{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:48:05Z","timestamp":1791337685732,"version":"4.3.1"},"reference-count":92,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Project no. GR-2021\u201312374492"],"award-info":[{"award-number":["Project no. GR-2021\u201312374492"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007211","name":"Istituto Nanoscienze, Consiglio Nazionale delle Ricerche","doi-asserted-by":"publisher","award":["Project no. PE00000007"],"award-info":[{"award-number":["Project no. PE00000007"]}],"id":[{"id":"10.13039\/501100007211","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"DOI":"10.1186\/s13287-025-04472-6","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:44:44Z","timestamp":1751359484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein"],"prefix":"10.1186","volume":"16","author":[{"given":"Anna","family":"Pezzotta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bovio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Imberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Corna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Cerullo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gastoldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Benigni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Remuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Morigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3470-1721","authenticated-orcid":false,"given":"Luca","family":"Perico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"4472_CR1","unstructured":"WHO Coronavirus (COVID. -19) Dashboard. https:\/\/covid19.who.int"},{"key":"4472_CR2","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/S1473-3099(20)30243-7","volume":"20","author":"R Verity","year":"2020","unstructured":"Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20:669\u201377.","journal-title":"Lancet Infect Dis"},{"key":"4472_CR3","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","volume":"395","author":"C Huang","year":"2020","unstructured":"Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in wuhan, China. Lancet. 2020;395:497\u2013506.","journal-title":"Lancet"},{"key":"4472_CR4","doi-asserted-by":"publisher","first-page":"e138070","DOI":"10.1172\/jci.insight.138070","volume":"5","author":"S Li","year":"2020","unstructured":"Li S, Jiang L, Li X, Lin F, Wang Y, Li B, et al. Clinical and pathological investigation of patients with severe COVID-19. JCI Insight. 2020;5:e138070.","journal-title":"JCI Insight"},{"key":"4472_CR5","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1038\/s41392-020-00243-2","volume":"5","author":"L Yang","year":"2020","unstructured":"Yang L, Liu S, Liu J, Zhang Z, Wan X, Huang B, et al. COVID-19: Immunopathogenesis and immunotherapeutics. Sig Transduct Target Ther. 2020;5:128.","journal-title":"Sig Transduct Target Ther"},{"key":"4472_CR6","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41392-020-0191-1","volume":"5","author":"M Catanzaro","year":"2020","unstructured":"Catanzaro M, Fagiani F, Racchi M, Corsini E, Govoni S, Lanni C. Immune response in COVID-19: addressing a Pharmacological challenge by targeting pathways triggered by SARS-CoV-2. Sig Transduct Target Ther. 2020;5:84.","journal-title":"Sig Transduct Target Ther"},{"key":"4472_CR7","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1038\/s41418-022-01015-x","volume":"29","author":"Q Li","year":"2022","unstructured":"Li Q, Wang Y, Sun Q, Knopf J, Herrmann M, Lin L, et al. Immune response in COVID-19: what is next? Cell Death Differ. 2022;29:1107\u201322.","journal-title":"Cell Death Differ"},{"key":"4472_CR8","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","volume":"21","author":"A Bonaventura","year":"2021","unstructured":"Bonaventura A, Vecchi\u00e9 A, Dagna L, Martinod K, Dixon DL, Van Tassell BW, et al. Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19. Nat Rev Immunol. 2021;21:319\u201329.","journal-title":"Nat Rev Immunol"},{"key":"4472_CR9","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1038\/s41577-022-00762-9","volume":"22","author":"EM Conway","year":"2022","unstructured":"Conway EM, Mackman N, Warren RQ, Wolberg AS, Mosnier LO, Campbell RA, et al. Understanding COVID-19-associated coagulopathy. Nat Rev Immunol. 2022;22:639\u201349.","journal-title":"Nat Rev Immunol"},{"key":"4472_CR10","first-page":"262","volume":"34","author":"J Zhang","year":"2021","unstructured":"Zhang J, Tecson KM, McCullough PA. Role of endothelial cell receptors in the context of SARS-CoV-2 infection (COVID-19). Proc (Bayl Univ Med Cent). 2021;34:262\u20138.","journal-title":"Proc (Bayl Univ Med Cent)"},{"key":"4472_CR11","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/s41569-021-00665-7","volume":"19","author":"DA Gorog","year":"2022","unstructured":"Gorog DA, Storey RF, Gurbel PA, Tantry US, Berger JS, Chan MY, et al. Current and novel biomarkers of thrombotic risk in COVID-19: a consensus statement from the international COVID-19 thrombosis biomarkers colloquium. Nat Rev Cardiol. 2022;19:475\u201395.","journal-title":"Nat Rev Cardiol"},{"key":"4472_CR12","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41569-020-00469-1","volume":"18","author":"SX Gu","year":"2021","unstructured":"Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, et al. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nat Rev Cardiol. 2021;18:194\u2013209.","journal-title":"Nat Rev Cardiol"},{"key":"4472_CR13","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.tim.2023.06.004","volume":"32","author":"L Perico","year":"2024","unstructured":"Perico L, Benigni A, Remuzzi G. SARS-CoV-2 and the Spike protein in endotheliopathy. Trends Microbiol. 2024;32:53\u201367.","journal-title":"Trends Microbiol"},{"key":"4472_CR14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41392-020-00454-7","volume":"5","author":"Y Jin","year":"2020","unstructured":"Jin Y, Ji W, Yang H, Chen S, Zhang W, Duan G. Endothelial activation and dysfunction in COVID-19: from basic mechanisms to potential therapeutic approaches. Sig Transduct Target Ther. 2020;5:293.","journal-title":"Sig Transduct Target Ther"},{"key":"4472_CR15","doi-asserted-by":"publisher","first-page":"e345","DOI":"10.1016\/S1473-3099(24)00211-1","volume":"24","author":"MJ Peluso","year":"2024","unstructured":"Peluso MJ, Swank ZN, Goldberg SA, Lu S, Dalhuisen T, Borberg E, et al. Plasma-based antigen persistence in the post-acute phase of COVID-19. Lancet Infect Dis. 2024;24:e345\u20137.","journal-title":"Lancet Infect Dis"},{"key":"4472_CR16","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.cmi.2024.09.001","volume":"30","author":"Z Swank","year":"2024","unstructured":"Swank Z, Borberg E, Chen Y, Senussi Y, Chalise S, Manickas-Hill Z, et al. Measurement of Circulating viral antigens post-SARS-CoV-2 infection in a multicohort study. Clin Microbiol Infect. 2024;30:1599\u2013605.","journal-title":"Clin Microbiol Infect"},{"key":"4472_CR17","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1097\/MNH.0000000000000692","volume":"30","author":"L Perico","year":"2021","unstructured":"Perico L, Benigni A, Remuzzi G. Angiotensin-converting enzyme 2: from a vasoactive peptide to the gatekeeper of a global pandemic. Curr Opin Nephrol Hypertens. 2021;30:252\u201363.","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"4472_CR18","doi-asserted-by":"publisher","first-page":"827146","DOI":"10.3389\/fimmu.2022.827146","volume":"13","author":"L Perico","year":"2022","unstructured":"Perico L, Morigi M, Galbusera M, Pezzotta A, Gastoldi S, Imberti B, et al. SARS-CoV-2 Spike protein 1 activates microvascular endothelial cells and complement system leading to platelet aggregation. Front Immunol. 2022;13:827146.","journal-title":"Front Immunol"},{"key":"4472_CR19","doi-asserted-by":"publisher","first-page":"11392","DOI":"10.1038\/s41598-023-38382-5","volume":"13","author":"L Perico","year":"2023","unstructured":"Perico L, Morigi M, Pezzotta A, Locatelli M, Imberti B, Corna D, et al. SARS-CoV-2 Spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a\/C3a receptor signalling. Sci Rep. 2023;13:11392.","journal-title":"Sci Rep"},{"key":"4472_CR20","doi-asserted-by":"publisher","first-page":"eabh2259","DOI":"10.1126\/sciimmunol.abh2259","volume":"6","author":"L Ma","year":"2021","unstructured":"Ma L, Sahu SK, Cano M, Kuppuswamy V, Bajwa J, McPhatter J, et al. Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection. Sci Immunol. 2021;6:eabh2259.","journal-title":"Sci Immunol"},{"key":"4472_CR21","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.kint.2020.05.013","volume":"98","author":"M Noris","year":"2020","unstructured":"Noris M, Benigni A, Remuzzi G. The case of complement activation in COVID-19 multiorgan impact. Kidney Int. 2020;98:314\u201322.","journal-title":"Kidney Int"},{"key":"4472_CR22","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41581-020-00357-4","volume":"17","author":"L Perico","year":"2021","unstructured":"Perico L, Benigni A, Casiraghi F, Ng LFP, Renia L, Remuzzi G. Immunity, endothelial injury and complement-induced coagulopathy in COVID-19. Nat Rev Nephrol. 2021;17:46\u201364.","journal-title":"Nat Rev Nephrol"},{"key":"4472_CR23","doi-asserted-by":"publisher","first-page":"eadg7942","DOI":"10.1126\/science.adg7942","volume":"383","author":"C Cervia-Hasler","year":"2024","unstructured":"Cervia-Hasler C, Br\u00fcningk SC, Hoch T, Fan B, Muzio G, Thompson RC, et al. Persistent complement dysregulation with signs of thromboinflammation in active long Covid. Science. 2024;383:eadg7942.","journal-title":"Science"},{"key":"4472_CR24","doi-asserted-by":"publisher","first-page":"5500","DOI":"10.1016\/j.cell.2024.07.054","volume":"187","author":"MJ Peluso","year":"2024","unstructured":"Peluso MJ, Deeks SG. Mechanisms of long COVID and the path toward therapeutics. Cell. 2024;187:5500\u201329.","journal-title":"Cell"},{"key":"4472_CR25","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12931-024-02795-1","volume":"25","author":"G Gazzaniga","year":"2024","unstructured":"Gazzaniga G, Voltini M, Carletti A, Lenta E, Meloni F, Briganti DF, et al. Potential application of mesenchymal stromal cells as a new therapeutic approach in acute respiratory distress syndrome and pulmonary fibrosis. Respir Res. 2024;25:170.","journal-title":"Respir Res"},{"key":"4472_CR26","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s13287-024-03782-5","volume":"15","author":"M Taherian","year":"2024","unstructured":"Taherian M, Bayati P, Mojtabavi N. Stem cell-based therapy for fibrotic diseases: mechanisms and pathways. Stem Cell Res Ther. 2024;15:170.","journal-title":"Stem Cell Res Ther"},{"key":"4472_CR27","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s12967-024-05358-6","volume":"22","author":"W Lu","year":"2024","unstructured":"Lu W, Yan L, Tang X, Wang X, Du J, Zou Z, et al. Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials. J Transl Med. 2024;22:550.","journal-title":"J Transl Med"},{"key":"4472_CR28","doi-asserted-by":"publisher","first-page":"6402","DOI":"10.1097\/JS9.0000000000001786","volume":"110","author":"C Tang","year":"2024","unstructured":"Tang C, Dziedzic A, Khatib MN, Alhumaid S, Thangavelu L, Parameswari RP, et al. Stem cell therapy for COVID-19 treatment: an umbrella review. Int J Surg. 2024;110:6402\u201317.","journal-title":"Int J Surg"},{"key":"4472_CR29","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1186\/s13287-024-03729-w","volume":"15","author":"A Sitbon","year":"2024","unstructured":"Sitbon A, Hauw-Berlemont C, Mebarki M, Heming N, Mayaux J, Diehl J-L, et al. Treatment of COVID-19-associated ARDS with umbilical cord-derived mesenchymal stromal cells in the STROMA-CoV-2 multicenter randomized double-blind trial: long-term safety, respiratory function, and quality of life. Stem Cell Res Ther. 2024;15:109.","journal-title":"Stem Cell Res Ther"},{"key":"4472_CR30","doi-asserted-by":"publisher","first-page":"103920","DOI":"10.1016\/j.ebiom.2022.103920","volume":"77","author":"R Xu","year":"2022","unstructured":"Xu R, Feng Z, Wang F-S. Mesenchymal stem cell treatment for COVID-19. eBioMedicine. 2022;77:103920.","journal-title":"eBioMedicine"},{"key":"4472_CR31","doi-asserted-by":"publisher","first-page":"2790","DOI":"10.3390\/ijms20112790","volume":"20","author":"C Rota","year":"2019","unstructured":"Rota C, Morigi M, Imberti B. Stem cell therapies in kidney diseases: progress and challenges. Int J Mol Sci. 2019;20:2790.","journal-title":"Int J Mol Sci"},{"key":"4472_CR32","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/978-1-4939-3584-0_5","volume":"1416","author":"M Morigi","year":"2016","unstructured":"Morigi M, Rota C, Remuzzi G. Mesenchymal stem cells in kidney repair. Methods Mol Biol. 2016;1416:89\u2013107.","journal-title":"Methods Mol Biol"},{"key":"4472_CR33","unstructured":"Covid19. mesenchymal stem cells| ClinicalTrials.gov https:\/\/clinicaltrials.gov\/search?cond=Covid19&term=mesenchymal%20stem%20cells"},{"key":"4472_CR34","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41467-017-00937-2","volume":"8","author":"L Perico","year":"2017","unstructured":"Perico L, Morigi M, Rota C, Breno M, Mele C, Noris M, et al. Human mesenchymal stromal cells transplanted into mice stimulate renal tubular cells and enhance mitochondrial function. Nat Commun. 2017;8:983.","journal-title":"Nat Commun"},{"key":"4472_CR35","doi-asserted-by":"publisher","first-page":"e3000411","DOI":"10.1371\/journal.pbio.3000411","volume":"18","author":"NP du Sert","year":"2020","unstructured":"du Sert NP, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, et al. Reporting animal research: explanation and elaboration for the ARRIVE guidelines 2.0. PLOS Biol. 2020;18:e3000411.","journal-title":"PLOS Biol"},{"key":"4472_CR36","doi-asserted-by":"publisher","first-page":"786","DOI":"10.3109\/14653249.2011.563294","volume":"13","author":"C Capelli","year":"2011","unstructured":"Capelli C, Gotti E, Morigi M, Rota C, Weng L, Dazzi F, et al. Minimally manipulated whole human umbilical cord is a rich source of clinical-grade human mesenchymal stromal cells expanded in human platelet lysate. Cytotherapy. 2011;13:786\u2013801.","journal-title":"Cytotherapy"},{"key":"4472_CR37","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1111\/1523-1747.ep12613748","volume":"99","author":"EW Ades","year":"1992","unstructured":"Ades EW, Candal FJ, Swerlick RA, George VG, Summers S, Bosse DC, et al. HMEC-1: establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 1992;99:683\u201390.","journal-title":"J Invest Dermatol"},{"key":"4472_CR38","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1182\/blood.V98.6.1828","volume":"98","author":"M Morigi","year":"2001","unstructured":"Morigi M, Galbusera M, Binda E, Imberti B, Gastoldi S, Remuzzi A, et al. Verotoxin-1-induced up-regulation of adhesive molecules renders microvascular endothelial cells thrombogenic at high shear stress. Blood. 2001;98:1828\u201335.","journal-title":"Blood"},{"key":"4472_CR39","doi-asserted-by":"publisher","first-page":"e0127172","DOI":"10.1371\/journal.pone.0127172","volume":"10","author":"D Macconi","year":"2015","unstructured":"Macconi D, Perico L, Longaretti L, Morigi M, Cassis P, Buelli S, et al. Sirtuin3 dysfunction is the key determinant of skeletal muscle insulin resistance by angiotensin II. PLoS ONE. 2015;10:e0127172.","journal-title":"PLoS ONE"},{"key":"4472_CR40","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.acthis.2017.03.001","volume":"119","author":"AJ Valente","year":"2017","unstructured":"Valente AJ, Maddalena LA, Robb EL, Moradi F, Stuart JA. A simple ImageJ macro tool for analyzing mitochondrial network morphology in mammalian cell culture. Acta Histochem. 2017;119:315\u201326.","journal-title":"Acta Histochem"},{"key":"4472_CR41","doi-asserted-by":"publisher","first-page":"172","DOI":"10.4049\/jimmunol.1100491","volume":"187","author":"M Morigi","year":"2011","unstructured":"Morigi M, Galbusera M, Gastoldi S, Locatelli M, Buelli S, Pezzotta A, et al. Alternative pathway activation of complement by Shiga toxin promotes exuberant C3a formation that triggers microvascular thrombosis. J Immunol. 2011;187:172\u201380.","journal-title":"J Immunol"},{"key":"4472_CR42","doi-asserted-by":"publisher","first-page":"4553","DOI":"10.1182\/blood.V86.12.4553.bloodjournal86124553","volume":"86","author":"M Morigi","year":"1995","unstructured":"Morigi M, Micheletti G, Figliuzzi M, Imberti B, Karmali MA, Remuzzi A, et al. Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions. Blood. 1995;86:4553\u20138.","journal-title":"Blood"},{"key":"4472_CR43","doi-asserted-by":"publisher","first-page":"203941","DOI":"10.1016\/j.cdev.2024.203941","volume":"179","author":"Y Sun","year":"2024","unstructured":"Sun Y, King B, Hamlin AJ, Saniepay M, Gorshkov K, Barker G, et al. Identification of a fibronectin-binding protein signature associated with idiopathic pulmonary fibrosis. Cells Dev. 2024;179:203941.","journal-title":"Cells Dev"},{"key":"4472_CR44","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.bbrc.2019.02.041","volume":"511","author":"E Kawamoto","year":"2019","unstructured":"Kawamoto E, Nago N, Okamoto T, Gaowa A, Masui-Ito A, Sakakura Y, et al. Anti-adhesive effects of human soluble thrombomodulin and its domains. Biochem Biophys Res Commun. 2019;511:312\u20137.","journal-title":"Biochem Biophys Res Commun"},{"key":"4472_CR45","first-page":"11","volume":"16","author":"K Watanabe-Kusunoki","year":"2020","unstructured":"Watanabe-Kusunoki K, Nakazawa D, Ishizu A, Atsumi T. Thrombomodulin as a physiological modulator of intravascular injury. Front Immunol. 2020;16:11.","journal-title":"Front Immunol"},{"key":"4472_CR46","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1161\/ATVBAHA.122.318179","volume":"42","author":"XD Manz","year":"2022","unstructured":"Manz XD, Bogaard HJ, Aman J. Regulation of VWF (Von Willebrand Factor) in inflammatory thrombosis. Arterioscler Thromb Vasc Biol. 2022;42:1307\u201320.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"4472_CR47","doi-asserted-by":"publisher","first-page":"3781","DOI":"10.1002\/j.2040-4603.2022.tb00232.x","volume":"12","author":"CA Foote","year":"2022","unstructured":"Foote CA, Soares RN, Ramirez-Perez FI, Ghiarone T, Aroor A, Manrique-Acevedo C, et al. Endothelial Glycocalyx Compr Physiol. 2022;12:3781\u2013811.","journal-title":"Endothelial Glycocalyx Compr Physiol"},{"key":"4472_CR48","doi-asserted-by":"publisher","first-page":"897087","DOI":"10.3389\/fcvm.2022.897087","volume":"9","author":"A Milusev","year":"2022","unstructured":"Milusev A, Rieben R, Sorvillo N. The endothelial glycocalyx: A possible therapeutic target in cardiovascular disorders. Front Cardiovasc Med. 2022;9:897087.","journal-title":"Front Cardiovasc Med"},{"key":"4472_CR49","doi-asserted-by":"publisher","first-page":"1916","DOI":"10.1002\/ejhf.2326","volume":"23","author":"V Lambadiari","year":"2021","unstructured":"Lambadiari V, Mitrakou A, Kountouri A, Thymis J, Katogiannis K, Korakas E, et al. Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial deformation 4 months after infection. Eur J Heart Fail. 2021;23:1916\u201326.","journal-title":"Eur J Heart Fail"},{"key":"4472_CR50","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.thromres.2016.07.017","volume":"145","author":"M Heurich","year":"2016","unstructured":"Heurich M, Preston RJS, O\u2019Donnell VB, Morgan BP, Collins PW. Thrombomodulin enhances complement regulation through strong affinity interactions with factor H and C3b-Factor H complex. Thromb Res. 2016;145:84\u201392.","journal-title":"Thromb Res"},{"key":"4472_CR51","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.1073\/pnas.1017087108","volume":"108","author":"T Kajander","year":"2011","unstructured":"Kajander T, Lehtinen MJ, Hyv\u00e4rinen S, Bhattacharjee A, Leung E, Isenman DE, et al. Dual interaction of factor H with C3d and glycosaminoglycans in host\u2013nonhost discrimination by complement. Proc Natl Acad Sci U S A. 2011;108:2897\u2013902.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4472_CR52","doi-asserted-by":"publisher","first-page":"877","DOI":"10.3390\/cells12060877","volume":"12","author":"TV Huynh","year":"2023","unstructured":"Huynh TV, Rethi L, Lee T-W, Higa S, Kao Y-H, Chen Y-J. Spike protein impairs mitochondrial function in human cardiomyocytes: mechanisms underlying cardiac injury in COVID-19. Cells. 2023;12:877.","journal-title":"Cells"},{"key":"4472_CR53","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/00207454.2020.1713776","volume":"130","author":"M Bandookwala","year":"2020","unstructured":"Bandookwala M, Sengupta P. 3-Nitrotyrosine: a versatile oxidative stress biomarker for major neurodegenerative diseases. Int J Neurosci. 2020;130:1047\u201362.","journal-title":"Int J Neurosci"},{"key":"4472_CR54","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/cr.2010.178","volume":"21","author":"MJ Morgan","year":"2011","unstructured":"Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-\u03baB signaling. Cell Res. 2011;21:103\u201315.","journal-title":"Cell Res"},{"key":"4472_CR55","doi-asserted-by":"publisher","first-page":"16543","DOI":"10.3390\/ijms242216543","volume":"24","author":"M Locatelli","year":"2023","unstructured":"Locatelli M, Rottoli D, Mahmoud R, Abbate M, Corna D, Cerullo D, et al. Endothelial glycocalyx of peritubular capillaries in experimental diabetic nephropathy: A target of ACE Inhibitor-Induced kidney microvascular protection. Int J Mol Sci. 2023;24:16543.","journal-title":"Int J Mol Sci"},{"key":"4472_CR56","doi-asserted-by":"publisher","first-page":"423","DOI":"10.4081\/916","volume":"48","author":"S Mazzetti","year":"2004","unstructured":"Mazzetti S, Frigerio S, Gelati M, Salmaggi A, Vitellaro-Zuccarello L. Lycopersicon esculentum lectin: an effective and versatile endothelial marker of normal and tumoral blood vessels in the central nervous system. Eur J Histochem. 2004;48:423\u20138.","journal-title":"Eur J Histochem"},{"key":"4472_CR57","doi-asserted-by":"publisher","first-page":"e0135533","DOI":"10.1371\/journal.pone.0135533","volume":"10","author":"AK Scruggs","year":"2015","unstructured":"Scruggs AK, Cioffi EA, Cioffi DL, King JAC, Bauer NN. Lectin-Based characterization of vascular cell microparticle glycocalyx. PLoS ONE. 2015;10:e0135533.","journal-title":"PLoS ONE"},{"key":"4472_CR58","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1161\/CIRCRESAHA.121.318902","volume":"128","author":"Y Lei","year":"2021","unstructured":"Lei Y, Zhang J, Schiavon CR, He M, Chen L, Shen H, et al. SARS-CoV-2 Spike protein impairs endothelial function via downregulation of ACE 2. Circ Res. 2021;128:1323\u20136.","journal-title":"Circ Res"},{"key":"4472_CR59","doi-asserted-by":"publisher","first-page":"166260","DOI":"10.1016\/j.bbadis.2021.166260","volume":"1867","author":"F Li","year":"2021","unstructured":"Li F, Li J, Wang P-H, Yang N, Huang J, Ou J, et al. SARS-CoV-2 Spike promotes inflammation and apoptosis through autophagy by ROS-suppressed PI3K\/AKT\/mTOR signaling. Biochim Biophys Acta Mol Basis Dis. 2021;1867:166260.","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"4472_CR60","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1089\/ars.2018.7703","volume":"31","author":"A Benigni","year":"2019","unstructured":"Benigni A, Cassis P, Conti S, Perico L, Corna D, Cerullo D, et al. Sirt3 deficiency shortens life span and impairs cardiac mitochondrial function rescued by Opa1 gene transfer. Antioxid Redox Signal. 2019;31:1255\u201371.","journal-title":"Antioxid Redox Signal"},{"key":"4472_CR61","doi-asserted-by":"publisher","first-page":"e131849","DOI":"10.1172\/jci.insight.131849","volume":"5","author":"M Morigi","year":"2020","unstructured":"Morigi M, Perico L, Corna D, Locatelli M, Cassis P, Carminati CE, et al. C3a receptor Blockade protects podocytes from injury in diabetic nephropathy. JCI Insight. 2020;5:e131849.","journal-title":"JCI Insight"},{"key":"4472_CR62","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","volume":"7","author":"K Lingappan","year":"2018","unstructured":"Lingappan K. NF-\u03baB in oxidative stress. Curr Opin Toxicol. 2018;7:81\u20136.","journal-title":"Curr Opin Toxicol"},{"key":"4472_CR63","doi-asserted-by":"publisher","first-page":"H317","DOI":"10.1152\/ajpheart.00182.2013","volume":"306","author":"L Xiao","year":"2014","unstructured":"Xiao L, Liu Y, Wang N. New paradigms in inflammatory signaling in vascular endothelial cells. Am J Physiol Heart Circ Physiol. 2014;306:H317\u2013325.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"4472_CR64","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13287-024-04086-4","volume":"16","author":"KN da Silva","year":"2025","unstructured":"da Silva KN, Marim FM, Rocha GV, Costa-Ferro ZSM, Fran\u00e7a LS, de Nonaka A. Functional heterogeneity of mesenchymal stem cells and their therapeutic potential in the K18-hACE2 mouse model of SARS-CoV-2 infection. Stem Cell Res Ther. 2025;16:15.","journal-title":"Stem Cell Res Ther"},{"key":"4472_CR65","doi-asserted-by":"publisher","first-page":"e1012203","DOI":"10.1371\/journal.ppat.1012203","volume":"20","author":"EA Tay","year":"2024","unstructured":"Tay EA, Vijayakumar V, Morales RF, Lee ES, Teo A. Protecting the endothelial glycocalyx in COVID-19. PLOS Pathog. 2024;20:e1012203.","journal-title":"PLOS Pathog"},{"key":"4472_CR66","doi-asserted-by":"publisher","first-page":"e14","DOI":"10.1002\/pgr2.14","volume":"2","author":"V Masola","year":"2024","unstructured":"Masola V, Marrone G, Condoluci C, Franchi M, Stella L, Biolato M, et al. Heparanase-1 and MMPs in Covid-19 and non-Covid-19 pneumonia. Proteoglycan Res. 2024;2:e14.","journal-title":"Proteoglycan Res"},{"key":"4472_CR67","doi-asserted-by":"publisher","first-page":"e00057","DOI":"10.1128\/jvi.00057-22","volume":"96","author":"J Xiang","year":"2022","unstructured":"Xiang J, Lu M, Shi M, Cheng X, Kwakwa KA, Davis JL, et al. Heparanase Blockade as a novel Dual-Targeting therapy for COVID-19. J Virol. 2022;96:e00057\u201322.","journal-title":"J Virol"},{"key":"4472_CR68","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1056\/NEJMoa2021436","volume":"384","author":"P Horby","year":"2021","unstructured":"RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, et al. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384:693\u2013704.","journal-title":"N Engl J Med"},{"key":"4472_CR69","doi-asserted-by":"publisher","first-page":"912726","DOI":"10.1155\/2015\/912726","volume":"2015","author":"N Cui","year":"2015","unstructured":"Cui N, Wang H, Long Y, Su L, Liu D. Dexamethasone suppressed LPS-Induced matrix metalloproteinase and its effect on endothelial glycocalyx shedding. Mediators Inflamm. 2015;2015:912726.","journal-title":"Mediators Inflamm"},{"key":"4472_CR70","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41440-023-01460-2","volume":"47","author":"Q Zhou","year":"2024","unstructured":"Zhou Q, Zhang L, Dong Y, Wang Y, Zhang B, Zhou S, et al. The role of SARS-CoV-2-mediated NF-\u03baB activation in COVID-19 patients. Hypertens Res. 2024;47:375\u201384.","journal-title":"Hypertens Res"},{"key":"4472_CR71","doi-asserted-by":"publisher","first-page":"108255","DOI":"10.1016\/j.intimp.2021.108255","volume":"101","author":"A Attiq","year":"2021","unstructured":"Attiq A, Yao LJ, Afzal S, Khan MA. The triumvirate of NF-\u03baB, inflammation and cytokine storm in COVID-19. Int Immunopharmacol. 2021;101:108255.","journal-title":"Int Immunopharmacol"},{"key":"4472_CR72","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1007\/s00125-011-2110-z","volume":"54","author":"G Rao","year":"2011","unstructured":"Rao G, Ding HG, Huang W, Le D, Maxhimer JB, Oosterhof A, et al. Reactive oxygen species mediate high glucose-induced Heparanase-1 production and Heparan sulphate proteoglycan degradation in human and rat endothelial cells: a potential role in the pathogenesis of atherosclerosis. Diabetologia. 2011;54:1527\u201338.","journal-title":"Diabetologia"},{"key":"4472_CR73","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1681\/ASN.2006020184","volume":"17","author":"A Kramer","year":"2006","unstructured":"Kramer A, van den Hoven M, Rops A, Wijnhoven T, van den Heuvel L, Lensen J, et al. Induction of glomerular heparanase expression in rats with adriamycin nephropathy is regulated by reactive oxygen species and the renin-angiotensin system. J Am Soc Nephrol. 2006;17:2513\u201320.","journal-title":"J Am Soc Nephrol"},{"key":"4472_CR74","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1093\/ndt\/gfp182","volume":"24","author":"MJ van den Hoven","year":"2009","unstructured":"van den Hoven MJ, Waanders F, Rops AL, Kramer AB, van Goor H, Berden JH, et al. Regulation of glomerular heparanase expression by aldosterone, angiotensin II and reactive oxygen species. Nephrol Dial Transpl. 2009;24:2637\u201345.","journal-title":"Nephrol Dial Transpl"},{"key":"4472_CR75","doi-asserted-by":"publisher","first-page":"6685251","DOI":"10.1155\/2023\/6685251","volume":"2023","author":"B Lv","year":"2023","unstructured":"Lv B, Huang S, Huang H, Niu N, Liu J. Endothelial glycocalyx injury in SARS-CoV-2 infection: molecular mechanisms and potential targeted therapy. Mediators Inflamm. 2023;2023:6685251.","journal-title":"Mediators Inflamm"},{"key":"4472_CR76","doi-asserted-by":"publisher","first-page":"339","DOI":"10.3390\/antiox11020339","volume":"11","author":"P Vardakas","year":"2022","unstructured":"Vardakas P, Skaperda Z, Tekos F, Kouretas D. ROS and COVID. Antioxidants. 2022;11:339.","journal-title":"Antioxidants"},{"key":"4472_CR77","doi-asserted-by":"publisher","first-page":"11096","DOI":"10.3390\/ijms222011096","volume":"22","author":"AJ Mayfosh","year":"2021","unstructured":"Mayfosh AJ, Nguyen TK, Hulett MD. The heparanase regulatory network in health and disease. Int J Mol Sci. 2021;22:11096.","journal-title":"Int J Mol Sci"},{"key":"4472_CR78","doi-asserted-by":"publisher","first-page":"e68563","DOI":"10.7554\/eLife.68563","volume":"10","author":"S Khan","year":"2021","unstructured":"Khan S, Shafiei MS, Longoria C, Schoggins JW, Savani RC, Zaki H. SARS-CoV-2 Spike protein induces inflammation via TLR2-dependent activation of the NF-\u03baB pathway. Elife. 2021;10:e68563.","journal-title":"Elife"},{"key":"4472_CR79","doi-asserted-by":"publisher","first-page":"101695","DOI":"10.1016\/j.jbc.2022.101695","volume":"298","author":"JP Robles","year":"2022","unstructured":"Robles JP, Zamora M, Adan-Castro E, Siqueiros-Marquez L, de la Escalera GM, Clapp C. The Spike protein of SARS-CoV-2 induces endothelial inflammation through integrin \u03b15\u03b21 and NF-\u03baB signaling. J Biol Chem. 2022;298:101695.","journal-title":"J Biol Chem"},{"key":"4472_CR80","doi-asserted-by":"publisher","first-page":"103789","DOI":"10.1016\/j.ebiom.2021.103789","volume":"75","author":"L Shi","year":"2022","unstructured":"Shi L, Yuan X, Yao W, Wang S, Zhang C, Zhang B, et al. Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial. eBioMedicine. 2022;75:103789.","journal-title":"eBioMedicine"},{"key":"4472_CR81","doi-asserted-by":"publisher","first-page":"e29757","DOI":"10.1002\/jmv.29757","volume":"96","author":"Y Tang","year":"2024","unstructured":"Tang Y, Zou X, Liu P, Dai Y, Wang S, Su X, et al. Human umbilical cord-derived mesenchymal stem cell transplantation improves the long COVID. J Med Virol. 2024;96:e29757.","journal-title":"J Med Virol"},{"key":"4472_CR82","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/s41573-023-00672-y","volume":"22","author":"G Li","year":"2023","unstructured":"Li G, Hilgenfeld R, Whitley R, De Clercq E. Therapeutic strategies for COVID-19: progress and lessons learned. Nat Rev Drug Discov. 2023;22:449\u201375.","journal-title":"Nat Rev Drug Discov"},{"key":"4472_CR83","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1038\/s41579-024-01036-y","volume":"22","author":"JF-W Chan","year":"2024","unstructured":"Chan JF-W, Yuan S, Chu H, Sridhar S, Yuen K-Y. COVID-19 drug discovery and treatment options. Nat Rev Microbiol. 2024;22:391\u2013407.","journal-title":"Nat Rev Microbiol"},{"key":"4472_CR84","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41581-022-00642-4","volume":"19","author":"N Murakami","year":"2023","unstructured":"Murakami N, Hayden R, Hills T, Al-Samkari H, Casey J, Del Sorbo L, et al. Therapeutic advances in COVID-19. Nat Rev Nephrol. 2023;19:38\u201352.","journal-title":"Nat Rev Nephrol"},{"key":"4472_CR85","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/s41564-023-01356-4","volume":"8","author":"SS Toussi","year":"2023","unstructured":"Toussi SS, Hammond JL, Gerstenberger BS, Anderson AS. Therapeutics for COVID-19. Nat Microbiol. 2023;8:771\u201386.","journal-title":"Nat Microbiol"},{"key":"4472_CR86","doi-asserted-by":"publisher","first-page":"987816","DOI":"10.3389\/fphar.2022.987816","volume":"13","author":"G Remuzzi","year":"2022","unstructured":"Remuzzi G, Schiaffino S, Santoro MG, FitzGerald GA, Melino G, Patrono C. Drugs for the prevention and treatment of COVID-19 and its complications: an update on what we learned in the past 2 years. Front Pharmacol. 2022;13:987816.","journal-title":"Front Pharmacol"},{"key":"4472_CR87","doi-asserted-by":"publisher","first-page":"4545","DOI":"10.1038\/s41467-023-40204-1","volume":"14","author":"E Stadler","year":"2023","unstructured":"Stadler E, Burgess MT, Schlub TE, Khan SR, Chai KL, McQuilten ZK, et al. Monoclonal antibody levels and protection from COVID-19. Nat Commun. 2023;14:4545.","journal-title":"Nat Commun"},{"key":"4472_CR88","doi-asserted-by":"publisher","first-page":"eabq7360","DOI":"10.1126\/scitranslmed.abq7360","volume":"15","author":"E Heilmann","year":"2023","unstructured":"Heilmann E, Costacurta F, Moghadasi SA, Ye C, Pavan M, Bassani D, et al. SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376. Sci Transl Med. 2023;15:eabq7360.","journal-title":"Sci Transl Med"},{"key":"4472_CR89","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1021\/acscentsci.3c00538","volume":"9","author":"Y Hu","year":"2023","unstructured":"Hu Y, Lewandowski EM, Tan H, Zhang X, Morgan RT, Zhang X, et al. Naturally occurring mutations of SARS-CoV-2 main protease confer drug resistance to nirmatrelvir. ACS Cent Sci. 2023;9:1658\u201369.","journal-title":"ACS Cent Sci"},{"key":"4472_CR90","doi-asserted-by":"publisher","first-page":"104559","DOI":"10.1016\/j.ebiom.2023.104559","volume":"91","author":"JD Ip","year":"2023","unstructured":"Ip JD, Chu AW-H, Chan W-M, Leung RC-Y, Abdullah SMU, Sun Y, et al. Global prevalence of SARS-CoV-2 3CL protease mutations associated with nirmatrelvir or ensitrelvir resistance. eBioMedicine. 2023;91:104559.","journal-title":"eBioMedicine"},{"key":"4472_CR91","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/biom14010008","volume":"14","author":"LC Le\u00f3n-Moreno","year":"2023","unstructured":"Le\u00f3n-Moreno LC, Reza-Zald\u00edvar EE, Hern\u00e1ndez-Sapi\u00e9ns MA, Villafa\u00f1a-Estarr\u00f3n E, Garc\u00eda-Martin M, Ojeda-Hern\u00e1ndez DD, et al. Mesenchymal stem Cell-Based therapies in the Post-Acute neurological COVID syndrome: current landscape and opportunities. Biomolecules. 2023;14:8.","journal-title":"Biomolecules"},{"key":"4472_CR92","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1093\/infdis\/jiy478","volume":"219","author":"H Loy","year":"2019","unstructured":"Loy H, Kuok DIT, Hui KPY, Choi MHL, Yuen W, Nicholls JM, et al. Therapeutic implications of human umbilical cord mesenchymal stromal cells in attenuating influenza A(H5N1) Virus\u2013Associated acute lung injury. J Infect Dis. 2019;219:186\u201396.","journal-title":"J Infect Dis"}],"container-title":["Stem Cell Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04472-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13287-025-04472-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13287-025-04472-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:06:06Z","timestamp":1751360766000},"score":1,"resource":{"primary":{"URL":"https:\/\/stemcellres.biomedcentral.com\/articles\/10.1186\/s13287-025-04472-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":92,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4472"],"URL":"https:\/\/doi.org\/10.1186\/s13287-025-04472-6","relation":{},"ISSN":["1757-6512"],"issn-type":[{"value":"1757-6512","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"13 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures involving animals were performed in accordance with institutional guidelines in compliance with national (D.L.n.26, March 4, 2014), and international laws and policies (directive 2010\/63\/EU on the protection of animals used for scientific purposes). This study was approved by the Institutional Animal Care and Use Committees of Istituto di Ricerche Farmacologiche Mario Negri IRCCS and by the Italian Ministry of Health (approval number 581\/2022-PR, issued on 03 October 2022) with the title \u201cValutazione del potenziale terapeutico di inibitori del complemento in un modello murino di COVID-19 indotto da iniezione di proteina Spike di SARS-CoV-2\u201d.Fresh human UC-MSCs were collected from the Obstetrics and Gynecology Unit at Ospedali Riuniti di Bergamo (Bergamo, Italy) after obtaining ethical approval and written informed consent, as previously described [, ].HPMECs were purchased and the vendor declared that cells were isolated from donated human tissues after obtaining permission for their use in in research applications by informed consent or legal authorization.Whole blood specimens from healthy donors were purchased and the vendor declared that all materials were collected with IRB\/IEC\/regulatory approval, using informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"324"}}