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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Tuberculosis (TB), caused by the intracellular pathogen Mycobacterium tuberculosis (Mtb), remains a major global health challenge. The prolonged duration of treatment and the emergence of multidrug-resistant strains have highlighted the need for alternative therapeutic strategies. This study investigated the therapeutic potential of Ag85A aptamer-conjugated PEGylated niosomes encapsulating ethanolic extract of propolis (Ag85A-PEGNio\/EEP) using Mtb-infected macrophage model. Ag85A-PEGNio\/EEP exhibited efficient cellular uptake, with more than 99.8% internalization by macrophages, and trafficked host phagolysosome, facilitating targeted delivery of EEP to intracellular Mtb. Ag85A-PEGNio\/EEP treatment showed an anti-mycobacterium efficacy by reducing intracellular Mtb viability by approximately 51.2% compared with untreated controls. Moreover, Ag85A-PEGNio\/EEP modulated macrophage immune responses by significantly increasing the expression of the pro-inflammatory cytokines IL-12 (8.4-fold) and IL-6 (3.8-fold), while markedly decreasing the expression of the anti-inflammatory cytokine IL-10 (6.4-fold). Protein\u2013protein interaction (PPI) network analysis further revealed the association of proteins with immune regulation and antioxidant responses in treated cells. These findings suggest that Ag85A-PEGNio\/EEP functions as a dual-action therapeutic platform by enhancing intracellular anti-mycobacterial activity while balancing host immune responses. This targeted nano-delivery system represents a promising candidate for host-directed TB therapy and further investigations are needed to validate these outcomes and explore their potential applications against TB treatment challenges.<\/jats:p>","DOI":"10.3390\/ijms27167223","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T11:33:46Z","timestamp":1786620826000},"page":"7223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ag85A-PEGylated Propolis Nanoparticles Exhibit Intracellular Antimycobacterial and Host-Protective Activities Against Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Sanonthinee","family":"Sookkree","sequence":"first","affiliation":[{"name":"Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-5505","authenticated-orcid":false,"given":"Sirikwan","family":"Sangboonruang","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Ponrut","family":"Phunpae","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0918-4649","authenticated-orcid":false,"given":"Siriwan","family":"Thaisakun","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narumon","family":"Phaonakrop","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3696-8390","authenticated-orcid":false,"given":"Sittiruk","family":"Roytrakul","sequence":"additional","affiliation":[{"name":"National Center for Genetic Engineering and Biotechnology, National Science and Technology for Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8812-5139","authenticated-orcid":false,"given":"Khajornsak","family":"Tragoolpua","sequence":"additional","affiliation":[{"name":"Division of Clinical Microbiology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Infectious Diseases Research Unit (IDRU), Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). Global Tuberculosis Report 2025, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00036-20","DOI":"10.1128\/CMR.00036-20","article-title":"The echo of pulmonary tuberculosis: Mechanisms of clinical symptoms and other disease-induced systemic complications","volume":"33","author":"Luies","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00281-013-0388-2","article-title":"Macrophages in tuberculosis: Friend or foe","volume":"35","author":"Guirado","year":"2013","journal-title":"Semin. Immunopathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Voskuil, M.I., Bartek, I.L., Visconti, K., and Schoolnik, G.K. (2011). The response of mycobacterium tuberculosis to reactive oxygen and nitrogen species. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00105"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2150449","DOI":"10.1080\/21505594.2022.2150449","article-title":"Pathogenicity and virulence of Mycobacterium tuberculosis","volume":"14","author":"Rahlwes","year":"2023","journal-title":"Virulence"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1440-1843.2010.01738.x","article-title":"Drug-resistant tuberculosis: Past, present, future","volume":"15","author":"Chiang","year":"2010","journal-title":"Respirology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25273","DOI":"10.1074\/jbc.M803899200","article-title":"Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis","volume":"283","author":"Koul","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_8","first-page":"e202553","article-title":"Therapy-induced cardiotoxicity in drug-resistant tuberculosis patients: A systematic review and meta-analysis","volume":"2025","author":"Liastuti","year":"2025","journal-title":"Glob. Cardiol. Sci. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrmicro3200","article-title":"The path of anti-tuberculosis drugs: From blood to lesions to mycobacterial cells","volume":"12","author":"Dartois","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sawicki, R., Widelski, J., Oki\u0144czyc, P., Truszkiewicz, W., Glous, J., and Sieniawska, E. (2022). Exposure to Nepalese propolis alters the metabolic state of Mycobacterium tuberculosis. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.929476"},{"key":"ref_11","first-page":"308249","article-title":"Propolis: A wonder bees product and its pharmacological potentials","volume":"2013","author":"Wagh","year":"2013","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1515\/znc-1999-7-814","article-title":"Synergism between ethanolic extract of propolis (EEP) and anti-tuberculosis drugs on growth of mycobacteria","volume":"54","author":"Scheller","year":"1999","journal-title":"Z. Naturforsch. C J. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Sangboonruang, S., Semakul, N., Suriyaprom, S., Kitidee, K., Khantipongse, J., Intorasoot, S., Tharinjaroen, C.S., Wattananandkul, U., Butr-Indr, B., and Phunpae, P. (2023). Nano-delivery system of ethanolic extract of propolis targeting Mycobacterium tuberculosis via aptamer-modified-niosomes. Nanomaterials, 13.","DOI":"10.3390\/nano13020269"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gky1038","article-title":"PANTHER version 14: More genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools","volume":"47","author":"Mi","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_15","unstructured":"Kesharwani, P. (2020). Chapter 7\u2014Liposomes-and niosomes-based drug delivery systems for tuberculosis treatment. Nanotechnology Based Approaches for Tuberculosis Treatment, Academic Press."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1128\/AAC.48.8.2951-2957.2004","article-title":"Isoniazid pharmacokinetics-pharmacodynamics in an aerosol infection model of tuberculosis","volume":"48","author":"Jayaram","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9368","DOI":"10.1038\/s41467-025-64404-z","article-title":"Fundamental role of spatial positioning of Mycobacterium tuberculosis in mycobacterial survival in macrophages","volume":"16","author":"Sahu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3079","DOI":"10.1016\/j.sjbs.2020.09.016","article-title":"Propolis as a novel antibacterial agent","volume":"27","author":"Almuhayawi","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s11671-018-2457-x","article-title":"Dependence of nanoparticle toxicity on their physical and chemical properties","volume":"13","author":"Sukhanova","year":"2018","journal-title":"Nanoscale Res. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nri3793","article-title":"Cholesterol, inflammation and innate immunity","volume":"15","author":"Tall","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"21763","DOI":"10.1074\/jbc.M501759200","article-title":"Free cholesterol-loaded macrophages are an abundant source of tumor necrosis factor-\u03b1 and interleukin-6: Model of NF-\u03baB- and MAP kinase-dependent inflammation in advanced atherosclerosis","volume":"280","author":"Li","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Alqarni, A.M., Niwasabutra, K., Sahlan, M., Fearnley, H., Fearnley, J., Ferro, V.A., and Watson, D.G. (2019). Propolis exerts an anti-inflammatory effect on PMA-differentiated THP-1 cells via inhibition of purine nucleoside phosphorylase. Metabolites, 9.","DOI":"10.3390\/metabo9040075"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bo, H., Moure, U.A.E., Yang, Y., Pan, J., Li, L., Wang, M., Ke, X., and Cui, H. (2023). Mycobacterium tuberculosis-macrophage interaction: Molecular updates. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1062963"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1165\/rcmb.2010-0319OC","article-title":"IL-10 blocks phagosome maturation in Mycobacterium tuberculosis-infected human macrophages","volume":"45","author":"Keane","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e008303","DOI":"10.1136\/jitc-2023-008303","article-title":"BTN1A1 is a novel immune checkpoint mutually exclusive to PD-L1","volume":"12","author":"Kim","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1038\/s12276-020-00531-5","article-title":"Interleukin-11 signaling underlies fibrosis, parenchymal dysfunction, and chronic inflammation of the airway","volume":"52","author":"Ng","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kapina, M.A., Shepelkova, G.S., Avdeenko, V.G., Guseva, A.N., Kondratieva, T.K., Evstifeev, V.V., and Apt, A.S. (2011). Interleukin-11 drives early lung inflammation during Mycobacterium tuberculosis infection in genetically susceptible mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021878"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.7150\/ijbs.80256","article-title":"Sphingosine-1-phosphate receptor 4 attenuates neutrophilic airway inflammation in experimental asthma via repressing proinflammatory macrophage activation","volume":"19","author":"Wang","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.4049\/jimmunol.1900413","article-title":"TRIM58 restrains intestinal mucosal inflammation by negatively regulating TLR2 in myeloid cells","volume":"203","author":"Eyking","year":"2019","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"RP87935","DOI":"10.7554\/eLife.87935","article-title":"Vangl2 suppresses NF-\u03baB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation","volume":"12","author":"Lu","year":"2024","journal-title":"eLife"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/j.mucimm.2023.05.007","article-title":"Unfolded protein response factor ATF6 augments T helper cell responses and promotes mixed granulocytic airway inflammation","volume":"16","author":"Wu","year":"2023","journal-title":"Mucosal Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, H., Zhang, Q., Wu, W., He, X., Abudukadier, A., Qi, Y., Sun, Q., Li, P., and Xie, J. (2026). A putative Mycobacterium tuberculosis glyoxalase Rv0801 promotes bacterial fitness by alleviating methylglyoxal stress and blunts NRF2-mediated antioxidant defenses. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1745502"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Matsuyama, M., Nonaka, M., Nakajima, M., Morishima, Y., Ishii, Y., and Hizawa, N. (2021). The role of NRF2 in mycobacterial infection. Antioxidants, 10.","DOI":"10.3390\/antiox10121861"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"270","DOI":"10.2119\/molmed.2011.00201","article-title":"Natural killer (NK) cells in antibacterial innate immunity: Angels or devils?","volume":"18","author":"Cavaillon","year":"2012","journal-title":"Mol. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"fty048","DOI":"10.1093\/femspd\/fty048","article-title":"Cyclic nucleotide signaling in Mycobacterium tuberculosis: An expanding repertoire","volume":"76","author":"Johnson","year":"2018","journal-title":"Pathog. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.chom.2015.05.003","article-title":"Mycobacterium tuberculosis differentially activates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1","volume":"17","author":"Wassermann","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/infdis\/jix366","article-title":"An iron-rich diet decreases the mycobacterial burden and correlates with hepcidin upregulation, lower levels of proinflammatory mediators, and increased T-Cell recruitment in a model of Mycobacterium bovis Bacille Calmette-Guerin infection","volume":"216","author":"Agoro","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jtemb.2018.03.007","article-title":"Iron and innate antimicrobial immunity-depriving the pathogen, defending the host","volume":"48","author":"Nairz","year":"2018","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1021\/pr800463v","article-title":"Can proteomics retire the western blot?","volume":"7","author":"Mann","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e1800222","DOI":"10.1002\/pmic.201800222","article-title":"The art of validating quantitative proteomics data","volume":"18","author":"Handler","year":"2018","journal-title":"Proteomics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/s41477-022-01314-8","article-title":"The incongruity of validating quantitative proteomics using western blots","volume":"8","author":"Mehta","year":"2022","journal-title":"Nat. Plants"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","article-title":"UniProt: The Universal Protein Knowledgebase in 2025","volume":"53","author":"Consortium","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00604-017-2550-3","article-title":"Selection of DNA aptamers against Mycobacterium tuberculosis Ag85A, and its application in a graphene oxide-based fluorometric assay","volume":"185","author":"Ansari","year":"2017","journal-title":"Mikrochim. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kietrungruang, K., Sookkree, S., Sangboonruang, S., Semakul, N., Poomanee, W., Kitidee, K., Tragoolpua, Y., and Tragoolpua, K. (2023). Ethanolic extract propolis-loaded niosomes diminish Phospholipase B1, biofilm formation, and intracellular replication of Cryptococcus neoformans in macrophages. Molecules, 28.","DOI":"10.3390\/molecules28176224"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/jac\/dkr472","article-title":"Rapid measurement of antituberculosis drug activity in vitro and in macrophages using bioluminescence","volume":"67","author":"Andreu","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2147\/IDR.S346869","article-title":"The regulation of ManLAM-related gene expression in Mycobacterium tuberculosis with different drug resistance profiles following isoniazid treatment","volume":"15","author":"Yimcharoen","year":"2022","journal-title":"Infect. Drug Resist."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100123","DOI":"10.1016\/j.xpro.2020.100123","article-title":"Dual RNA-sequencing of Mycobacterium tuberculosis-infected cells from a murine infection model","volume":"1","author":"Pisu","year":"2020","journal-title":"STAR Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19029","DOI":"10.1038\/s41598-025-04673-2","article-title":"Exploring intracellular anti-mycobacterium activity of lactoferricin-loaded niosomes: Proteomics insights into Immunomodulation","volume":"15","author":"Sangboonruang","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for mass spectrometry-based shotgun proteomics","volume":"11","author":"Tyanova","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"W398","DOI":"10.1093\/nar\/gkae253","article-title":"MetaboAnalyst 6.0: Towards a unified platform for metabolomics data processing, analysis and interpretation","volume":"52","author":"Pang","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bardou, P., Mariette, J., Escudi\u00e9, F., Djemiel, C., and Klopp, C. (2014). jvenn: An interactive Venn diagram viewer. BMC Bioinform., 15.","DOI":"10.1186\/1471-2105-15-293"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7223\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:56:40Z","timestamp":1788339400000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":53,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167223"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167223","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}