{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:01:04Z","timestamp":1790352064251,"version":"4.1.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Fasciola hepatica<\/jats:italic>\n                      is the most common etiologic agent of fasciolosis, a parasitic disease that affects millions of ruminants worldwide and a zoonotic human infection of public health concern. Upon ingestion of infective metacercariae,\n                      <jats:italic>F. hepatica<\/jats:italic>\n                      newly excysted juveniles (FhNEJ) emerge in the duodenum and cross the intestinal wall to initiate a migration route that culminates with their establishment within the hepatic bile ducts. The ability of FhNEJ to exploit the broad-spectrum activities of host plasmin, the central protease of the fibrinolytic system, has been proposed as a strategy employed by these parasites to migrate across the intestinal wall while minimising energy expenditure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mouse intestinal epithelial cells (mPSIEC) were stimulated with FhNEJ and plasminogen (PLG), the zymogen of plasmin, to understand whether FhNEJ-stimulated plasmin generation modulates processes relevant to parasite migration through the intestinal wall, including extracellular matrix (ECM) degradation and the secretion of ECM-degrading enzymes. Plasmin-mediated cellular responses were further examined by proteomic analysis of mPSIEC whole-cell lysates. In parallel, the contribution of the fibrinolytic system in FhNEJ migration was studied in vivo by infecting mice with\n                      <jats:italic>F. hepatica<\/jats:italic>\n                      metacercariae following pharmacological inhibition of fibrinolysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Co-stimulation of mPSIEC with FhNEJ and PLG led to increased plasmin generation in the intestinal pericellular space, which was associated with enhanced collagen degradation and secretion of the urokinase-type plasminogen activator. In addition, using independent cell culture replicates and a stringent statistical pipeline, we identified a robust set of differentially expressed proteins in mPSIEC following stimulation with FhNEJ and PLG. These proteins were involved in cell adhesion, migration, ECM remodelling, immune evasion and fibrinolysis. Despite inter-experimental variability, FhNEJ migration in mice was reduced upon pharmacological inhibition of fibrinolysis, supporting the contribution of host fibrinolysis to parasite invasion in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Altogether, this work provides unprecedented insights into the role of the host fibrinolytic system to FhNEJ migration across mammalian host tissues, thereby advancing our understanding of host\u2013parasite relationships during early stage fasciolosis and highlighting interesting directions for future research in this area.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s13071-025-06992-9","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T15:55:45Z","timestamp":1758729345000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early host\u2013parasite interaction models reveal a key role for fibrinolysis in Fasciola hepatica intestinal migration"],"prefix":"10.1186","volume":"18","author":[{"given":"Judit","family":"Serrat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"L\u00f3pez-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Torres-Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Molina-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"Ruiz-Campillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Siles-Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Gonz\u00e1lez-Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"6992_CR1","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1051\/parasite\/2022034","volume":"29","author":"A Diosdado","year":"2022","unstructured":"Diosdado A, Sim\u00f3n F, Serrat J, Gonz\u00e1lez-Miguel J. Interaction of helminth parasites with the haemostatic system of their vertebrate hosts: a scoping review. Parasite. 2022;29:35.","journal-title":"Parasite"},{"key":"6992_CR2","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.pt.2015.12.012","volume":"32","author":"J Gonz\u00e1lez-Miguel","year":"2016","unstructured":"Gonz\u00e1lez-Miguel J, Siles-Lucas M, Kartashev V, Morch\u00f3n R, Sim\u00f3n F. Plasmin in parasitic chronic infections: friend or foe? Trends Parasitol. 2016;32:325\u201335.","journal-title":"Trends Parasitol"},{"key":"6992_CR3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.actatropica.2013.06.023","volume":"128","author":"L Figuera","year":"2013","unstructured":"Figuera L, G\u00f3mez-Arreaza A, Avil\u00e1n L. Parasitism in optima forma: exploiting the host fibrinolytic system for invasion. Acta Trop. 2013;128:116\u201323.","journal-title":"Acta Trop"},{"key":"6992_CR4","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1111\/j.1365-2141.2005.05444.x","volume":"129","author":"G Cesarman-Maus","year":"2005","unstructured":"Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol. 2005;129:307\u201321.","journal-title":"Br J Haematol"},{"key":"6992_CR5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1055\/s-0037-1616230","volume":"86","author":"HR Lijnen","year":"2001","unstructured":"Lijnen HR. Plasmin and matrix metalloproteinases in vascular remodeling. Thromb Haemost. 2001;86:324\u201333.","journal-title":"Thromb Haemost"},{"key":"6992_CR6","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1189\/jlb.0212056","volume":"92","author":"T Syrovets","year":"2012","unstructured":"Syrovets T, Lunov O, Simmet T. Plasmin as a proinflammatory cell activator. J Leukoc Biol. 2012;92:509\u201319.","journal-title":"J Leukoc Biol"},{"key":"6992_CR7","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/0014-4886(87)90005-7","volume":"95","author":"D Hanta\u00ef","year":"1987","unstructured":"Hanta\u00ef D, Festoff BW. Degradation of muscle basement membrane zone by locally generated plasmin. Exp Neurol. 1987;95:44\u201355.","journal-title":"Exp Neurol"},{"key":"6992_CR8","doi-asserted-by":"publisher","first-page":"3656","DOI":"10.18632\/oncotarget.2849","volume":"6","author":"J-B Oudart","year":"2015","unstructured":"Oudart J-B, Brassart-Pasco S, Vautrin A, Sellier C, Machado C, Dupont-Deshorgue A, et\u00a0al. Plasmin releases the anti-tumor peptide from the NC1 domain of collagen XIX. Oncotarget. 2015;6:3656\u201368.","journal-title":"Oncotarget"},{"key":"6992_CR9","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1055\/s-2007-1003576","volume":"12","author":"RH Goldfarb","year":"1986","unstructured":"Goldfarb RH, Murano G, Brundage R, Siegal GP, Terranova V, Garbisa S, et\u00a0al. Degradation of glycoprotein and collagenous components of the basement membrane: studies with urokinase-type plasminogen activator, alpha-thrombin, and plasmin. Semin Thromb Hemost. 1986;12:335\u20136.","journal-title":"Semin Thromb Hemost"},{"key":"6992_CR10","first-page":"139","volume":"11","author":"M Richardson","year":"1988","unstructured":"Richardson M, Hatton MW, Moore S. The plasma proteases, thrombin and plasmin, degrade the proteoglycan of rabbit aorta segments in vitro: an integrated ultrastructural and biochemical study. Clin Investig Med Med Clin Exp. 1988;11:139\u201350.","journal-title":"Clin Investig Med Med Clin Exp"},{"key":"6992_CR11","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1523\/JNEUROSCI.20-05-02003.2000","volume":"20","author":"Y Nakagami","year":"2000","unstructured":"Nakagami Y, Abe K, Nishiyama N, Matsuki N. Laminin degradation by plasmin regulates long-term potentiation. J Neurosci. 2000;20:2003\u201310.","journal-title":"J Neurosci"},{"key":"6992_CR12","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a005058","author":"P Lu","year":"2011","unstructured":"Lu P, Takai K, Weaver VM, Werb Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol. 2011:a005058. https:\/\/doi.org\/10.1101\/cshperspect.a005058.","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"6992_CR13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.pt.2021.09.008","volume":"38","author":"ZR Pala","year":"2022","unstructured":"Pala ZR, Ernest M, Sweeney B, Jeong YJ, Pascini TV, Alves E Silva TL, et\u00a0al. Beyond cuts and scrapes: plasmin in malaria and other vector-borne diseases. Trends Parasitol. 2022;38:147\u201359.","journal-title":"Trends Parasitol"},{"key":"6992_CR14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010936","volume":"17","author":"J Serrat","year":"2023","unstructured":"Serrat J, Becerro-Recio D, Torres-Valle M, Sim\u00f3n F, Valero MA, Bargues MD, et\u00a0al. Fasciola hepatica juveniles interact with the host fibrinolytic system as a potential early-stage invasion mechanism. PLoS Negl Trop Dis. 2023;17:e0010936.","journal-title":"PLoS Negl Trop Dis"},{"key":"6992_CR15","doi-asserted-by":"publisher","DOI":"10.1186\/s13567-025-01449-4","volume":"56","author":"J Serrat","year":"2025","unstructured":"Serrat J, Torres-Valle M, De Marco Verissimo C, Siles-Lucas M, Gonz\u00e1lez-Miguel J. Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system. Vet Res. 2025;56:20.","journal-title":"Vet Res"},{"key":"6992_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0012069","volume":"18","author":"E O\u2019Kelly","year":"2024","unstructured":"O\u2019Kelly E, Cwiklinski K, De Marco Verissimo C, Calvani NED, L\u00f3pez Corrales J, Jewhurst H, et\u00a0al. Moonlighting on the Fasciola hepatica tegument: enolase, a glycolytic enzyme, interacts with the extracellular matrix and fibrinolytic system of the host. PLoS Negl Trop Dis. 2024;18:e0012069.","journal-title":"PLoS Negl Trop Dis"},{"key":"6992_CR17","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0014-5793(04)00306-0","volume":"563","author":"D Bernal","year":"2004","unstructured":"Bernal D, de la Rubia JE, Carrasco-Abad AM, Toledo R, Mas-Coma S, Marcilla A. Identification of enolase as a plasminogen-binding protein in excretory-secretory products of Fasciola hepatica. FEBS Lett. 2004;563:203\u20136.","journal-title":"FEBS Lett"},{"key":"6992_CR18","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1017\/S0031182018001464","volume":"146","author":"J Gonz\u00e1lez-Miguel","year":"2019","unstructured":"Gonz\u00e1lez-Miguel J, Valero MA, Reguera-Gomez M, Mas-Bargues C, Bargues MD, Sim\u00f3n F, et\u00a0al. Numerous Fasciola plasminogen-binding proteins may underlie blood-brain barrier leakage and explain neurological disorder complexity and heterogeneity in the acute and chronic phases of human fascioliasis. Parasitology. 2019;146:284\u201398.","journal-title":"Parasitology"},{"key":"6992_CR19","first-page":"1","volume-title":"The discovery of Fasciola hepatica and its life cycle","author":"SJ Andrews","year":"2022","unstructured":"Andrews SJ, Cwiklinski K, Dalton JP. The discovery of Fasciola hepatica and its life cycle. 2nd ed. UK: CABI; 2022. p. 1\u201323.","edition":"2"},{"key":"6992_CR20","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.micpath.2017.06.006","volume":"109","author":"K Mehmood","year":"2017","unstructured":"Mehmood K, Zhang H, Sabir AJ, Abbas RZ, Ijaz M, Durrani AZ, et\u00a0al. A review on epidemiology, global prevalence and economical losses of fasciolosis in ruminants. Microb Pathog. 2017;109:253\u201362.","journal-title":"Microb Pathog"},{"key":"6992_CR21","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.vetpar.2013.04.005","volume":"195","author":"JL Fitzpatrick","year":"2013","unstructured":"Fitzpatrick JL. Global food security: the impact of veterinary parasites and parasitologists. Vet Parasitol. 2013;195:233\u201348.","journal-title":"Vet Parasitol"},{"key":"6992_CR22","volume-title":"Global report on neglected tropical diseases 2023","author":"World Health Organization","year":"2023","unstructured":"World Health Organization. Global report on neglected tropical diseases 2023. 1st ed. Geneva: World Health Organization; 2023.","edition":"1"},{"key":"6992_CR23","unstructured":"Pan American Health Organization (PAHO). Operational guidelines for the elimination of human fascioliasis as a public health problem in the Americas. Pan American Health Organization; 2024. https:\/\/iris.paho.org\/handle\/10665.2\/60164"},{"key":"6992_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098165","author":"J Serrat","year":"2023","unstructured":"Serrat J, Torres-Valle M, L\u00f3pez-Garc\u00eda M, Becerro-Recio D, Siles-Lucas M, Gonz\u00e1lez-Miguel J. Molecular characterization of the interplay between Fasciola hepatica juveniles and laminin as a mechanism to adhere to and break through the host intestinal wall. Int J Mol Sci. 2023;24\n:8165. https:\/\/doi.org\/10.3390\/ijms24098165.","journal-title":"Int J Mol Sci"},{"key":"6992_CR25","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.610189","volume":"8","author":"S Pompili","year":"2021","unstructured":"Pompili S, Latella G, Gaudio E, Sferra R, Vetuschi A. The charming world of the extracellular matrix: a dynamic and protective network of the intestinal wall. Front Med. 2021;8:610189.","journal-title":"Front Med"},{"key":"6992_CR26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.pt.2020.09.007","volume":"37","author":"J Gonz\u00e1lez-Miguel","year":"2021","unstructured":"Gonz\u00e1lez-Miguel J, Becerro-Recio D, Siles-Lucas M. Insights into Fasciola hepatica juveniles: crossing the fasciolosis rubicon. Trends Parasitol. 2021;37:35\u201347.","journal-title":"Trends Parasitol"},{"key":"6992_CR27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0010811","volume":"16","author":"D Becerro-Recio","year":"2022","unstructured":"Becerro-Recio D, Serrat J, L\u00f3pez-Garc\u00eda M, Sotillo J, Sim\u00f3n F, Gonz\u00e1lez-Miguel J, et\u00a0al. Proteomics coupled with in vitro model to study the early crosstalk occurring between newly excysted juveniles of Fasciola hepatica and host intestinal cells. PLoS Negl Trop Dis. 2022;16:e0010811.","journal-title":"PLoS Negl Trop Dis"},{"key":"6992_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2020.109028","volume":"278","author":"J Gonz\u00e1lez-Miguel","year":"2020","unstructured":"Gonz\u00e1lez-Miguel J, Becerro-Recio D, Sotillo J, Sim\u00f3n F, Siles-Lucas M. Set up of an in vitro model to study early host\u2013parasite interactions between newly excysted juveniles of Fasciola hepatica and host intestinal cells using a quantitative proteomics approach. Vet Parasitol. 2020;278:109028.","journal-title":"Vet Parasitol"},{"key":"6992_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2025.101005","author":"M L\u00f3pez-Garc\u00eda","year":"2025","unstructured":"L\u00f3pez-Garc\u00eda M, Cwiklinski K, Becerro-Recio D, Ruiz-Campillo MT, Molina-Hern\u00e1ndez V, P\u00e9rez-Ar\u00e9valo J, et\u00a0al. Deciphering the proteomic profile of the parasite Fasciola hepatica after initial vertebrate host infection reveals new insights into its early-stages. Mol Cell Proteomics MCP. 2025;24:101005. https:\/\/doi.org\/10.1016\/j.mcpro.2025.101005.","journal-title":"Mol Cell Proteomics MCP"},{"key":"6992_CR30","doi-asserted-by":"publisher","first-page":"9115","DOI":"10.1073\/pnas.0403210101","volume":"101","author":"KL Reed","year":"2004","unstructured":"Reed KL, Fruin AB, Gower AC, Stucchi AF, Leeman SE, Becker JM. A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity. Proc Natl Acad Sci. 2004;101:9115\u201320.","journal-title":"Proc Natl Acad Sci"},{"key":"6992_CR31","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1021\/acs.jproteome.7b00913","volume":"17","author":"S Moggridge","year":"2018","unstructured":"Moggridge S, Sorensen PH, Morin GB, Hughes CS. Extending the compatibility of the SP3 paramagnetic bead processing approach for proteomics. J Proteome Res. 2018;17:1730\u201340.","journal-title":"J Proteome Res"},{"key":"6992_CR32","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/s41596-018-0082-x","volume":"14","author":"CS Hughes","year":"2019","unstructured":"Hughes CS, Moggridge S, M\u00fcller T, Sorensen PH, Morin GB, Krijgsveld J. Single-pot, solid-phase-enhanced sample preparation for proteomics experiments. Nat Protoc. 2019;14:68\u201385.","journal-title":"Nat Protoc"},{"key":"6992_CR33","doi-asserted-by":"publisher","first-page":"22329","DOI":"10.1038\/s41598-020-77846-w","volume":"10","author":"T Pinheiro","year":"2020","unstructured":"Pinheiro T, Lip KYF, Garc\u00eda-R\u00edos E, Querol A, Teixeira J, van Gulik W, et\u00a0al. Differential proteomic analysis by SWATH-MS unravels the most dominant mechanisms underlying yeast adaptation to non-optimal temperatures under anaerobic conditions. Sci Rep. 2020;10:22329.","journal-title":"Sci Rep"},{"key":"6992_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","volume":"33","author":"J Friedman","year":"2010","unstructured":"Friedman J, Hastie T, Tibshirani R. Regularization paths for generalized linear models via coordinate descent. J Stat Softw. 2010;33:1\u201322.","journal-title":"J Stat Softw"},{"key":"6992_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005752","volume":"13","author":"F Rohart","year":"2017","unstructured":"Rohart F, Gautier B, Singh A, L\u00ea Cao K-A. mixOmics: an R package for \u2019omics feature selection and multiple data integration. PLoS Comput Biol. 2017;13:e1005752.","journal-title":"PLoS Comput Biol"},{"key":"6992_CR36","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et\u00a0al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.","journal-title":"Nucleic Acids Res"},{"key":"6992_CR37","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/s41596-020-00436-7","volume":"16","author":"N Schrode","year":"2021","unstructured":"Schrode N, Seah C, Deans PJM, Hoffman G, Brennand KJ. Analysis framework and experimental design for evaluating synergy-driving gene expression. Nat Protoc. 2021;16:812\u201340.","journal-title":"Nat Protoc"},{"key":"6992_CR38","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41588-019-0497-5","volume":"51","author":"N Schrode","year":"2019","unstructured":"Schrode N, Ho S-M, Yamamuro K, Dobbyn A, Huckins L, Matos MR, et\u00a0al. Synergistic effects of common schizophrenia risk variants. Nat Genet. 2019;51:1475\u201385.","journal-title":"Nat Genet"},{"key":"6992_CR39","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1002\/1878-0261.13622","volume":"18","author":"E Mariella","year":"2024","unstructured":"Mariella E, Grasso G, Miotto M, Buzo K, Reilly NM, Andrei P, et\u00a0al. Transcriptome-wide gene expression outlier analysis pinpoints therapeutic vulnerabilities in colorectal cancer. Mol Oncol. 2024;18:1460\u201385.","journal-title":"Mol Oncol"},{"key":"6992_CR40","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe3362","author":"TL Alves e Silva","year":"2021","unstructured":"Alves e Silva TL, Radtke A, Balaban A, Pascini TV, Pala ZR, Roth A, et\u00a0al. The fibrinolytic system enables the onset of Plasmodium infection in the mosquito vector and the mammalian host. Sci Adv. 2021;7:eabe3362. https:\/\/doi.org\/10.1126\/sciadv.abe3362.","journal-title":"Sci Adv"},{"key":"6992_CR41","first-page":"637","volume":"40","author":"NA Ahad","year":"2011","unstructured":"Ahad NA, Yin TS, Othman AR, Yaacob CR. Sensitivity of normality tests to non-normal data. Sains Malays. 2011;40:637\u201341.","journal-title":"Sains Malays"},{"key":"6992_CR42","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1136\/gut.43.5.656","volume":"43","author":"PR Gibson","year":"1998","unstructured":"Gibson PR, Birchall I, Rosella O, Albert V, Finch CF, Barkla DH, et\u00a0al. Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover. Gut. 1998;43:656\u201363.","journal-title":"Gut"},{"key":"6992_CR43","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3389\/fonc.2018.00024","volume":"8","author":"N Mahmood","year":"2018","unstructured":"Mahmood N, Mihalcioiu C, Rabbani SA. Multifaceted role of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front Oncol. 2018;8:24.","journal-title":"Front Oncol"},{"key":"6992_CR44","doi-asserted-by":"publisher","first-page":"7262","DOI":"10.1016\/S0021-9258(18)34566-6","volume":"257","author":"TC Wun","year":"1982","unstructured":"Wun TC, Ossowski L, Reich E. A proenzyme form of human urokinase. J Biol Chem. 1982;257:7262\u20138.","journal-title":"J Biol Chem"},{"key":"6992_CR45","doi-asserted-by":"publisher","first-page":"41243","DOI":"10.1074\/jbc.M005788200","volume":"275","author":"SL Raza","year":"2000","unstructured":"Raza SL, Nehring LC, Shapiro SD, Cornelius LA. Proteinase-activated receptor-1 regulation of macrophage elastase (MMP-12) secretion by serine proteinases. J Biol Chem. 2000;275:41243\u201350.","journal-title":"J Biol Chem"},{"key":"6992_CR46","first-page":"5997","volume":"50","author":"AR Mackay","year":"1990","unstructured":"Mackay AR, Corbitt RH, Hartzler JL, Thorgeirsson UP. Basement membrane type IV collagen degradation: evidence for the involvement of a proteolytic cascade independent of metalloproteinases. Cancer Res. 1990;50:5997\u20136001.","journal-title":"Cancer Res"},{"key":"6992_CR47","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/s13071-015-0799-0","volume":"8","author":"J Gonz\u00e1lez-Miguel","year":"2015","unstructured":"Gonz\u00e1lez-Miguel J, Morch\u00f3n R, Carret\u00f3n E, Montoya-Alonso JA, Sim\u00f3n F. Can the activation of plasminogen\/plasmin system of the host by metabolic products of Dirofilaria immitis participate in heartworm disease endarteritis? Parasit Vectors. 2015;8:194.","journal-title":"Parasit Vectors"},{"key":"6992_CR48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001012","volume":"5","author":"MW Robinson","year":"2011","unstructured":"Robinson MW, Corvo I, Jones PM, George AM, Padula MP, To J, et\u00a0al. Collagenolytic activities of the major secreted Cathepsin L Peptidases involved in the virulence of the helminth pathogen, Fasciola hepatica. PLoS Negl Trop Dis. 2011;5:e1012.","journal-title":"PLoS Negl Trop Dis"},{"key":"6992_CR49","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.molbiopara.2009.04.005","volume":"167","author":"I Corvo","year":"2009","unstructured":"Corvo I, Cancela M, Cappetta M, Pi-Denis N, Tort JF, Roche L. The major cathepsin L secreted by the invasive juvenile Fasciola hepatica prefers proline in the S2 subsite and can cleave collagen. Mol Biochem Parasitol. 2009;167:41\u20137.","journal-title":"Mol Biochem Parasitol"},{"key":"6992_CR50","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1074\/mcp.RA117.000445","volume":"17","author":"K Cwiklinski","year":"2018","unstructured":"Cwiklinski K, Jewhurst H, McVeigh P, Barbour T, Maule AG, Tort J, et\u00a0al. Infection by the helminth parasite Fasciola hepatica requires rapid regulation of metabolic, virulence, and invasive factors to adjust to its mammalian host. Mol Cell Proteom. 2018;17:792\u2013809.","journal-title":"Mol Cell Proteom"},{"key":"6992_CR51","doi-asserted-by":"publisher","first-page":"10261","DOI":"10.1021\/bi00496a016","volume":"29","author":"K Suzuki","year":"1990","unstructured":"Suzuki K, Enghild JJ, Morodomi T, Salvesen G, Nagase H. Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin). Biochemistry. 1990;29:10261\u201370.","journal-title":"Biochemistry"},{"key":"6992_CR52","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1111\/exd.13522","volume":"27","author":"A Sonoki","year":"2018","unstructured":"Sonoki A, Okano Y, Yoshitake Y. Dermal fibroblasts can activate matrix metalloproteinase-1 independent of keratinocytes via plasmin in a 3D collagen model. Exp Dermatol. 2018;27:520\u20135.","journal-title":"Exp Dermatol"},{"key":"6992_CR53","doi-asserted-by":"publisher","first-page":"2325","DOI":"10.1242\/jcs.02360","volume":"118","author":"WB Saunders","year":"2005","unstructured":"Saunders WB, Bayless KJ, Davis GE. MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. J Cell Sci. 2005;118:2325\u201340.","journal-title":"J Cell Sci"},{"key":"6992_CR54","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S0014-5793(97)00175-0","volume":"405","author":"EN Baramova","year":"1997","unstructured":"Baramova EN, Bajou K, Remacle A, L\u2019Hoir C, Krell HW, Weidle UH, et\u00a0al. Involvement of PA\/plasmin system in the processing of pro-MMP-9 and in the second step of pro-MMP-2 activation. FEBS Lett. 1997;405:157\u201362.","journal-title":"FEBS Lett"},{"key":"6992_CR55","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/ng1297-439","volume":"17","author":"P Carmeliet","year":"1997","unstructured":"Carmeliet P, Moons L, Lijnen R, Baes M, Lema\u00eetre V, Tipping P, et\u00a0al. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet. 1997;17:439\u201344.","journal-title":"Nat Genet"},{"key":"6992_CR56","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1111\/j.1749-6632.1999.tb07696.x","volume":"878","author":"E Hahn-Dantona","year":"1999","unstructured":"Hahn-Dantona E, Ramos-DeSimone N, Sipley J, Nagase H, French DL, Quigley JP. Activation of proMMP-9 by a plasmin\/MMP-3 cascade in a tumor cell model. Regulation by tissue inhibitors of metalloproteinases. Ann N Y Acad Sci. 1999;878:372\u201387.","journal-title":"Ann N Y Acad Sci"},{"key":"6992_CR57","doi-asserted-by":"publisher","first-page":"13066","DOI":"10.1074\/jbc.274.19.13066","volume":"274","author":"N Ramos-DeSimone","year":"1999","unstructured":"Ramos-DeSimone N, Hahn-Dantona E, Sipley J, Nagase H, French DL, Quigley JP. Activation of matrix metalloproteinase-9 (MMP-9) via a converging plasmin\/stromelysin-1 cascade enhances tumor cell invasion. J Biol Chem. 1999;274:13066\u201376.","journal-title":"J Biol Chem"},{"key":"6992_CR58","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1161\/ATVBAHA.109.194589","volume":"29","author":"J Orbe","year":"2009","unstructured":"Orbe J, Rodr\u00edguez JA, Calvayrac O, Rodr\u00edguez-Calvo R, Rodr\u00edguez C, Roncal C, et\u00a0al. Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and increased in patients with enhanced thrombin generation. Arterioscler Thromb Vasc Biol. 2009;29:2109\u201316.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"6992_CR59","doi-asserted-by":"publisher","first-page":"32796","DOI":"10.1038\/srep32796","volume":"6","author":"LS Di Maggio","year":"2016","unstructured":"Di Maggio LS, Tirloni L, Pinto AFM, Diedrich JK, Yates Iii JR, Benavides U, et\u00a0al. Across intra-mammalian stages of the liver fluke Fasciola hepatica: a proteomic study. Sci Rep. 2016;6:32796.","journal-title":"Sci Rep"},{"key":"6992_CR60","doi-asserted-by":"publisher","first-page":"33509","DOI":"10.1074\/jbc.M201941200","volume":"277","author":"L Burysek","year":"2002","unstructured":"Burysek L, Syrovets T, Simmet T. The serine protease plasmin triggers expression of MCP-1 and CD40 in human primary monocytes via activation of p38 MAPK and Janus kinase (JAK)\/STAT signaling pathways. J Biol Chem. 2002;277:33509\u201317.","journal-title":"J Biol Chem"},{"key":"6992_CR61","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1007\/s00109-018-1702-1","volume":"96","author":"T-L Cheng","year":"2018","unstructured":"Cheng T-L, Chen P-K, Huang W-K, Kuo C-H, Cho C-F, Wang K-C, et\u00a0al. Plasminogen\/thrombomodulin signaling enhances VEGF expression to promote cutaneous wound healing. J Mol Med Berl Ger. 2018;96:1333\u201344.","journal-title":"J Mol Med Berl Ger"},{"key":"6992_CR62","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1161\/01.ATV.0000030200.59331.3F","volume":"22","author":"UR Pendurthi","year":"2002","unstructured":"Pendurthi UR, Ngyuen M, Andrade-Gordon P, Petersen LC, Rao LVM. Plasmin induces Cyr61 gene expression in fibroblasts via protease-activated receptor-1 and p44\/42 mitogen-activated protein kinase-dependent signaling pathway. Arterioscler Thromb Vasc Biol. 2002;22:1421\u20136.","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"6992_CR63","doi-asserted-by":"publisher","first-page":"270","DOI":"10.32471\/exp-oncology.2312-8852.vol-42-no-4.15253","volume":"42","author":"AA Tykhomyrov","year":"2020","unstructured":"Tykhomyrov AA, Nedzvetsky VS, A\u011dca CA, Guzyk MM, Korsa VV, Grinenko TV. Plasminogen\/plasmin affects expression of glycolysis regulator TIGAR and induces autophagy in lung adenocarcinoma A549 cells. Exp Oncol. 2020;42:270\u20136.","journal-title":"Exp Oncol"},{"key":"6992_CR64","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12889-021-12383-3","volume":"22","author":"V Ebrahimi","year":"2022","unstructured":"Ebrahimi V, Sharifi M, Mousavi-Roknabadi RS, Sadegh R, Khademian MH, Moghadami M, et\u00a0al. Predictive determinants of overall survival among re-infected COVID-19 patients using the elastic-net regularized Cox proportional hazards model: a machine-learning algorithm. BMC Public Health. 2022;22:10.","journal-title":"BMC Public Health"},{"key":"6992_CR65","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/s41551-023-01034-0","volume":"7","author":"JD Janizek","year":"2023","unstructured":"Janizek JD, Dincer AB, Celik S, Chen H, Chen W, Naxerova K, et\u00a0al. Uncovering expression signatures of synergistic drug responses via ensembles of explainable machine-learning models. Nat Biomed Eng. 2023;7:811\u201329.","journal-title":"Nat Biomed Eng"},{"key":"6992_CR66","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1186\/s12859-019-2994-z","volume":"20","author":"A Torang","year":"2019","unstructured":"Torang A, Gupta P, Klinke DJ 2nd. An elastic-net logistic regression approach to generate classifiers and gene signatures for types of immune cells and T helper cell subsets. BMC Bioinformatics. 2019;20:433.","journal-title":"BMC Bioinformatics"},{"key":"6992_CR67","doi-asserted-by":"publisher","first-page":"13532","DOI":"10.1038\/s41598-023-40780-8","volume":"13","author":"K Zhang","year":"2023","unstructured":"Zhang K, Ye B, Wu L, Ni S, Li Y, Wang Q, et\u00a0al. Machine learning-based prediction of survival prognosis in esophageal squamous cell carcinoma. Sci Rep. 2023;13:13532.","journal-title":"Sci Rep"},{"key":"6992_CR68","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.euprot.2015.02.002","volume":"7","author":"K Kammers","year":"2015","unstructured":"Kammers K, Cole RN, Tiengwe C, Ruczinski I. Detecting significant changes in protein abundance. EuPA Open Proteom. 2015;7:11\u20139.","journal-title":"EuPA Open Proteom"},{"key":"6992_CR69","doi-asserted-by":"publisher","first-page":"20966","DOI":"10.1074\/jbc.M113.484535","volume":"288","author":"H Zhang","year":"2013","unstructured":"Zhang H, Ghai P, Wu H, Wang C, Field J, Zhou G-L. Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion. J Biol Chem. 2013;288:20966\u201377.","journal-title":"J Biol Chem"},{"key":"6992_CR70","doi-asserted-by":"publisher","first-page":"24599","DOI":"10.1074\/jbc.M111.235788","volume":"286","author":"MP Endsley","year":"2011","unstructured":"Endsley MP, Hu Y, Deng Y, He X, Warejcka DJ, Twining SS, et\u00a0al. Maspin, the molecular bridge between the plasminogen activator system and beta1 integrin that facilitates cell adhesion. J Biol Chem. 2011;286:24599\u2013607.","journal-title":"J Biol Chem"},{"key":"6992_CR71","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/S0006-291X(03)01358-5","volume":"308","author":"Y Yamamoto","year":"2003","unstructured":"Yamamoto Y, Nishimura N, Morimoto S, Kitamura H, Manabe S, Kanayama H, et\u00a0al. Distinct roles of Rab3B and Rab13 in the polarized transport of apical, basolateral, and tight junctional membrane proteins to the plasma membrane. Biochem Biophys Res Commun. 2003;308:270\u20135.","journal-title":"Biochem Biophys Res Commun"},{"key":"6992_CR72","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/excr.2000.4855","volume":"257","author":"C Sunshine","year":"2000","unstructured":"Sunshine C, Francis S, Kirk KL. Rab3B regulates ZO-1 targeting and actin organization in PC12 neuroendocrine cells. Exp Cell Res. 2000;257:1\u201310.","journal-title":"Exp Cell Res"},{"key":"6992_CR73","doi-asserted-by":"publisher","first-page":"3324","DOI":"10.1128\/MCB.00144-08","volume":"28","author":"H Nakatsuji","year":"2008","unstructured":"Nakatsuji H, Nishimura N, Yamamura R, Kanayama H-O, Sasaki T. Involvement of actinin-4 in the recruitment of JRAB\/MICAL-L2 to cell-cell junctions and the formation of functional tight junctions. Mol Cell Biol. 2008;28:3324\u201335.","journal-title":"Mol Cell Biol"},{"key":"6992_CR74","doi-asserted-by":"publisher","first-page":"6347","DOI":"10.1038\/onc.2008.218","volume":"27","author":"ER Motrescu","year":"2008","unstructured":"Motrescu ER, Blaise S, Etique N, Messaddeq N, Chenard M-P, Stoll I, et\u00a0al. Matrix metalloproteinase-11\/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions. Oncogene. 2008;27:6347\u201355.","journal-title":"Oncogene"},{"key":"6992_CR75","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13395-016-0089-3","volume":"6","author":"MH Jenkins","year":"2016","unstructured":"Jenkins MH, Alrowaished SS, Goody MF, Crawford BD, Henry CA. Laminin and matrix metalloproteinase 11 regulate fibronectin levels in the zebrafish myotendinous junction. Skelet Muscle. 2016;6:18.","journal-title":"Skelet Muscle"},{"key":"6992_CR76","doi-asserted-by":"publisher","first-page":"eadp0684","DOI":"10.1126\/sciadv.adp0684","volume":"10","author":"NRJ Thielman","year":"2024","unstructured":"Thielman NRJ, Funes V, Davuluri S, Ibanez HE, Sun W-C, Fu J, et\u00a0al. Semaphorin 3D promotes pancreatic ductal adenocarcinoma progression and metastasis through macrophage reprogramming. Sci Adv. 2024;10:eadp0684.","journal-title":"Sci Adv"},{"key":"6992_CR77","first-page":"278","volume-title":"Immunological interaction between Fasciola and its host","author":"S Donnelly","year":"2022","unstructured":"Donnelly S, Flynn R, Mulcahy G, O\u2019Neill S. Immunological interaction between Fasciola and its host. 2nd ed. UK: CABI; 2022. p. 278\u2013308.","edition":"2"},{"key":"6992_CR78","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/mi.2011.37","volume":"4","author":"F-E Johansen","year":"2011","unstructured":"Johansen F-E, Kaetzel CS. Regulation of the polymeric immunoglobulin receptor and IgA transport: new advances in environmental factors that stimulate pIgR expression and its role in mucosal immunity. Mucosal Immunol. 2011;4:598\u2013602.","journal-title":"Mucosal Immunol"},{"key":"6992_CR79","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1136\/gutjnl-2022-328265","volume":"72","author":"T Hendrikx","year":"2023","unstructured":"Hendrikx T, Lang S, Rajcic D, Wang Y, McArdle S, Kim K, et\u00a0al. Hepatic pIgR-mediated secretion of IgA limits bacterial translocation and prevents ethanol-induced liver disease in mice. Gut. 2023;72:1959\u201370.","journal-title":"Gut"},{"key":"6992_CR80","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010226","volume":"18","author":"C De Marco Verissimo","year":"2022","unstructured":"De Marco Verissimo C, Jewhurst HL, Dob\u00f3 J, G\u00e1l P, Dalton JP, Cwiklinski K. Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins. PLoS Pathog. 2022;18:e1010226.","journal-title":"PLoS Pathog"},{"key":"6992_CR81","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1165\/rcmb.2023-0075OC","volume":"70","author":"C Gong","year":"2024","unstructured":"Gong C, Jin Y, Wang X, Mao J, Wang D, Yu X, et\u00a0al. Lack of S1PR2 in macrophage ameliorates sepsis-associated lung injury through inducing IL-33-mediated type 2 immunity. Am J Respir Cell Mol Biol. 2024;70:215\u201325.","journal-title":"Am J Respir Cell Mol Biol"},{"key":"6992_CR82","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.immuni.2022.03.009","volume":"55","author":"M Zhao","year":"2022","unstructured":"Zhao M, Ren K, Xiong X, Xin Y, Zou Y, Maynard JC, et\u00a0al. Epithelial STAT6 O-GlcNAcylation drives a concerted anti-helminth alarmin response dependent on tuft cell hyperplasia and gasdermin C. Immunity. 2022;55:623-638.e5.","journal-title":"Immunity"},{"key":"6992_CR83","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1002\/j.1460-2075.1995.tb07299.x","volume":"14","author":"MB Berkenpas","year":"1995","unstructured":"Berkenpas MB, Lawrence DA, Ginsburg D. Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBO J. 1995;14:2969\u201377.","journal-title":"EMBO J"},{"key":"6992_CR84","first-page":"379","volume-title":"Vaccines for Fasciola: new thinking for an old problem. Fasciolosis","author":"TW Spithill","year":"2022","unstructured":"Spithill TW, Toet H, Rathinasamy V, Zerna G, Swan J, Cameron T, et\u00a0al. Vaccines for Fasciola: new thinking for an old problem. Fasciolosis. 2nd ed. UK: CABI; 2022. p. 379\u2013423.","edition":"2"},{"key":"6992_CR85","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10020155","author":"K Cwiklinski","year":"2022","unstructured":"Cwiklinski K, Drysdale O, L\u00f3pez Corrales J, Corripio-Miyar Y, De Marco VC, Jewhurst H, et\u00a0al. Targeting secreted protease\/anti-protease balance as a vaccine strategy against the helminth Fasciola hepatica. Vaccines. 2022;10:155. https:\/\/doi.org\/10.3390\/vaccines10020155.","journal-title":"Vaccines"}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-06992-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13071-025-06992-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-025-06992-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T20:03:58Z","timestamp":1758744238000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-025-06992-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":85,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["6992"],"URL":"https:\/\/doi.org\/10.1186\/s13071-025-06992-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6822677\/v1","asserted-by":"object"}]},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]},"assertion":[{"value":"4 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 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 animals received humane care in accordance with the guidelines for the protection of animals used for scientific purposes (Directive 2010\/63EU, Decision 2012\/707\/UE, and RD 53\/2013). All procedures were approved by the Ethical Animal Experimentation Committee of the University of C\u00f3rdoba and by the Junta de Andaluc\u00eda (project no. 2021P|\/22).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"387"}}