkiv National Medical University, 12 Trinklera st, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8870-3450","authenticated-orcid":false,"given":"Oleksandr","family":"Knigavko","sequence":"additional","affiliation":[{"name":"Department of Urology, Nephrology and Andrology, Kharkiv National Medical University, 195 Moskovsky ave, 61002 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Polikarpova","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliia","family":"Kalashnyk-Vakulenko","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ketino","family":"Sharashydze","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Kharkiv National Medical University, 4 Malinovskogo st, 61052 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Nakonechna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Prokopyuk","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, 6 Trinklera st, 61022 Kharkiv, Ukraine"},{"name":"Department of Cryobiology of the Reproductive System, Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, 23 Pereyaslavskaya st, 61015 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anatolii","family":"Onishchenko","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, 6 Trinklera st, 61022 Kharkiv, Ukraine"},{"name":"Department of Biochemistry, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Tkachenko","sequence":"additional","affiliation":[{"name":"Research Institute of Experimental and Clinical Medicine, Kharkiv National Medical University, 6 Trinklera st, 61022 Kharkiv, Ukraine"},{"name":"Department of Biochemistry, Kharkiv National Medical University, 4 Nauky ave, 61022 Kharkiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.17221\/6758-VETMED","article-title":"Carrageenan: A review","volume":"58","author":"Necas","year":"2013","journal-title":"Vet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Besednova, N., Zaporozhets, T., Kuznetsova, T., Makarenkova, I., Fedyanina, L., Kryzhanovsky, S., Malyarenko, O., and Ermakova, S. (2019). Metabolites of Seaweeds as Potential Agents for the Prevention and Therapy of Influenza Infection. Mar. Drugs, 17.","DOI":"10.3390\/md17060373"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Besednova, N.N., Zvyagintseva, T.N., Kuznetsova, T.A., Makarenkova, I.D., Smolina, T.P., Fedyanina, L.N., Kryzhanovsky, S.P., and Zaporozhets, T.S. (2019). Marine Algae Metabolites as Promising Therapeutics for the Prevention and Treatment of HIV\/AIDS. Metabolites, 9.","DOI":"10.3390\/metabo9050087"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yermak, I.M., Mischchenko, N.P., Davydova, V.N., Glazunov, V.P., Tarbeeva, D.V., Kravchenko, A.O., Pimenova, E.A., and Sorokina, I.V. (2017). Carrageenans-Sulfated Polysaccharides from Red Seaweeds as Matrices for the Inclusion of Echinochrome. Mar. Drugs, 15.","DOI":"10.3390\/md15110337"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8158315","DOI":"10.1155\/2017\/8158315","article-title":"Carrageenan Based Bionanocomposites as Drug Delivery Tool with Special Emphasis on the Influence of Ferromagnetic Nanoparticles","volume":"2017","author":"Saba","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.3390\/md8092435","article-title":"Marine polysaccharides in pharmaceutical applications: An overview","volume":"8","author":"Laurienzo","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0924-2244(02)00066-3","article-title":"1H and 13C high resolution NMR spectroscopy of carrageenans: Application in research and industry","volume":"13","author":"Knutsen","year":"2002","journal-title":"Trends Food Sci. Technol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Borsani, B., De Santis, R., Perico, V., Penagini, F., Pendezza, E., Dilillo, D., Bosetti, A., Zuccotti, G.V., and D\u2019Auria, E. (2021). The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand?. Nutrients, 13.","DOI":"10.3390\/nu13103402"},{"key":"ref_9","unstructured":"Hotchkiss, S., Brooks, M., Campbell, R., Philp, K., and Trius, A. (2016). Carrageenans: Sources and extraction methods, molecular structure, bioactive properties and health effects. Use Carrageenan Food, Nova Science Publishers, Inc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1581746","DOI":"10.1155\/2018\/1581746","article-title":"Overview on untargeted methods to combat food frauds: A focus on fishery products","volume":"2018","author":"Fiorino","year":"2018","journal-title":"J. Food Qual."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"244","DOI":"10.3109\/10408444.2013.861798","article-title":"Food additive carrageenan: Part II: A critical review of carrageenan in vivo safety studies","volume":"44","author":"Weiner","year":"2014","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1016\/j.jaci.2015.08.048","article-title":"The common food additive carrageenan and the alpha-gal epitope","volume":"136","author":"Tobacman","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1289\/ehp.01109983","article-title":"Review of harmful gastrointestinal effects of carrageenan in animal experiments","volume":"109","author":"Tobacman","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.fct.2016.07.006","article-title":"Effects of carrageenan on cell permeability, cytotoxicity, and cytokine gene expression in human intestinal and hepatic cell lines","volume":"96","author":"McKim","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1111\/1541-4337.12790","article-title":"Food-grade carrageenans and their implications in health and disease","volume":"20","author":"Liu","year":"2021","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s40168-020-00996-6","article-title":"Direct impact of commonly used dietary emulsifiers on human gut microbiota","volume":"9","author":"Naimi","year":"2021","journal-title":"Microbiome"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104707","DOI":"10.1016\/j.jff.2021.104707","article-title":"Effect of \u03ba-carrageenan on glucolipid metabolism and gut microbiota in high-fat diet-fed mice","volume":"86","author":"Wang","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1600545","DOI":"10.1002\/mnfr.201600545","article-title":"Digestive fate of dietary carrageenan: Evidence of interference with digestive proteolysis and disruption of gut epithelial function","volume":"61","author":"Fahoum","year":"2017","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8634865","DOI":"10.1155\/2017\/8634865","article-title":"kappa-Carrageenan Enhances Lipopolysaccharide-Induced Interleukin-8 Secretion by Stimulating the Bcl10-NF-kappaB Pathway in HT-29 Cells and Aggravates, C. freundii-Induced Inflammation in Mice","volume":"2017","author":"Wu","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Campmans-Kuijpers, M.J.E., and Dijkstra, G. (2021). Food and Food Groups in Inflammatory Bowel Disease (IBD): The Design of the Groningen Anti-Inflammatory Diet (GrAID). Nutrients, 13.","DOI":"10.3390\/nu13041067"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Marion-Letellier, R., Amamou, A., Savoye, G., and Ghosh, S. (2019). Inflammatory Bowel Diseases and Food Additives: To Add Fuel on the Flames!. Nutrients, 11.","DOI":"10.3390\/nu11051111"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1128\/IAI.67.7.3284-3289.1999","article-title":"Carrageenan primes leukocytes to enhance lipopolysaccharide-induced tumor necrosis factor alpha production","volume":"67","author":"Ogata","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_23","first-page":"199","article-title":"Derivatives of 2, 5-diaryl-1, 3-oxazole and 2, 5-diaryl-1, 3, 4-oxadiazole as environment-sensitive fluorescent probes for studies of biological membranes","volume":"2018","author":"Posokhov","year":"2017","journal-title":"Rev. Fluoresc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1039\/b107255m","article-title":"Radiationless deactivation of the excited phototautomer form and molecular structure of ESIPT-compounds","volume":"1","author":"Doroshenko","year":"2002","journal-title":"Photochem. Photobiol. Sci."},{"key":"ref_25","first-page":"388","article-title":"Intramolecular proton-transfer reaction in an excited state in a series of ortho-hydroxy derivatives of 2, 5-diaryloxazole","volume":"31","author":"Doroshenko","year":"1997","journal-title":"High Energy Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bpc.2018.01.005","article-title":"Location of fluorescent probes (2\u2019-hydroxy derivatives of 2,5-diaryl-1,3-oxazole) in lipid membrane studied by fluorescence spectroscopy and molecular dynamics simulation","volume":"235","author":"Posokhov","year":"2018","journal-title":"Biophys. Chem."},{"key":"ref_27","first-page":"77","article-title":"O-6-methylguanine-DNA methyltransferase (MGMT) overexpression in small intestinal mucosa in experimental carrageenan-induced enteritis","volume":"21","author":"Tkachenko","year":"2018","journal-title":"Malays. J. Biochem. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00580-015-2102-3","article-title":"Damage and regeneration of small intestinal enterocytes under the influence of carrageenan induces chronic enteritis","volume":"24","author":"Gorbach","year":"2015","journal-title":"Comp. Clin. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.carbpol.2009.01.020","article-title":"Carrageenans: Biological properties, chemical modifications and structural analysis\u2014A review","volume":"77","author":"Campo","year":"2009","journal-title":"Carbohydr. Polym."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10550","DOI":"10.1074\/jbc.M708833200","article-title":"Toll-like receptor 4 mediates induction of the Bcl10-NFkappaB-interleukin-8 inflammatory pathway by carrageenan in human intestinal epithelial cells","volume":"283","author":"Bhattacharyya","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1039\/C8FO01282B","article-title":"Comment on \u201cRevisiting the carrageenan controversy: Do we really understand the digestive fate and safety of carrageenan in our foods?\u201d by S. David, C. S. Levi, L. Fahoum, Y. Ungar, E. G. Meyron-Holtz, A. Shpigelman and U. Lesmes, Food Funct., 2018, 9, 1344\u20131352","volume":"10","author":"Weiner","year":"2019","journal-title":"Food Funct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.fct.2014.12.022","article-title":"An infant formula toxicity and toxicokinetic feeding study on carrageenan in preweaning piglets with special attention to the immune system and gastrointestinal tract","volume":"77","author":"Weiner","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.fct.2006.07.033","article-title":"A 90-day dietary study on kappa carrageenan with emphasis on the gastrointestinal tract","volume":"45","author":"Weiner","year":"2007","journal-title":"Food Chem. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1080\/10408398.2018.1481822","article-title":"Clarifying the confusion between poligeenan, degraded carrageenan, and carrageenan: A review of the chemistry, nomenclature, and in vivo toxicology by the oral route","volume":"59","author":"McKim","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1039\/C7FO01721A","article-title":"Revisiting the carrageenan controversy: Do we really understand the digestive fate and safety of carrageenan in our foods?","volume":"9","author":"David","year":"2018","journal-title":"Food Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0268-005X(96)80040-3","article-title":"In-vitro gastric stability of carrageenan","volume":"10","author":"Capron","year":"1996","journal-title":"Food Hydrocoll."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6188","DOI":"10.1021\/bi00018a023","article-title":"Hydration and order in lipid bilayers","volume":"34","author":"Ho","year":"1995","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S0006-3495(03)74541-X","article-title":"Lipid membrane polarity profiles by high-field EPR","volume":"85","author":"Kurad","year":"2003","journal-title":"Biophys. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1016\/S0006-3495(03)74918-2","article-title":"Intramembrane polarity by electron spin echo spectroscopy of labeled lipids","volume":"84","author":"Bartucci","year":"2003","journal-title":"Biophys. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0006-3495(01)75692-5","article-title":"Structural properties of a highly polyunsaturated lipid bilayer from molecular dynamics simulations","volume":"81","author":"Saiz","year":"2001","journal-title":"Biophys. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/S1554-4516(06)05013-7","article-title":"Transmembrane polarity profile of lipid membranes","volume":"5","year":"2006","journal-title":"Adv. Planar Lipid Bilayers Liposomes"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1016\/j.bbamem.2012.07.017","article-title":"Detection of apoptosis through the lipid order of the outer plasma membrane leaflet","volume":"1818","author":"Darwich","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1016\/j.bbamem.2017.08.002","article-title":"Caspase-3 activation decreases lipid order in the outer plasma membrane leaflet during apoptosis: A fluorescent probe study","volume":"1859","author":"Pyrshev","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_44","first-page":"67","article-title":"Carrageenan induces cell death in rats blood","volume":"4","author":"Kopanytsia","year":"2018","journal-title":"Int. J. Med. Med. Res."},{"key":"ref_45","first-page":"169","article-title":"Common food additive E407a affects BCL-2 expression in lymphocytes in vitro","volume":"29","author":"Tkachenko","year":"2019","journal-title":"Studia Univ. \"Vasile Goldis\" Arad. Ser. Stiintele Vietii Life Sci. Ser."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"397642","DOI":"10.1155\/2013\/397642","article-title":"Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice","volume":"2013","author":"Bhattacharyya","year":"2013","journal-title":"Mediat. Inflamm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/NHA-170023","article-title":"A randomized trial of the effects of the no-carrageenan diet on ulcerative colitis disease activity","volume":"4","author":"Bhattacharyya","year":"2017","journal-title":"Nutr. Healthy Aging"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/modpathol.2010.207","article-title":"Fibrolamellar carcinomas are positive for CD68","volume":"24","author":"Ross","year":"2011","journal-title":"Mod. Pathol."},{"key":"ref_49","first-page":"138","article-title":"Experience of using index of middle molecules in blood to diagnose nephrological diseases among children","volume":"3","author":"Gabriyelyan","year":"1984","journal-title":"Lab. Delo"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/BF02522792","article-title":"Proton phototransfer in a series of ortho-hydroxy derivatives of 2, 5-diaryl-1, 3-oxazole and 2, 5-diaryl-1, 3, 4-oxadiazole in polystyrene films","volume":"35","author":"Doroshenko","year":"1999","journal-title":"Theor. Exp. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1039\/b507447a","article-title":"The problem of self-calibration of fluorescence signal in microscale sensor systems","volume":"5","author":"Demchenko","year":"2005","journal-title":"Lab Chip"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0091-679X(08)60429-X","article-title":"Ratio imaging: Practical considerations for measuring intracellular calcium and pH in living tissue","volume":"56","author":"Silver","year":"1998","journal-title":"Methods Cell Biol."},{"key":"ref_53","unstructured":"Dobretsov, G. (1989). Fluorescence Probes in Cell, Membrane and Lipoprotein Investigations, Nauka. (In Russian)."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11178\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:16:14Z","timestamp":1760166974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/20\/11178"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,16]]},"references-count":53,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["ijms222011178"],"URL":"https:\/\/doi.org\/10.3390\/ijms222011178","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,16]]}}}