{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:58:48Z","timestamp":1762063128970,"version":"build-2065373602"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian research agency","doi-asserted-by":"publisher","award":["P1-0140","P1-0175"],"award-info":[{"award-number":["P1-0140","P1-0175"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heavy metal ions can disrupt biological functions via multiple molecular mechanisms, including inhibition of enzymes. We investigate the interactions of human papain-like cysteine endopeptidases cathepsins L, K, and S with gallium and cerium ions, which are associated with medical applications. We compare these results with zinc and lead, which are known to inhibit thiol enzymes. We show that Ga3+, Ce3+, and Ce4+ ions inhibit all tested peptidases with inhibition constants in the low micromolar range (between 0.5 \u00b5M and 10 \u00b5M) which is comparable to Zn2+ ions, whereas inhibition constants of Pb2+ ions are one order of magnitude higher (30 \u00b5M to 150 \u00b5M). All tested ions are linear specific inhibitors of cathepsin L, but cathepsins K and S are inhibited by Ga3+, Ce3+, and Ce4+ ions via hyperbolic inhibition mechanisms. This indicates a mode of interaction different from that of Zn2+ and Pb2+ ions, which act as linear specific inhibitors of all peptidases. All ions also inhibit the degradation of insoluble elastin, which is a common target of these peptidases in various inflammatory diseases. Our results suggest that these ions and their compounds have the potential to be used as cysteine cathepsin inhibitors in vitro and possibly in vivo.<\/jats:p>","DOI":"10.3390\/ijms23168993","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T01:47:21Z","timestamp":1660528041000},"page":"8993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Kinetic Characterization of Cerium and Gallium Ions as Inhibitors of Cysteine Cathepsins L, K, and S"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1824-1649","authenticated-orcid":false,"given":"Marko","family":"Novinec","sequence":"first","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Primo\u017e","family":"Bembi\u010d","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica","family":"Jankovi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marija","family":"Kisilak","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1986-4840","authenticated-orcid":false,"given":"Jakob","family":"Kljun","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-4062","authenticated-orcid":false,"given":"Iztok","family":"Turel","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Chemical Technology, Department of Chemistry and Biochemistry, University of Ljubljana, Ve\u010dna pot 113, 1000 Ljubljana, Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1515\/bmc-2012-0054","article-title":"Papain-like Peptidases: Structure, Function, and Evolution","volume":"4","author":"Novinec","year":"2013","journal-title":"Biomol. Concepts"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbapap.2011.10.002","article-title":"Cysteine Cathepsins: From Structure, Function and Regulation to New Frontiers","volume":"1824","author":"Turk","year":"2012","journal-title":"Biochim. Biophys. Acta\u2014Proteins Proteom."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1073\/pnas.90.7.3063","article-title":"Two Distinct Gene Subfamilies within the Family of Cysteine Protease Genes","volume":"90","author":"Karrer","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1038\/s41467-020-15562-9","article-title":"Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and Its Immune Cross-Reactivity with SARS-CoV","volume":"11","author":"Ou","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cui, Z., Zeng, C., Huang, F., Yuan, F., Yan, J., Zhao, Y., Zhou, Y., Hankey, W., Jin, V.X., and Huang, J. (2022). Cas13d Knockdown of Lung Protease Ctsl Prevents and Treats SARS-CoV-2 Infection. Nat. Chem. Biol.","DOI":"10.1038\/s41589-022-01094-4"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"867928","DOI":"10.3389\/fchem.2022.867928","article-title":"Self-Masked Aldehyde Inhibitors of Human Cathepsin L Are Potent Anti-CoV-2 Agents","volume":"10","author":"Zhu","year":"2022","journal-title":"Front. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1126\/science.273.5279.1236","article-title":"Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency","volume":"273","author":"Gelb","year":"1996","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1074-7613(00)80249-6","article-title":"Essential Role for Cathepsin S in MHC Class II-Associated Invariant Chain Processing and Peptide Loading","volume":"4","author":"Riese","year":"1996","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"433","DOI":"10.3389\/fcell.2020.00433","article-title":"Cathepsin K: The Action in and Beyond Bone","volume":"8","author":"Dai","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/S2213-8587(19)30346-8","article-title":"Odanacatib for the Treatment of Postmenopausal Osteoporosis: Results of the LOFT Multicentre, Randomised, Double-Blind, Placebo-Controlled Trial and LOFT Extension Study","volume":"7","author":"McClung","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.2174\/0929867327666200330142432","article-title":"Osteoporosis: Mechanism, Molecular Target and Current Status on Drug Development","volume":"28","author":"Li","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"86","DOI":"10.7326\/M19-0675","article-title":"Disease-Modifying Effects of a Novel Cathepsin k Inhibitor in Osteoarthritis: A Randomized Controlled Trial","volume":"172","author":"Conaghan","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12931-020-01381-5","article-title":"Cathepsin S: Investigating an Old Player in Lung Disease Pathogenesis, Comorbidities, and Potential Therapeutics","volume":"21","author":"Brown","year":"2020","journal-title":"Respir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"112245","DOI":"10.1016\/j.biopha.2021.112245","article-title":"Therapeutic Potential of Targeting Cathepsin S in Pulmonary Fibrosis","volume":"145","author":"Yoo","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Moustakas, M. (2021). The Role of Metal Ions in Biology, Biochemistry and Medicine. Materials, 14.","DOI":"10.3390\/ma14030549"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Crichton, R.R. (2016). CHAPTER 1: Metal Toxicity\u2014An Introduction. Metal Chelation in Medicine, Royal Society of Chemistry.","DOI":"10.1039\/9781782623892-00001"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1126\/science.abf0529","article-title":"Copper Induces Cell Death by Targeting Lipoylated TCA Cycle Proteins","volume":"375","author":"Tsvetkov","year":"2022","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.abb.2004.09.011","article-title":"Cys-His Proteases Are among the Wired Proteins of the Cell","volume":"432","author":"Lockwood","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1039\/c2mt20156a","article-title":"Lysosomal Metal, Redox and Proton Cycles Influencing the CysHis Cathepsin Reaction","volume":"5","author":"Lockwood","year":"2013","journal-title":"Metallomics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10083","DOI":"10.1039\/D1CC03563K","article-title":"Zinc2+ Ion Inhibits SARS-CoV-2 Main Protease and Viral Replication In Vitro","volume":"57","author":"Panchariya","year":"2021","journal-title":"Chem. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1080\/14756366.2022.2108417","article-title":"Zinc Pyrithione Is a Potent Inhibitor of PLPro and Cathepsin L Enzymes with Ex Vivo Inhibition of SARS-CoV-2 Entry and Replication","volume":"37","author":"Kladnik","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_22","unstructured":"Meisenheimer, M., Saenko, Y., and Eppard, E. (2019). Gallium-68: Radiolabeling of Radiopharmaceuticals for PET Imaging\u2014A Lot to Consider. Medical Isotopes, IntechOpen."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1177\/00220345940730091101","article-title":"Cytotoxicity of Gallium and Indium Ions Compared with Mercuric Ion","volume":"73","author":"Chandler","year":"1994","journal-title":"J. Dent. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.btre.2017.11.008","article-title":"Synthesis and Biomedical Applications of Cerium Oxide Nanoparticles\u2014A Review","volume":"17","author":"Rajeshkumar","year":"2018","journal-title":"Biotechnol. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Nelson, B.C., Johnson, M.E., Walker, M.L., Riley, K.R., and Sims, C.M. (2016). Antioxidant Cerium Oxide Nanoparticles in Biology and Medicine. Antioxidants, 5.","DOI":"10.3390\/antiox5020015"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.tiv.2017.09.024","article-title":"Effects of the Rare Elements Lanthanum and Cerium on the Growth of Colorectal and Hepatic Cancer Cell Lines","volume":"46","author":"Benedetto","year":"2018","journal-title":"Toxicol. Vitr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.1166\/jnn.2019.17035","article-title":"In-Vitro Cytotoxicity and Oxidative Stress Induced by Cerium Aminoclay and Cerium Oxide Nanoparticles in Human Skin Keratinocyte Cells","volume":"19","author":"Ngoc","year":"2019","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.3390\/ijms14023065","article-title":"Cytotoxicity and Genotoxicity of Ceria Nanoparticles on Different Cell Lines in Vitro","volume":"14","author":"Monaco","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"696","DOI":"10.3109\/17435390.2014.968889","article-title":"DNA Damage and Oxidative Stress Induced by CeO2 Nanoparticles in Human Dermal Fibroblasts: Evidence of a Clastogenic Effect as a Mechanism of Genotoxicity","volume":"9","author":"Benameur","year":"2015","journal-title":"Nanotoxicology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.1002\/anie.201007100","article-title":"Farewell to the HSAB Treatment of Ambident Reactivity","volume":"50","author":"Mayr","year":"2011","journal-title":"Angew. Chemie Int. Ed."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1021\/tx2003257","article-title":"Application of the Hard and Soft, Acids and Bases (HSAB) Theory to Toxicant\u2014Target Interactions","volume":"25","author":"LoPachin","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13959","DOI":"10.1039\/c3cp51134k","article-title":"How Reliable Is the Hard\u2013Soft Acid\u2013Base Principle? An Assessment from Numerical Simulations of Electron Transfer Energies","volume":"15","author":"Ayers","year":"2013","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"181106","DOI":"10.1063\/1.4805083","article-title":"Communication: A Case Where the Hard\/Soft Acid\/Base Principle Holds Regardless of Acid\/Base Strength","volume":"138","author":"Ayers","year":"2013","journal-title":"J. Chem. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0010-8545(90)85016-L","article-title":"Hard and Soft Acids and Bases\u2014The Evolution of a Chemical Concept","volume":"100","author":"Pearson","year":"1990","journal-title":"Coord. Chem. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0040-6031(73)87017-0","article-title":"A Thermodynamic Study of the Complexation Reaction for Some Amino Acids with Cerium(III) and Yttrium(III)","volume":"7","author":"Sekhon","year":"1973","journal-title":"Thermochim. Acta"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2830","DOI":"10.1021\/je101329d","article-title":"Complex Formation of the Cerium(IV) Ion with Glycyl-Glycine at Different Ionic Strengths","volume":"56","author":"Kiani","year":"2011","journal-title":"J. Chem. Eng. Data"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ab.2007.07.008","article-title":"Rapid Determination of Enzyme Kinetics from Fluorescence: Overcoming the Inner Filter Effect","volume":"371","author":"Palmier","year":"2007","journal-title":"Anal. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jlumin.2016.08.024","article-title":"Synthesis, Structure and Artificial Protease Activities of Two Cerium (III) Complexes","volume":"180","author":"Ghose","year":"2016","journal-title":"J. Lumin."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1002\/cbic.201500041","article-title":"Tuning Cerium(IV)-Assisted Hydrolysis of Phosphatidylcholine Liposomes under Mildly Acidic and Neutral Conditions","volume":"16","author":"Williams","year":"2015","journal-title":"ChemBioChem"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1432-1033.1981.tb05570.x","article-title":"The Specific Velocity Plot: A Graphical Method for Determining Inhibition Parameters for Both Linear and Hyperbolic Enzyme Inhibitors","volume":"119","author":"Baici","year":"1981","journal-title":"Eur. J. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1039\/tf9534900696","article-title":"Analytical Description of the Effects of Modifiers and of Enzyme Multivalency upon the Steady State Catalyzed Reaction Rate","volume":"49","author":"Botts","year":"1953","journal-title":"Trans. Faraday Soc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1002\/pmic.201400460","article-title":"Fast Profiling of Protease Specificity Reveals Similar Substrate Specificities for Cathepsins K, L and S","volume":"15","author":"Vidmar","year":"2015","journal-title":"Proteomics"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3287","DOI":"10.1038\/ncomms4287","article-title":"A Novel Allosteric Mechanism in the Cysteine Peptidase Cathepsin K Discovered by Computational Methods","volume":"5","author":"Novinec","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Novinec, M., Lenar\u010di\u010d, B., and Baici, A. (2014). Probing the Activity Modification Space of the Cysteine Peptidase Cathepsin K with Novel Allosteric Modifiers. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106642"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"105213","DOI":"10.1016\/j.bioorg.2021.105213","article-title":"Synthesis and Kinetic Characterization of Hyperbolic Inhibitors of Human Cathepsins K and S Based on a Succinimide Scaffold","volume":"115","author":"Ciber","year":"2021","journal-title":"Bioorg. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1111\/j.1742-4658.2010.07663.x","article-title":"Paradoxical Interactions between Modifiers and Elastase-2","volume":"277","author":"Schenker","year":"2010","journal-title":"FEBS J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1042\/bj2330925","article-title":"Elastinolytic activity of human cathepsin L","volume":"233","author":"Mason","year":"1986","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"9682","DOI":"10.1038\/s41598-019-45918-1","article-title":"Elastolytic Activity of Cysteine Cathepsins K, S, and V Promotes Vascular Calcification","volume":"9","author":"Andrault","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1084\/jem.192.6.789","article-title":"Regulation of Elastinolytic Cysteine Proteinase Activity in Normal and Cathepsin K-Deficient Human Macrophages","volume":"192","author":"Punturieri","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3849","DOI":"10.1073\/pnas.92.9.3849","article-title":"Pericellular Mobilization of the Tissue-Destructive Cysteine Proteinases, Cathepsins B, L, and S, by Human Monocyte-Derived Macrophages","volume":"92","author":"Reddy","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7893","DOI":"10.1074\/jbc.M610107200","article-title":"Interaction between Human Cathepsins K, L, and S and Elastins: Mechanism of Elastinolysis and Inhibition by Macromolecular Inhibitors","volume":"282","author":"Novinec","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1042\/BJ20140809","article-title":"Structural Requirements for the Collagenase and Elastase Activity of Cathepsin K and Its Selective Inhibition by an Exosite Inhibitor","volume":"465","author":"Sharma","year":"2015","journal-title":"Biochem. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1042\/BCJ20190847","article-title":"Characterization of Cathepsin S Exosites That Govern Its Elastolytic Activity","volume":"477","author":"Andrault","year":"2020","journal-title":"Biochem. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bmcl.2007.12.047","article-title":"The Discovery of Odanacatib (MK-0822), a Selective Inhibitor of Cathepsin K","volume":"18","author":"Gauthier","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1038\/s41598-017-01894-y","article-title":"Cathepsin S Inhibition Combines Control of Systemic and Peripheral Pathomechanisms of Autoimmune Tissue Injury","volume":"7","author":"Tato","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1002\/ejic.201600986","article-title":"Thirty Years of the Drug Candidate NAMI-A and the Myths in the Field of Ruthenium Anticancer Compounds: A Personal Perspective","volume":"2017","author":"Alessio","year":"2017","journal-title":"Eur. J. Inorg. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jmb.2008.07.038","article-title":"The Crystal and Molecular Structures of a Cathepsin K:Chondroitin Sulfate Complex","volume":"383","author":"Li","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Novinec, M. (2017). Computational Investigation of Conformational Variability and Allostery in Cathepsin K and Other Related Peptidases. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182387"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Reed, K., Bush, N., Burns, Z., Doherty, G., Foley, T., Milone, M., Maki, K.L., and Cromer, M. (2019). Modeling the Kinetic Behavior of Reactive Oxygen Species with Cerium Dioxide Nanoparticles. Biomolecules, 9.","DOI":"10.3390\/biom9090447"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1515\/zna-1992-0908","article-title":"Thermodynamic Study of Ce4+\/Ce3+ Redox Reaction in Aqueous Solutions at Elevated Temperatures: 1. Reduction Potential and Hydrolysis Equilibria of Ce4+ in HClO4 Solutions","volume":"47","author":"Bilal","year":"1992","journal-title":"Z. Naturforsch.\u2014Sect. A J. Phys. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Brown, P.L., and Ekberg, C. (2016). Theory. Hydrolysis of Metal Ions, Wiley Online Books.","DOI":"10.1002\/9783527656189"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jtemb.2010.03.001","article-title":"Measurement of Cerium in Human Breast Milk and Blood Samples","volume":"24","author":"Trasobares","year":"2010","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1007\/BF00795460","article-title":"The Topography of Gallium in the Healthy Human Body","volume":"62","author":"Belozerov","year":"1966","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4328","DOI":"10.1111\/febs.13499","article-title":"Human Cathepsin L, a Papain-like Collagenase without Proline Specificity","volume":"282","author":"Novinec","year":"2015","journal-title":"FEBS J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:07:40Z","timestamp":1760141260000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/8993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,12]]},"references-count":64,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23168993"],"URL":"https:\/\/doi.org\/10.3390\/ijms23168993","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2022,8,12]]}}}