{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:12:45Z","timestamp":1793326365554,"version":"4.5.0"},"reference-count":206,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nutr Metab Insights"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>Obesity is a complex metabolic disorder associated with chronic low-grade inflammation, insulin resistance, and heightened risk of comorbidities such as cardiovascular diseases and type 2 diabetes mellitus (T2DM). The Cluster of Differentiation 44 (CD44), a transmembrane glycoprotein, interacts with hyaluronic acid (HA), a major extracellular matrix (ECM) component, to regulate adipogenesis, immune cell infiltration, and metabolic dysfunction. Dysregulation of the CD44-HA signalling axis promotes adipose tissue hypertrophy, macrophage infiltration, and activation of pro-inflammatory pathways, including nuclear factor-kappa B (NF-\u03baB) and mitogen-activated protein kinases (MAPKs), which further aggravate metabolic disturbances. This review provides a comprehensive analysis of CD44-HA signalling in the pathophysiology of obesity and evaluates therapeutic strategies targeting this axis. Small-molecule inhibitors, such as CD44 antagonists and hyaluronan biosynthesis modulators (eg, 4-methylumbelliferone), offer advantages in synthesis, bioavailability, and cost-effectiveness, but face challenges related to limited specificity, systemic toxicity, and potential resistance. In contrast, Nanobioconjugates engineered nanoparticles conjugated with biomolecules such as HA enable targeted delivery to CD44-overexpressing adipose tissues, enhance therapeutic efficacy, prolong drug release, and minimize off-target effects. Examples include lipid-based nanoparticles, polymer-based nanocarriers, and HA-functionalized systems, all of which show promise in preclinical models of obesity. Comparative analysis underscores the superior specificity and bioavailability of nanobioconjugates, though issues of large-scale production, immunogenicity, and regulatory approval remain. Combining nanobioconjugates with small molecules may optimize treatment outcomes by leveraging synergistic mechanisms. Emerging strategies including high-affinity HA ligands, monoclonal antibodies, RNA-based therapeutics, and artificial intelligence (AI) guided drug design, offering new opportunities for precision obesity management. Future directions highlight the importance of personalized and combinatorial therapies, supported by biomarker profiling and gene editing technologies such as CRISPR, to overcome current limitations in CD44-HA-targeted interventions.<\/jats:p>","DOI":"10.1177\/11786388251408961","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:47:28Z","timestamp":1767779248000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting CD44-Hyaluronic Acid Signalling in Obesity Treatment: Insights from Small Molecules and Nanobioconjugates"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1129-1785","authenticated-orcid":false,"given":"Daniel Ejim","family":"Uti","sequence":"first","affiliation":[{"name":"Department of Research and Publications, Kampala International University, Uganda"},{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Federal University of Health Sciences, Otukpo, Benue State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilson Achu","family":"Omang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Health Technology, Calabar, Cross River State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther Ugo","family":"Alum","sequence":"additional","affiliation":[{"name":"Department of Research and Publications, Kampala International University, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Okechukwu Paul-Chima","family":"Ugwu","sequence":"additional","affiliation":[{"name":"Department of Research and Publications, Kampala International University, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret Amieibi","family":"Wokoma","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rowland Inalegwu","family":"Oplekwu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, Federal University of Allied Health Sciences, Enugu, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Item Justin","family":"Atangwho","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godwin Eneji","family":"Egbung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108549"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.obmed.2025.100585"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00112"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.01.012"},{"key":"e_1_3_3_6_2","unstructured":"World Health Orgainization. Obesity. https:\/\/www.who.int\/health-topics\/obesity"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.7861\/clinmed.2023-0168"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqac031"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13795"},{"key":"e_1_3_3_10_2","volume-title":"StatPearls","author":"Parmar RM","year":"2025","unstructured":"Parmar RM, Can AS. Physiology, appetite and weight regulation. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-022-00741-z"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2021.114723"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S275898"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103264"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajcnut.2023.05.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/oby.24060"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnint.2022.798995"},{"key":"e_1_3_3_18_2","volume-title":"Endotext","author":"Feingold KR","year":"2000","unstructured":"Feingold KR, In G, M, Obesity and dyslipidemia. In: Feingold KR, Anawalt B, Blackman MR, et al., eds. Endotext. MDText.com, Inc; 2000."},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21238985"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11050844"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0173"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45110570"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.999001"},{"key":"e_1_3_3_24_2","first-page":"1474","article-title":"The firmicutes\/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients?","volume":"12","author":"Magne F","year":"2020","unstructured":"Magne F, Gotteland M, Gauthier L, et al. The firmicutes\/bacteroidetes ratio: a relevant marker of gut dysbiosis in obese patients? Nutrition. 2020;12:1474.","journal-title":"Nutrition"},{"key":"e_1_3_3_25_2","first-page":"2652","article-title":"Genes involved in susceptibility to obesity and emotional eating behavior in a Romanian population","volume":"16","author":"Vranceanu M","year":"2024","unstructured":"Vranceanu M, Filip L, Heghe\u0219 S-C, et al. Genes involved in susceptibility to obesity and emotional eating behavior in a Romanian population. Nutrition. 2024;16:2652.","journal-title":"Nutrition"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.endmts.2024.100205"},{"key":"e_1_3_3_27_2","article-title":"Modulation of lipogenesis by Tetracarpidium conophorum nuts via SREBP-1\/ACCA-1\/FASN inhibition in monosodium-glutamate-induced obesity in rats","volume":"20","author":"Umoru GU","year":"2025","unstructured":"Umoru GU, Atangwho IJ, David-Oku E, et al. Modulation of lipogenesis by Tetracarpidium conophorum nuts via SREBP-1\/ACCA-1\/FASN inhibition in monosodium-glutamate-induced obesity in rats. Nat Prod Commun. 2025;20:1934578X251344035.","journal-title":"Nat Prod Commun"},{"key":"e_1_3_3_28_2","article-title":"Buchholzia coriacea leaves attenuated dyslipidemia and oxidative stress in hyperlipidemic rats and its potential targets in silico","volume":"05","author":"Uti DE","year":"2023","unstructured":"Uti DE, Ibiam UA, Omang WA, et al. Buchholzia coriacea leaves attenuated dyslipidemia and oxidative stress in hyperlipidemic rats and its potential targets in silico. Pharm Front. 2023;05:e141-e152.","journal-title":"Pharm Front"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph21060757"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/ijpo.13032"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pedhc.2019.10.002"},{"key":"e_1_3_3_32_2","volume-title":"StatPearls","author":"Ginsburg BM","year":"2025","unstructured":"Ginsburg BM, Daley SF, Sheer AJ. Overcoming stigma and bias in obesity management. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087286"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.12.016"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c02434"},{"key":"e_1_3_3_36_2","first-page":"67","article-title":"Deletion of CD44 promotes adipogenesis and insulin signalling in adipocytes","volume":"64","author":"Weng X","year":"2021","unstructured":"Weng X, Hennayake CK, Kang L. Deletion of CD44 promotes adipogenesis and insulin signalling in adipocytes. Diabetologia. 2021;64:67-68.","journal-title":"Diabetologia"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.07.002"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.34172\/apb.2021.050"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00487"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-024-02549-9"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2024.10.005"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2022.02.002"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01607"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.obpill.2024.100108"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70086"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20194888"},{"key":"e_1_3_3_47_2","first-page":"2087","article-title":"Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential","volume":"18","author":"Liu Z","year":"2024","unstructured":"Liu Z, Hou P, Fang J, et al. Hyaluronic acid metabolism and chemotherapy resistance: recent advances and therapeutic potential. Mol Oncol. 2024;18:2087-2106.","journal-title":"Mol Oncol"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00182"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115812"},{"key":"e_1_3_3_50_2","first-page":"117","article-title":"A decrease in CD44 on cell surfaces (MKN-45 cell line) after RELA knockout using CRISPR\/Cas9","volume":"11","author":"Karimi S","year":"2023","unstructured":"Karimi S, Salmani S, Alizadeh A, Rezakhani L, Saltanatpour Z, Ghasemi S. A decrease in CD44 on cell surfaces (MKN-45 cell line) after RELA knockout using CRISPR\/Cas9. Int J Mol Cell Med. 2023;11:117-126.","journal-title":"Int J Mol Cell Med"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-24-0079"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-019-6055-9"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114104"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-015-3603-y"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00215.2019"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-060721-092930"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-022-10046-2"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.625331"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155262"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03412-z"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c08770"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2022.02.015"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26113278"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01998"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S430877"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/s11671-025-04248-0"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11121850"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010252"},{"key":"e_1_3_3_69_2","first-page":"231","volume-title":"Advances in Cancer Research","author":"Orian-Rousseau V","unstructured":"Orian-Rousseau V, Sleeman J. Chapter nine - CD44 is a multidomain signaling platform that integrates extracellular matrix cues with growth factor and cytokine signals. In: Simpson MA, Heldin P eds. Advances in Cancer Research. Academic Press; 2014:231-254."},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15205041"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1026810"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.607483"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2023.12.005"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-024-02212-y"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.34133\/cbsystems.0129"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-020-09909-3"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129167"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4481"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-016-0379-9"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48878-8"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00043"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom10111525"},{"key":"e_1_3_3_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2023.tb00254.x"},{"key":"e_1_3_3_84_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052756"},{"key":"e_1_3_3_85_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2252516"},{"key":"e_1_3_3_86_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1365156"},{"key":"e_1_3_3_87_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00068"},{"key":"e_1_3_3_88_2","doi-asserted-by":"publisher","DOI":"10.5935\/scd1984-8773.2021130006"},{"key":"e_1_3_3_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.02.006"},{"key":"e_1_3_3_90_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-021-01559-z"},{"key":"e_1_3_3_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2025.e41895"},{"key":"e_1_3_3_92_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.2c00012"},{"key":"e_1_3_3_93_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2025.115074"},{"key":"e_1_3_3_94_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-018-0605-5"},{"key":"e_1_3_3_95_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1014778"},{"key":"e_1_3_3_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2023.110691"},{"key":"e_1_3_3_97_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00791-9"},{"key":"e_1_3_3_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2017.12.001"},{"key":"e_1_3_3_99_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316903"},{"key":"e_1_3_3_100_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.116161"},{"key":"e_1_3_3_101_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12123798"},{"key":"e_1_3_3_102_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00379.2020"},{"key":"e_1_3_3_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2024.100644"},{"key":"e_1_3_3_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104741"},{"key":"e_1_3_3_105_2","first-page":"100148","article-title":"Brown and beige adipose tissue: new therapeutic targets for metabolic disorders","volume":"10","author":"Magro BS","year":"2024","unstructured":"Magro BS, Dias DPM. Brown and beige adipose tissue: new therapeutic targets for metabolic disorders. Heal Sci Rev. 2024;10:100148.","journal-title":"Heal Sci Rev"},{"key":"e_1_3_3_106_2","article-title":"CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance","volume":"8","author":"Kang HS","year":"2013","unstructured":"Kang HS, Liao G, DeGraff LM, et al. CD44 plays a critical role in regulating diet-induced adipose inflammation, hepatic steatosis, and insulin resistance. PLoS One. 2013;8:e58417.","journal-title":"PLoS One"},{"key":"e_1_3_3_107_2","doi-asserted-by":"publisher","DOI":"10.1186\/s43046-024-00249-9"},{"key":"e_1_3_3_108_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042220-023633"},{"key":"e_1_3_3_109_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-024-01046-7"},{"key":"e_1_3_3_110_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01672"},{"key":"e_1_3_3_111_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-023-09850-0"},{"key":"e_1_3_3_112_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-022-00426-2"},{"key":"e_1_3_3_113_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology11050765"},{"key":"e_1_3_3_114_2","first-page":"667","volume-title":"Advances in Magnetic Resonance Technology and Applications","author":"Sugii S","unstructured":"Sugii S, Velan SS. Chapter 25 - physical and physiological properties of fat. In: Seiberlich N, Gulani V, Calamante F, et al., eds. Advances in Magnetic Resonance Technology and Applications. Academic Press; 2020:667-679."},{"key":"e_1_3_3_115_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-023-03054-1"},{"key":"e_1_3_3_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hnm.2023.200210"},{"key":"e_1_3_3_117_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13339"},{"key":"e_1_3_3_118_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijmr.IJMR_1910_18"},{"key":"e_1_3_3_119_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314982"},{"key":"e_1_3_3_120_2","doi-asserted-by":"publisher","DOI":"10.31083\/FBL24821"},{"key":"e_1_3_3_121_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1354992"},{"key":"e_1_3_3_122_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.800481"},{"key":"e_1_3_3_123_2","doi-asserted-by":"publisher","DOI":"10.3390\/bioengineering12020113"},{"key":"e_1_3_3_124_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202000005"},{"key":"e_1_3_3_125_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.02.015"},{"key":"e_1_3_3_126_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020314"},{"key":"e_1_3_3_127_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.01.021"},{"key":"e_1_3_3_128_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-024-10292-4"},{"key":"e_1_3_3_129_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2022.04.001"},{"key":"e_1_3_3_130_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom11121916"},{"key":"e_1_3_3_131_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-40436-6"},{"key":"e_1_3_3_132_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.006166"},{"key":"e_1_3_3_133_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030552"},{"key":"e_1_3_3_134_2","article-title":"A preclinical platform for assessing antitumor effects and systemic toxicities of cancer drug targets","volume":"119","author":"Li X","year":"2022","unstructured":"Li X, Huang C-H, S\u00e1nchez-Rivera FJ, et al. A preclinical platform for assessing antitumor effects and systemic toxicities of cancer drug targets. Proc Natl Acad Sci USA. 2022;119:e2110557119.","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_3_135_2","doi-asserted-by":"publisher","DOI":"10.1185\/03007997909109412"},{"key":"e_1_3_3_136_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S84849"},{"key":"e_1_3_3_137_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032129"},{"key":"e_1_3_3_138_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.710061"},{"key":"e_1_3_3_139_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2010.02.002"},{"key":"e_1_3_3_140_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsabm.3c00095"},{"key":"e_1_3_3_141_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116623"},{"key":"e_1_3_3_142_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-021-02282-3"},{"key":"e_1_3_3_143_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics2040339"},{"key":"e_1_3_3_144_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252313121"},{"key":"e_1_3_3_145_2","doi-asserted-by":"publisher","DOI":"10.3389\/fddev.2023.1232012"},{"key":"e_1_3_3_146_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20061305"},{"key":"e_1_3_3_147_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25105569"},{"key":"e_1_3_3_148_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.891652"},{"key":"e_1_3_3_149_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01302-1"},{"issue":"1","key":"e_1_3_3_150_2","first-page":"56","article-title":"Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines","volume":"10","author":"Xiao W","year":"2025","unstructured":"Xiao W, Jiang W, Chen Z, et al. Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines. Signal Transduct Target Ther. 2025;10(1):56.","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_3_3_151_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-2272-7_3"},{"key":"e_1_3_3_152_2","first-page":"699","volume-title":"Comprehensive Medicinal Chemistry II","author":"Turner JV","unstructured":"Turner JV, Agatonovic-Kustrin S. 5.29 - In silico prediction of oral bioavailability. In: Taylor JB, Triggle DJ, eds. Comprehensive Medicinal Chemistry II. Elsevier; 2007:699-724."},{"key":"e_1_3_3_153_2","first-page":"3","volume-title":"Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics","author":"Reynolds T","unstructured":"Reynolds T, de Zafra C, Kim A, Gelzleichter TR. Chapter 1 - overview of biopharmaceuticals and comparison with small-molecule drug development. In: Plitnick LM, Herzyk DJ, eds. Nonclinical Development of Novel Biologics, Biosimilars, Vaccines and Specialty Biologics. Academic Press; 2013:3-33."},{"key":"e_1_3_3_154_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10030231"},{"key":"e_1_3_3_155_2","doi-asserted-by":"publisher","DOI":"10.36320\/ajb\/v16.i1.15085"},{"key":"e_1_3_3_156_2","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202400554"},{"key":"e_1_3_3_157_2","first-page":"100061","article-title":"Exploring water\u2212macromolecule interactions at the single-molecule level: a comprehensive review","volume":"3","author":"Shan Y","year":"2024","unstructured":"Shan Y, Bao Y, Cui S. Exploring water\u2212macromolecule interactions at the single-molecule level: a comprehensive review. Supramol Mater. 2024;3:100061.","journal-title":"Supramol Mater"},{"key":"e_1_3_3_158_2","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26313"},{"key":"e_1_3_3_159_2","volume-title":"StatPearls","author":"Bansal AB","year":"2025","unstructured":"Bansal AB, Cassagnol M. HMG-CoA reductase inhibitors. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_160_2","doi-asserted-by":"publisher","DOI":"10.2174\/1871530319666190724114729"},{"key":"e_1_3_3_161_2","volume-title":"StatPearls","author":"Cooper D","year":"2025","unstructured":"Cooper D, Dimri M. Biochemistry, calcium channels. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_162_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70022"},{"key":"e_1_3_3_163_2","volume-title":"StatPearls","author":"Pirahanchi Y","year":"2025","unstructured":"Pirahanchi Y, Dimri M. Biochemistry, Guanylate Cyclase. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_164_2","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20190041"},{"key":"e_1_3_3_165_2","volume-title":"StatPearls","author":"Shahid MA","year":"2025","unstructured":"Shahid MA, Ashraf MA, Sharma S. Physiology, thyroid hormone. In: StatPearls. StatPearls Publishing; 2025."},{"key":"e_1_3_3_166_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1329986"},{"key":"e_1_3_3_167_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-022-01362-9"},{"key":"e_1_3_3_168_2","article-title":"Natural antidiabetic agents: current evidence and development pathways from medicinal plants to clinical use","volume":"20","author":"Uti DE","year":"2025","unstructured":"Uti DE, Atangwho IJ, Alum EU, Egba SI, Ugwu OP-C, Ikechukwu GC. Natural antidiabetic agents: current evidence and development pathways from medicinal plants to clinical use. Nat Prod Commun. 2025;20:1934578X251323393.","journal-title":"Nat Prod Commun"},{"key":"e_1_3_3_169_2","first-page":"1","article-title":"Small molecules in targeted cancer therapy: advances, challenges, and future perspectives","volume":"6","author":"Zhong L","year":"2021","unstructured":"Zhong L, Li Y, Xiong L, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:1-48.","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_3_3_170_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.29926"},{"key":"e_1_3_3_171_2","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13277"},{"key":"e_1_3_3_172_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25153542"},{"key":"e_1_3_3_173_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntm.2024.100054"},{"key":"e_1_3_3_174_2","doi-asserted-by":"publisher","DOI":"10.1186\/s43088-024-00566-x"},{"key":"e_1_3_3_175_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8926"},{"key":"e_1_3_3_176_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118491"},{"key":"e_1_3_3_177_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01826-1"},{"key":"e_1_3_3_178_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2011.08071.x"},{"key":"e_1_3_3_179_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113655"},{"key":"e_1_3_3_180_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.111185"},{"key":"e_1_3_3_181_2","doi-asserted-by":"publisher","DOI":"10.1039\/D4NR04778H"},{"key":"e_1_3_3_182_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00230-3"},{"key":"e_1_3_3_183_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13091332"},{"key":"e_1_3_3_184_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03851-4"},{"key":"e_1_3_3_185_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.08.022"},{"key":"e_1_3_3_186_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c04573"},{"key":"e_1_3_3_187_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2024.101386"},{"key":"e_1_3_3_188_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2024.215754"},{"key":"e_1_3_3_189_2","first-page":"1","article-title":"Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications","volume":"9","author":"Shi Y","year":"2024","unstructured":"Shi Y, Shi M, Wang Y, You J. Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications. Signal Transduct Target Ther. 2024;9:1-43.","journal-title":"Signal Transduct Target Ther"},{"key":"e_1_3_3_190_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics16091114"},{"key":"e_1_3_3_191_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03113-7"},{"key":"e_1_3_3_192_2","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S447496"},{"key":"e_1_3_3_193_2","article-title":"Nanoscale bioconjugates: a review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy","volume":"8","author":"Zhang W","year":"2022","unstructured":"Zhang W, Taheri-Ledari R, Ganjali F, et al. Nanoscale bioconjugates: a review of the structural attributes of drug-loaded nanocarrier conjugates for selective cancer therapy. Heliyon. 2022;8:e09577.","journal-title":"Heliyon"},{"key":"e_1_3_3_194_2","doi-asserted-by":"publisher","DOI":"10.1002\/admi.202200211"},{"key":"e_1_3_3_195_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-025-03433-8"},{"key":"e_1_3_3_196_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1163392"},{"key":"e_1_3_3_197_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202501813"},{"key":"e_1_3_3_198_2","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2024.2436094"},{"key":"e_1_3_3_199_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2025.100218"},{"key":"e_1_3_3_200_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preme.2025.100037"},{"key":"e_1_3_3_201_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.114079"},{"key":"e_1_3_3_202_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14112520"},{"key":"e_1_3_3_203_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103505"},{"key":"e_1_3_3_204_2","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.16535"},{"key":"e_1_3_3_205_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics17050661"},{"key":"e_1_3_3_206_2","doi-asserted-by":"publisher","DOI":"10.3390\/mi13101623"},{"key":"e_1_3_3_207_2","doi-asserted-by":"publisher","DOI":"10.3390\/nano13030574"}],"container-title":["Nutrition and Metabolic Insights"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11786388251408961","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/11786388251408961","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/11786388251408961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:33:07Z","timestamp":1777692787000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/11786388251408961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":206,"alternative-id":["10.1177\/11786388251408961"],"URL":"https:\/\/doi.org\/10.1177\/11786388251408961","relation":{},"ISSN":["1178-6388","1178-6388"],"issn-type":[{"value":"1178-6388","type":"print"},{"value":"1178-6388","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"11786388251408961"}}