{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T05:07:36Z","timestamp":1780636056275,"version":"3.54.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis (TB) treatment is severely hampered by the rise in multi-drug-resistant strains and the prevalence of drug-induced toxicities. Host-Directed Therapies (HDTs) have emerged as a promising strategy to overcome these challenges by modulating innate immunity and circumventing Mycobacterium tuberculosis (Mtb) evasion mechanisms. A hallmark of Mtb pathogenesis is the arrest of phagosome maturation and the induction of host cell necrosis over protective apoptosis. In this study, we investigated the potential HDT effects of \u03b1-Lipoic acid (\u03b1-LA), a well-known antioxidant and metabolic cofactor, within an in vitro model of Mtb-infected THP-1 macrophages. Our findings indicate that \u03b1-LA treatment modulates the macrophage redox state and selectively promotes apoptosis in infected cells without increasing necrotic lysis. Furthermore, \u03b1-LA administration led to a significant, dose-dependent restoration of phagolysosome acidification, effectively reversing the maturation blockade imposed by Mtb. Notably, this enhanced acidification inversely correlated with intracellular bacterial survival. These results suggest that \u03b1-LA might act as a multifaceted HDT agent capable of restoring both host-protective cell death and phagosomal microbicidal mechanisms. Given its established safety profile and its ability to complement standard anti-TB drugs like Bedaquiline (BDQ), \u03b1-LA represents a highly promising candidate for adjunct therapy to improve TB treatment outcomes and mitigate the impact of antibiotic resistance.<\/jats:p>","DOI":"10.3390\/ijms27115053","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"5053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of the Effect of \u03b1-Lipoic Acid in Human Macrophages Infected with Mycobacterium tuberculosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-7265","authenticated-orcid":false,"given":"Alessandro","family":"Salustri","sequence":"first","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2932-2391","authenticated-orcid":false,"given":"Gioia","family":"Cappelletti","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4744-9820","authenticated-orcid":false,"given":"Flavio","family":"De Maio","sequence":"additional","affiliation":[{"name":"Department of Laboratory and Hematologic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy"},{"name":"Microbiota Analysis & Microbial WGS Research Core Facility, GSTeP, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youqing","family":"Shen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Smart Biomaterials, Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filomena","family":"Nuzzi","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-1761","authenticated-orcid":false,"given":"Ivana","family":"Palucci","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory and Hematologic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paglione","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9780-7059","authenticated-orcid":false,"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory and Hematologic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3609-2990","authenticated-orcid":false,"given":"Michela","family":"Sali","sequence":"additional","affiliation":[{"name":"Department of Basic Biotechnological Sciences, Clinical, Intensive and Perioperative, Section of Microbiology, Catholic University of Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy"},{"name":"Department of Laboratory and Hematologic Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Delogu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Universit\u00e0 degli Studi di Parma, Via Gramsci 14, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). Global Tuberculosis Report 2025, World Health Organization."},{"key":"ref_2","first-page":"100295","article-title":"Impacts of MDR\/XDR-TB on the global tuberculosis epidemic: Challenges and opportunities","volume":"7","author":"Chin","year":"2024","journal-title":"Curr. Res. Microb. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liebenberg, D., Gordhan, B.G., and Kana, B.D. (2022). Drug resistant tuberculosis: Implications for transmission, diagnosis, and disease management. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.943545"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1586\/14760584.2016.1170599","article-title":"Why don\u2019t we have an effective tuberculosis vaccine yet?","volume":"15","author":"Davenne","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1016\/j.vaccine.2015.08.033","article-title":"Prospects in Mycobacterium bovis Bacille Calmette et Gu\u00e9rin (BCG) vaccine diversity and delivery: Why does BCG fail to protect against tuberculosis?","volume":"33","author":"Moliva","year":"2015","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Srivastava, S., Dey, S., and Mukhopadhyay, S. (2023). Vaccines against Tuberculosis: Where Are We Now?. Vaccines, 11.","DOI":"10.3390\/vaccines11051013"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.cmi.2023.07.013","article-title":"Recent advances in the treatment of tuberculosis","volume":"30","author":"Motta","year":"2024","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.ccm.2019.07.006","article-title":"Treatment of Drug-Susceptible Tuberculosis","volume":"40","author":"Zha","year":"2019","journal-title":"Clin. Chest Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dobbs, T.E., and Webb, R.M. (2017). Chemotherapy of Tuberculosis. Microbiol. Spectr., 5.","DOI":"10.1128\/microbiolspec.TNMI7-0040-2017"},{"key":"ref_10","first-page":"e62698","article-title":"Treatment and Toxicity Considerations in Tuberculosis: A Narrative Review","volume":"16","author":"Jones","year":"2024","journal-title":"Cureus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.4049\/jimmunol.1201538","article-title":"Abelson Tyrosine Kinase Controls Phagosomal Acidification Required for Killing of Mycobacterium tuberculosis in Human Macrophages","volume":"189","author":"Bruns","year":"2012","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1515\/bmc-2021-0006","article-title":"Everolimus-induced effector mechanism in macrophages and survivability of Erdman, CDC1551 and HN878 strains of Mycobacterium tuberculosis infection","volume":"12","author":"Cao","year":"2021","journal-title":"Biomol. Concepts"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00253-21","DOI":"10.1128\/AAC.00253-21","article-title":"Dual mTORC1\/mTORC2 inhibition as a host-directed therapeutic target in pathologically distinct mouse models of tuberculosis","volume":"65","author":"Tasneen","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1111\/resp.12948","article-title":"Potential effect of ezetimibe against Mycobacterium tuberculosis infection in type II diabetes","volume":"22","author":"Tsai","year":"2017","journal-title":"Respirology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biochi.2015.06.023","article-title":"\u03b1-Lipoic acid attenuates LPS-induced liver injury by improving mitochondrial function in association with GR mitochondrial DNA occupancy","volume":"116","author":"Liu","year":"2015","journal-title":"Biochimie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s43450-023-00370-1","article-title":"Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention","volume":"33","author":"Tripathi","year":"2023","journal-title":"Rev. Bras. Farm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1111\/jocd.12369","article-title":"In Vitro evaluation of chitosan-coated liposome containing both coenzyme Q10 and alpha-lipoic acid: Cytotoxicity, antioxidant activity, and antimicrobial activity","volume":"17","author":"Zhao","year":"2018","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.3164\/jcbn.11-005FR","article-title":"Lipoic acid: Energy metabolism and redox regulation of transcription and cell signaling","volume":"48","author":"Packer","year":"2011","journal-title":"J. Clin. Biochem. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/mnfr.201200608","article-title":"Direct and indirect antioxidant properties of \u03b1-lipoic acid and therapeutic potential","volume":"57","author":"Rochette","year":"2013","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Salehi, B., Berkay Y\u0131lmaz, Y., Antika, G., Boyunegmez Tumer, T., Fawzi Mahomoodally, M., Lobine, D., Akram, M., Riaz, M., Capanoglu, E., and Sharopov, F. (2019). Insights on the use of \u03b1-lipoic acid for therapeutic purposes. Biomolecules, 9.","DOI":"10.3390\/biom9080356"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1529\/biophysj.106.099366","article-title":"Cholesterol level regulates endosome motility via rab proteins","volume":"94","author":"Chen","year":"2008","journal-title":"Biophys. J."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"101852","DOI":"10.1016\/j.mito.2024.101852","article-title":"Host and microbial regulation of mitochondrial reactive oxygen species during mycobacterial infections","volume":"75","author":"Kim","year":"2024","journal-title":"Mitochondrion"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/15216549700204191","article-title":"The role of reactive oxygen species (ROS) in the effector mechanisms of human antimycobacterial immunity","volume":"43","author":"Fazal","year":"1997","journal-title":"IUBMB Life"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Yang, S., Ouyang, J., Lu, Y., Harypursat, V., and Chen, Y. (2022). A Dual Role of Heme Oxygenase-1 in Tuberculosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.842858"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/biof.5520060303","article-title":"Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization","volume":"6","author":"Han","year":"1997","journal-title":"BioFactors"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1007\/s11274-023-03735-9","article-title":"Mycobacterium tuberculosis and its clever approaches to escape the deadly macrophage","volume":"39","author":"Krishnan","year":"2023","journal-title":"World J. Microbiol. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ghoshal, A., Verma, A., Bhaskar, A., and Dwivedi, V.P. (2024). The uncharted territory of host-pathogen interaction in tuberculosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1339467"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bao, C., Zhang, Y., Feng, J., Hong, X., Gao, N., and Feng, G. (2025). Deciphering tuberculosis: Lysosome-centric insights into pathogenesis and therapies. Front. Cell. Infect. Microbiol., 15.","DOI":"10.3389\/fcimb.2025.1582037"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1016\/j.micinf.2012.07.001","article-title":"Mycobacterium tuberculosis modulators of the macrophage\u2019s cellular events","volume":"14","author":"Poirier","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1034\/j.1600-0854.2003.00120.x","article-title":"Mycobacterium tuberculosis phagosome maturation arrest: Selective targeting of Pl3P-dependent membrane trafficking","volume":"4","author":"Vergne","year":"2003","journal-title":"Traffic"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/mi.2011.3","article-title":"Apoptosis is an innate defense function of macrophages against Mycobacterium tuberculosis","volume":"4","author":"Behar","year":"2011","journal-title":"Mucosal Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3349\/ymj.2009.50.1.1","article-title":"Macrophage apoptosis in tuberculosis","volume":"50","author":"Lee","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Butler, R.E., Brodin, P., Jang, J., Jang, M.-S., Robertson, B.D., Gicquel, B., and Stewart, G.R. (2012). The Balance of Apoptotic and Necrotic Cell Death in Mycobacterium tuberculosis Infected Macrophages Is Not Dependent on Bacterial Virulence. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047573"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/ni.1758","article-title":"Mycobacterium tuberculosis evades macrophage defenses by inhibiting plasma membrane repair","volume":"10","author":"Divangahi","year":"2009","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Salustri, A., De Maio, F., Palmieri, V., Santarelli, G., Palucci, I., Bianco, D.M., Marchionni, F., Bellesi, S., Ciasca, G., and Perini, G. (2023). Evaluation of the Toxic Activity of the Graphene Oxide in the Ex Vivo Model of Human PBMC Infection with Mycobacterium tuberculosis. Microorganisms, 11.","DOI":"10.3390\/microorganisms11030554"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"112721","DOI":"10.1016\/j.jim.2019.112721","article-title":"Standardized protocols for differentiation of THP-1 cells to macrophages with distinct M(IFN\u03b3+LPS), M(IL-4) and M(IL-10) phenotypes","volume":"478","author":"Baxter","year":"2020","journal-title":"J. Immunol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"288.e1","DOI":"10.1016\/j.cmi.2020.10.019","article-title":"Multicentre testing of the EUCAST broth microdilution reference method for MIC determination on Mycobacterium tuberculosis","volume":"27","author":"Werngren","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102522","DOI":"10.1016\/j.tube.2024.102522","article-title":"Exploring diagnostic methods for drug-resistant tuberculosis: A comprehensive overview","volume":"148","author":"Sanchini","year":"2024","journal-title":"Tuberculosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.1128\/JCM.01123-16","article-title":"A multilaboratory, multicountry study to determine bedaquiline MIC quality control ranges for phenotypic drug susceptibility testing","volume":"54","author":"Kaniga","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1590\/S1517-83822013000100042","article-title":"Measuring of Mycobacterium Tuberculosis Growth. A Correlation of the Optical Measurements with Colony Forming Units","volume":"44","year":"2013","journal-title":"Braz. J. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Santarelli, G., Perini, G., Salustri, A., Palucci, I., Rosato, R., Palmieri, V., Iacovelli, C., Bellesi, S., Sali, M., and Sanguinetti, M. (2024). Unraveling the potential of graphene quantum dots against Mycobacterium tuberculosis infection. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1395815"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s44280-024-00065-9","article-title":"Phagocytosis: Strategies for macrophages to hunt Mycobacterium tuberculosis","volume":"2","author":"Liu","year":"2024","journal-title":"One Health Adv."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"100300","DOI":"10.1016\/j.jctube.2022.100300","article-title":"Tuberculosis pathophysiology and anti-VEGF intervention","volume":"27","author":"Maison","year":"2022","journal-title":"J. Clin. Tuberc. Other Mycobact. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"110715","DOI":"10.1016\/j.cellsig.2023.110715","article-title":"The dynamics of Mycobacterium tuberculosis phagosome and the fate of infection","volume":"108","author":"Zhang","year":"2023","journal-title":"Cell. Signal."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"De Maio, F., Palmieri, V., Santarelli, G., Perini, G., Salustri, A., Palucci, I., Sali, M., Gervasoni, J., Primiano, A., and Ciasca, G. (2020). Graphene Oxide-Linezolid Combination as Potential New Anti-Tuberculosis Treatment. Nanomaterials, 10.","DOI":"10.3390\/nano10081431"},{"key":"ref_47","first-page":"465","article-title":"Analysis of cell viability by the lactate dehydrogenase assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1128\/IAI.71.1.254-259.2003","article-title":"THP-1 cell apoptosis in response to Mycobacterial infection","volume":"71","author":"Riendeau","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3892\/etm.2014.2111","article-title":"Amplificarecombinant cpn 0810 stimulates proinflammatory cytokine expression and apoptosis in human monocytes","volume":"9","author":"Chen","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1007\/s10895-018-2306-4","article-title":"The Detailed Comparison of Cell Death Detected by Annexin V-PI Counterstain Using Fluorescence Microscope, Flow Cytometry and Automated Cell Counter in Mammalian and Microalgae Cells","volume":"28","author":"Uzuner","year":"2018","journal-title":"J. Fluoresc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T04:54:40Z","timestamp":1780635280000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/11\/5053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":50,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27115053"],"URL":"https:\/\/doi.org\/10.3390\/ijms27115053","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]}}}