{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:02:14Z","timestamp":1790074934670,"version":"4.0.1"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]},{"name":"This work was supported by a grant from the European Regional Development Fund","award":["Grant Agreement KK.01.1.1.04.0086"],"award-info":[{"award-number":["Grant Agreement KK.01.1.1.04.0086"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Babesiosis is a disease of significant medically and veterinary importance with worldwide distribution. It is caused by intra-erythrocyte protozoal parasites, with\n                    <jats:italic>Babesia rossi<\/jats:italic>\n                    causing the most severe clinical signs of all the large\n                    <jats:italic>Babesia<\/jats:italic>\n                    parasites infecting dogs. The disease can be clinically classified into uncomplicated and complicated forms with a wide range of clinical presentations from a mild, subclinical illness to complicated forms and death. The aim of this study was to assess serum proteomic profiles from dogs with babesiosis and healthy dogs using a label-based proteomics approach. Altogether 32 dogs naturally infected with\n                    <jats:italic>B. rossi<\/jats:italic>\n                    (subdivided into 18 uncomplicated cases and 14 complicated cases of babesiosis) and 20 healthy dogs were included. There were 78 proteins with significantly different abundances between the three groups of dogs. Elucidation of proteins and pathways involved in canine babesiosis caused by\n                    <jats:italic>B. rossi<\/jats:italic>\n                    have revealed key differences associated with haemostasis, innate immune system, lipid metabolism and inflammation. Shotgun proteomic profiling allowed identification of potential serum biomarkers for differentiation of disease severity in canine babesiosis caused by\n                    <jats:italic>B. rossi<\/jats:italic>\n                    . These findings may be applicable to the study of host-parasite interactions and the development of novel therapeutic targets.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-37312-9","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T17:05:11Z","timestamp":1687539911000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Serum proteome profiling of naturally acquired Babesia rossi infection in dogs"],"prefix":"10.1038","volume":"13","author":[{"given":"Josipa","family":"Kule\u0161","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Rubi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Farka\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Bari\u0107 Rafaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Goti\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Crnogaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Burchmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Eckersall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Mrljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Leisewitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"37312_CR1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1017\/S0031182097001686","volume":"115","author":"T Schetters","year":"2007","unstructured":"Schetters, T., Kleuskens, J., Scholtes, N., Moubri, K. & Gorenflot, A. Different Babesia canis isolates, different diseases. Parasitology 115, 485\u2013493 (2007).","journal-title":"Parasitology"},{"key":"37312_CR2","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/1756-3305-2-s1-s4","volume":"2","author":"PJ Irwin","year":"2009","unstructured":"Irwin, P. J. Canine babesiosis: From molecular taxonomy to control. Parasit. Vectors 2, S4. https:\/\/doi.org\/10.1186\/1756-3305-2-s1-s4 (2009).","journal-title":"Parasit. Vectors"},{"key":"37312_CR3","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.vetpar.2006.01.035","volume":"138","author":"G Uilenberg","year":"2006","unstructured":"Uilenberg, G. Babesia\u2013a historical overview. Vet. Parasitol. 138, 3\u201310. https:\/\/doi.org\/10.1016\/j.vetpar.2006.01.035 (2006).","journal-title":"Vet. Parasitol."},{"key":"37312_CR4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1051\/vetres\/2009020","volume":"40","author":"A Chauvin","year":"2009","unstructured":"Chauvin, A., Moreau, E., Bonnet, S., Plantard, O. & Malandrin, L. Babesia and its hosts: Adaptation to long-lasting interactions as a way to achieve efficient transmission. Vet. Res. 40, 37. https:\/\/doi.org\/10.1051\/vetres\/2009020 (2009).","journal-title":"Vet. Res."},{"key":"37312_CR5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.vetpar.2019.06.005","volume":"271","author":"AL Leisewitz","year":"2019","unstructured":"Leisewitz, A. L. et al. A clinical and pathological description of 320 cases of naturally acquired Babesia rossi infection in dogs. Vet. Parasitol. 271, 22\u201330. https:\/\/doi.org\/10.1016\/j.vetpar.2019.06.005 (2019).","journal-title":"Vet. Parasitol."},{"key":"37312_CR6","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.vetpar.2006.01.047","volume":"138","author":"LS Jacobson","year":"2006","unstructured":"Jacobson, L. S. The South African form of severe and complicated canine babesiosis: Clinical advances 1994\u20132004. Vet. Parasitol. 138, 126\u2013139. https:\/\/doi.org\/10.1016\/j.vetpar.2006.01.047 (2006).","journal-title":"Vet. Parasitol."},{"key":"37312_CR7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.pt.2011.11.003","volume":"28","author":"V Matijatko","year":"2012","unstructured":"Matijatko, V., Torti, M. & Schetters, T. P. Canine babesiosis in Europe: How many diseases?. Trends Parasitol. 28, 99\u2013105. https:\/\/doi.org\/10.1016\/j.pt.2011.11.003 (2012).","journal-title":"Trends Parasitol."},{"key":"37312_CR8","doi-asserted-by":"publisher","first-page":"158","DOI":"10.4102\/jsava.v72i3.640","volume":"72","author":"C Welzl","year":"2001","unstructured":"Welzl, C., Leisewitz, A. L., Jacobson, L. S., Vaughan-Scott, T. & Myburgh, E. Systemic inflammatory response syndrome and multiple-organ damage\/dysfunction in complicated canine babesiosis. J. S. Afr. Vet. Assoc. 72, 158\u2013162. https:\/\/doi.org\/10.4102\/jsava.v72i3.640 (2001).","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"37312_CR9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.4102\/ojvr.v76i1.66","volume":"76","author":"JP Schoeman","year":"2009","unstructured":"Schoeman, J. P. Canine babesiosis: Tick-borne diseases. Onderstepoort J. Vet. Res. 76, 59\u201366 (2009).","journal-title":"Onderstepoort J. Vet. Res."},{"key":"37312_CR10","first-page":"119","volume":"6","author":"LS Koster","year":"2015","unstructured":"Koster, L. S., Lobetti, R. G. & Kelly, P. Canine babesiosis: A perspective on clinical complications, biomarkers, and treatment. Vet. Med. Res. Rep. 6, 119\u2013128 (2015).","journal-title":"Vet. Med. Res. Rep."},{"key":"37312_CR11","first-page":"134","volume":"65","author":"LS Jacobson","year":"1994","unstructured":"Jacobson, L. S. & Clark, I. A. The pathophysiology of canine babesiosis: New approaches to an old puzzle. J. S. Afr. Vet. Assoc. 65, 134\u2013145 (1994).","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"37312_CR12","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4102\/jsava.v72i1.604","volume":"72","author":"RG Lobetti","year":"2001","unstructured":"Lobetti, R. G. & Jacobson, L. S. Renal involvement in dogs with babesiosis. J. S. Afr. Vet. Assoc. 72, 23\u201328 (2001).","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"37312_CR13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1080\/00034983.1998.11813308","volume":"92","author":"F Reyers","year":"1998","unstructured":"Reyers, F. et al. Canine babesiosis in South Africa: More than one disease. Does this serve as a model for falciparum malaria?. Ann. Trop. Med. Parasitol. 92, 503\u2013511 (1998).","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"37312_CR14","doi-asserted-by":"publisher","first-page":"e0150113","DOI":"10.1371\/journal.pone.0150113","volume":"11","author":"A Goddard","year":"2016","unstructured":"Goddard, A., Leisewitz, A. L., Kjelgaard-Hansen, M., Kristensen, A. T. & Schoeman, J. P. Excessive pro-inflammatory serum cytokine concentrations in virulent canine babesiosis. PLoS ONE 11, e0150113. https:\/\/doi.org\/10.1371\/journal.pone.0150113 (2016).","journal-title":"PLoS ONE"},{"key":"37312_CR15","doi-asserted-by":"publisher","DOI":"10.4102\/jsava.v71i3.710","author":"MG Collett","year":"2000","unstructured":"Collett, M. G. Survey of canine babesiosis in South Africa. J. S. Afr. Vet. Assoc. https:\/\/doi.org\/10.4102\/jsava.v71i3.710 (2000).","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"37312_CR16","first-page":"27","volume":"35","author":"H Botha","year":"1964","unstructured":"Botha, H. The cerebral form of babesiosis in dogs. J. S. Afr. Vet. Assoc. 35, 27\u201328 (1964).","journal-title":"J. S. Afr. Vet. Assoc."},{"key":"37312_CR17","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/nrmicro2420","volume":"8","author":"DE Goldberg","year":"2010","unstructured":"Goldberg, D. E. & Cowman, A. F. Moving in and renovating: exporting proteins from Plasmodium into host erythrocytes. Nat. Rev. Microbiol. 8, 617\u2013621. https:\/\/doi.org\/10.1038\/nrmicro2420 (2010).","journal-title":"Nat. Rev. Microbiol."},{"key":"37312_CR18","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1111\/j.1365-2958.2007.05850.x","volume":"65","author":"CL Hutchings","year":"2007","unstructured":"Hutchings, C. L. et al. New insights into the altered adhesive and mechanical properties of red blood cells parasitized by Babesia bovis. Mol. Microbiol. 65, 1092\u20131105. https:\/\/doi.org\/10.1111\/j.1365-2958.2007.05850.x (2007).","journal-title":"Mol. Microbiol."},{"key":"37312_CR19","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1097\/MOH.0b013e328352245a","volume":"19","author":"CA Lobo","year":"2012","unstructured":"Lobo, C. A., Rodriguez, M. & Cursino-Santos, J. R. Babesia and red cell invasion. Curr. Opin. Hematol. 19, 170\u2013175. https:\/\/doi.org\/10.1097\/MOH.0b013e328352245a (2012).","journal-title":"Curr. Opin. Hematol."},{"key":"37312_CR20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/1746-6148-10-111","volume":"10","author":"J Kule\u0161","year":"2014","unstructured":"Kule\u0161, J. et al. Identification of serum biomarkers in dogs naturally infected with Babesia canis canis using a proteomic approach. BMC Vet. Res. 10, 111. https:\/\/doi.org\/10.1186\/1746-6148-10-111 (2014).","journal-title":"BMC Vet. Res."},{"key":"37312_CR21","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.rvsc.2016.02.011","volume":"105","author":"J Kule\u0161","year":"2016","unstructured":"Kule\u0161, J. et al. Plasma biomarkers of SIRS and MODS associated with canine babesiosis. Res. Vet. Sci. 105, 222\u2013228. https:\/\/doi.org\/10.1016\/j.rvsc.2016.02.011 (2016).","journal-title":"Res. Vet. Sci."},{"key":"37312_CR22","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1111\/jvim.12016","volume":"27","author":"C Liebenberg","year":"2013","unstructured":"Liebenberg, C. et al. Hemostatic abnormalities in uncomplicated babesiosis (Babesia rossi) in dogs. J. Vet. Intern. Med. 27, 150\u2013156. https:\/\/doi.org\/10.1111\/jvim.12016 (2013).","journal-title":"J. Vet. Intern. Med."},{"key":"37312_CR23","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1016\/j.tvjl.2015.05.008","volume":"205","author":"A Goddard","year":"2015","unstructured":"Goddard, A., Leisewitz, A. L., Kristensen, A. T. & Schoeman, J. P. Platelet activation and platelet-leukocyte interaction in dogs naturally infected with Babesia rossi. Vet. J. 205, 387\u2013392. https:\/\/doi.org\/10.1016\/j.tvjl.2015.05.008 (2015).","journal-title":"Vet. J."},{"key":"37312_CR24","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.tvjl.2012.09.009","volume":"196","author":"A Goddard","year":"2013","unstructured":"Goddard, A., Wiinberg, B., Schoeman, J. P., Kristensen, A. T. & Kjelgaard-Hansen, M. Mortality in virulent canine babesiosis is associated with a consumptive coagulopathy. Vet. J. 196, 213\u2013217. https:\/\/doi.org\/10.1016\/j.tvjl.2012.09.009 (2013).","journal-title":"Vet. J."},{"key":"37312_CR25","doi-asserted-by":"publisher","first-page":"49","DOI":"10.11613\/BM.2012.006","volume":"22","author":"S Margetic","year":"2012","unstructured":"Margetic, S. Inflammation and haemostasis. Biochem. Med. 22, 49\u201362 (2012).","journal-title":"Biochem. Med."},{"key":"37312_CR26","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1111\/vcp.12306","volume":"44","author":"A Goddard","year":"2015","unstructured":"Goddard, A., Leisewitz, A. L., Kristensen, A. T. & Schoeman, J. P. Platelet indices in dogs with Babesia rossi infection. Vet. Clin. Pathol. 44, 493\u2013497. https:\/\/doi.org\/10.1111\/vcp.12306 (2015).","journal-title":"Vet. Clin. Pathol."},{"key":"37312_CR27","first-page":"259","volume":"80","author":"Z Zvorc","year":"2010","unstructured":"Zvorc, Z., Rafaj, R. B., Kules, J. & Mrljak, V. Erythrocyte and platelet indices in babesiosis of dogs\/Promjene u broju eritrocita i trombocita pokazatelji su babezioze u pasa. Vet. Arh. 80, 259 (2010).","journal-title":"Vet. Arh."},{"key":"37312_CR28","doi-asserted-by":"publisher","first-page":"e12630","DOI":"10.1111\/pim.12630","volume":"41","author":"A Leisewitz","year":"2019","unstructured":"Leisewitz, A. et al. Disease severity and blood cytokine concentrations in dogs with natural Babesia rossi infection. Parasite Immunol. 41, e12630. https:\/\/doi.org\/10.1111\/pim.12630 (2019).","journal-title":"Parasite Immunol."},{"key":"37312_CR29","doi-asserted-by":"publisher","first-page":"e12706","DOI":"10.1111\/pim.12706","volume":"42","author":"A Henning","year":"2020","unstructured":"Henning, A., Clift, S. J. & Leisewitz, A. L. The pathology of the spleen in lethal canine babesiosis caused by Babesia rossi. Parasite Immunol. 42, e12706. https:\/\/doi.org\/10.1111\/pim.12706 (2020).","journal-title":"Parasite Immunol."},{"key":"37312_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00257","author":"NS Merle","year":"2015","unstructured":"Merle, N. S., Noe, R., Halbwachs-Mecarelli, L., Fremeaux-Bacchi, V. & Roumenina, L. T. Complement system part II: Role in immunity. Front. Immunol. https:\/\/doi.org\/10.3389\/fimmu.2015.00257 (2015).","journal-title":"Front. Immunol."},{"key":"37312_CR31","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/jvim.14871","volume":"32","author":"DM Hernandez","year":"2018","unstructured":"Hernandez, D. M., Goggs, R. & Behling-Kelly, E. In vitro inhibition of canine complement-mediated hemolysis. J. Vet. Intern. Med. 32, 142\u2013146. https:\/\/doi.org\/10.1111\/jvim.14871 (2018).","journal-title":"J. Vet. Intern. Med."},{"key":"37312_CR32","doi-asserted-by":"publisher","first-page":"104735","DOI":"10.1016\/j.jprot.2022.104735","volume":"270","author":"P Bili\u0107","year":"2023","unstructured":"Bili\u0107, P. et al. Serum and urine profiling by high-throughput TMT-based proteomics for the investigation of renal dysfunction in canine babesiosis. J. Proteomics 270, 104735. https:\/\/doi.org\/10.1016\/j.jprot.2022.104735 (2023).","journal-title":"J. Proteomics"},{"key":"37312_CR33","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/aps.2013.200","volume":"35","author":"T Siqueiros-Cend\u00f3n","year":"2014","unstructured":"Siqueiros-Cend\u00f3n, T. et al. Immunomodulatory effects of lactoferrin. Acta Pharmacol. Sin. 35, 557\u2013566. https:\/\/doi.org\/10.1038\/aps.2013.200 (2014).","journal-title":"Acta Pharmacol. Sin."},{"key":"37312_CR34","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1515\/cclm.1999.049","volume":"37","author":"S Baveye","year":"1999","unstructured":"Baveye, S., Elass, E., Mazurier, J., Spik, G. & Legrand, D. Lactoferrin: A multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin. Chem. Lab. Med. 37, 281\u2013286. https:\/\/doi.org\/10.1515\/cclm.1999.049 (1999).","journal-title":"Clin. Chem. Lab. Med."},{"key":"37312_CR35","doi-asserted-by":"publisher","first-page":"H2385","DOI":"10.1152\/ajpheart.00092.2021","volume":"320","author":"J Wang","year":"2021","unstructured":"Wang, J. et al. Mechanistic insights into cell-free hemoglobin-induced injury during septic shock. Am. J. Physiol. Heart Circ. Physiol. 320, H2385-h2400. https:\/\/doi.org\/10.1152\/ajpheart.00092.2021 (2021).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"37312_CR36","doi-asserted-by":"publisher","first-page":"3628","DOI":"10.1111\/trf.15567","volume":"59","author":"KE Remy","year":"2019","unstructured":"Remy, K. E. et al. Haptoglobin therapy has differential effects depending on severity of canine septic shock and cell-free hemoglobin level. Transfusion 59, 3628\u20133638. https:\/\/doi.org\/10.1111\/trf.15567 (2019).","journal-title":"Transfusion"},{"key":"37312_CR37","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1007\/s00018-005-5372-0","volume":"62","author":"P Valenti","year":"2005","unstructured":"Valenti, P. & Antonini, G. Lactoferrin: An important host defence against microbial and viral attack. Cell Mol. Life Sci. 62, 2576\u20132587. https:\/\/doi.org\/10.1007\/s00018-005-5372-0 (2005).","journal-title":"Cell Mol. Life Sci."},{"key":"37312_CR38","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/978-0-387-74087-4_6","volume":"606","author":"D Legrand","year":"2008","unstructured":"Legrand, D. et al. Lactoferrin structure and functions. Adv. Exp. Med. Biol. 606, 163\u2013194. https:\/\/doi.org\/10.1007\/978-0-387-74087-4_6 (2008).","journal-title":"Adv. Exp. Med. Biol."},{"key":"37312_CR39","doi-asserted-by":"publisher","first-page":"710","DOI":"10.4269\/ajtmh.2005.73.710","volume":"73","author":"H Ikadai","year":"2005","unstructured":"Ikadai, H. et al. Inhibitory effect of lactoferrin on in vitro growth of Babesia caballi. Am. J. Trop. Med. Hyg. 73, 710\u2013712 (2005).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"37312_CR40","doi-asserted-by":"publisher","first-page":"3821","DOI":"10.2147\/dddt.S77860","volume":"9","author":"N Anand","year":"2015","unstructured":"Anand, N. et al. Effect of lactoferrin protein on red blood cells and macrophages: Mechanism of parasite-host interaction. Drug Des. Dev. Ther. 9, 3821\u20133835. https:\/\/doi.org\/10.2147\/dddt.S77860 (2015).","journal-title":"Drug Des. Dev. Ther."},{"key":"37312_CR41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","volume":"42","author":"YC Lu","year":"2008","unstructured":"Lu, Y. C., Yeh, W. C. & Ohashi, P. S. LPS\/TLR4 signal transduction pathway. Cytokine 42, 145\u2013151. https:\/\/doi.org\/10.1016\/j.cyto.2008.01.006 (2008).","journal-title":"Cytokine"},{"key":"37312_CR42","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1111\/j.1742-4658.2010.07620.x","volume":"277","author":"K Ando","year":"2010","unstructured":"Ando, K. et al. Human lactoferrin activates NF-kappaB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaccharide-stimulated TLR4 signaling. FEBS J. 277, 2051\u20132066. https:\/\/doi.org\/10.1111\/j.1742-4658.2010.07620.x (2010).","journal-title":"FEBS J."},{"key":"37312_CR43","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cca.2007.02.025","volume":"381","author":"I Angriman","year":"2007","unstructured":"Angriman, I. et al. Enzymes in feces: Useful markers of chronic inflammatory bowel disease. Clin. Chim. Acta 381, 63\u201368. https:\/\/doi.org\/10.1016\/j.cca.2007.02.025 (2007).","journal-title":"Clin. Chim. Acta"},{"key":"37312_CR44","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1186\/s12864-021-07889-4","volume":"22","author":"RL Smith","year":"2021","unstructured":"Smith, R. L. et al. Experimental Babesia rossi infection induces hemolytic, metabolic, and viral response pathways in the canine host. BMC Genomics 22, 619. https:\/\/doi.org\/10.1186\/s12864-021-07889-4 (2021).","journal-title":"BMC Genomics"},{"key":"37312_CR45","doi-asserted-by":"publisher","first-page":"715701","DOI":"10.3389\/fmicb.2021.715701","volume":"12","author":"J Kule\u0161","year":"2021","unstructured":"Kule\u0161, J. et al. Combined untargeted and targeted metabolomics approaches reveal urinary changes of amino acids and energy metabolism in canine babesiosis with different levels of kidney function. Front. Microbiol. 12, 715701. https:\/\/doi.org\/10.3389\/fmicb.2021.715701 (2021).","journal-title":"Front. Microbiol."},{"key":"37312_CR46","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0248-4900(91)90010-k","volume":"73","author":"A Valentin","year":"1991","unstructured":"Valentin, A. et al. Lipid trafficking between high density lipoproteins and Babesia divergens-infected human erythrocytes. Biol. Cell 73, 63\u201370. https:\/\/doi.org\/10.1016\/0248-4900(91)90010-k (1991).","journal-title":"Biol. Cell"},{"key":"37312_CR47","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1111\/jvim.15537","volume":"33","author":"Z Milanovi\u0107","year":"2019","unstructured":"Milanovi\u0107, Z. et al. Association of acute Babesia canis infection and serum lipid, lipoprotein, and apoprotein concentrations in dogs. J. Vet. Intern. Med. 33, 1686\u20131694. https:\/\/doi.org\/10.1111\/jvim.15537 (2019).","journal-title":"J. Vet. Intern. Med."},{"key":"37312_CR48","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.cimid.2016.10.002","volume":"49","author":"D Escribano","year":"2016","unstructured":"Escribano, D. et al. Serum apolipoprotein-A1 as a possible biomarker for monitoring treatment of canine leishmaniosis. Comp. Immunol. Microbiol. Infect. Dis. 49, 82\u201387. https:\/\/doi.org\/10.1016\/j.cimid.2016.10.002 (2016).","journal-title":"Comp. Immunol. Microbiol. Infect. Dis."},{"key":"37312_CR49","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3389\/fvets.2020.00263","volume":"7","author":"M Giunti","year":"2020","unstructured":"Giunti, M., Grossi, G., Tro\u00eda, R., Fracassi, F. & Dondi, F. Evaluation of serum apolipoprotein A1 in canine sepsis. Front. Vet. Sci. 7, 263. https:\/\/doi.org\/10.3389\/fvets.2020.00263 (2020).","journal-title":"Front. Vet. Sci."},{"key":"37312_CR50","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/0005-2760(83)90047-4","volume":"750","author":"YL Marcel","year":"1983","unstructured":"Marcel, Y. L., Vezina, C. & Milne, R. W. Cholesteryl ester and apolipoprotein E transfer between human high density lipoproteins and chylomicrons. Biochim. Biophys. Acta 750, 411\u2013417. https:\/\/doi.org\/10.1016\/0005-2760(83)90047-4 (1983).","journal-title":"Biochim. Biophys. Acta"},{"key":"37312_CR51","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1172\/jci28632","volume":"116","author":"RW Mahley","year":"2006","unstructured":"Mahley, R. W., Huang, Y. & Weisgraber, K. H. Putting cholesterol in its place: apoE and reverse cholesterol transport. J. Clin. Invest. 116, 1226\u20131229. https:\/\/doi.org\/10.1172\/jci28632 (2006).","journal-title":"J. Clin. Invest."},{"key":"37312_CR52","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.ccc.2005.08.008","volume":"22","author":"PE Marik","year":"2006","unstructured":"Marik, P. E. Dyslipidemia in the critically ill. Crit. Care Clin. 22, 151\u2013159. https:\/\/doi.org\/10.1016\/j.ccc.2005.08.008 (2006).","journal-title":"Crit. Care Clin."},{"key":"37312_CR53","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1111\/jvim.16420","volume":"36","author":"E Behling-Kelly","year":"2022","unstructured":"Behling-Kelly, E. et al. Acute phase protein response and changes in lipoprotein particle size in dogs with systemic inflammatory response syndrome. J. Vet. Intern. Med. 36, 993\u20131004. https:\/\/doi.org\/10.1111\/jvim.16420 (2022).","journal-title":"J. Vet. Intern. Med."},{"key":"37312_CR54","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1194\/jlr.R300019-JLR200","volume":"45","author":"W Khovidhunkit","year":"2004","unstructured":"Khovidhunkit, W. et al. Effects of infection and inflammation on lipid and lipoprotein metabolism: Mechanisms and consequences to the host. J. Lipid Res. 45, 1169\u20131196. https:\/\/doi.org\/10.1194\/jlr.R300019-JLR200 (2004).","journal-title":"J. Lipid Res."},{"key":"37312_CR55","doi-asserted-by":"publisher","first-page":"1880","DOI":"10.1161\/CIRCRESAHA.114.302805","volume":"114","author":"RS Rosenson","year":"2014","unstructured":"Rosenson, R. S., Brewer, H. B. & Rader, D. J. Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome. Circ. Res. 114, 1880\u20131889. https:\/\/doi.org\/10.1161\/CIRCRESAHA.114.302805 (2014).","journal-title":"Circ. Res."},{"key":"37312_CR56","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1161\/01.ATV.0000105902.89459.09","volume":"24","author":"P Delafontaine","year":"2004","unstructured":"Delafontaine, P., Song, Y.-H. & Li, Y. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arterioscler. Thromb. Vasc. Biol. 24, 435\u2013444. https:\/\/doi.org\/10.1161\/01.ATV.0000105902.89459.09 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"37312_CR57","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1128\/mmbr.00031-10","volume":"75","author":"M Cargnello","year":"2011","unstructured":"Cargnello, M. & Roux, P. P. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol. Mol. Biol. Rev. 75, 50\u201383. https:\/\/doi.org\/10.1128\/mmbr.00031-10 (2011).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"37312_CR58","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1152\/physrev.1999.79.1.143","volume":"79","author":"C Widmann","year":"1999","unstructured":"Widmann, C., Gibson, S., Jarpe, M. B. & Johnson, G. L. Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiol. Rev. 79, 143\u2013180. https:\/\/doi.org\/10.1152\/physrev.1999.79.1.143 (1999).","journal-title":"Physiol. Rev."},{"key":"37312_CR59","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nrm1130","volume":"4","author":"R Timpl","year":"2003","unstructured":"Timpl, R., Sasaki, T., Kostka, G. & Chu, M.-L. Fibulins: A versatile family of extracellular matrix proteins. Nat. Rev. Mol. Cell Biol. 4, 479\u2013489. https:\/\/doi.org\/10.1038\/nrm1130 (2003).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"37312_CR60","doi-asserted-by":"publisher","first-page":"4587","DOI":"10.1242\/jcs.114.24.4587","volume":"114","author":"WO Twal","year":"2001","unstructured":"Twal, W. O. et al. Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility. J. Cell Sci. 114, 4587\u20134598. https:\/\/doi.org\/10.1242\/jcs.114.24.4587 (2001).","journal-title":"J. Cell Sci."},{"key":"37312_CR61","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1182\/blood.V88.7.2569.bloodjournal8872569","volume":"88","author":"S Godyna","year":"1996","unstructured":"Godyna, S., Diaz-Ricart, M. & Argraves, W. Fibulin-1 mediates platelet adhesion via a bridge of fibrinogen. Blood 88, 2569\u20132577. https:\/\/doi.org\/10.1182\/blood.V88.7.2569.bloodjournal8872569 (1996).","journal-title":"Blood"},{"key":"37312_CR62","doi-asserted-by":"publisher","first-page":"e101522","DOI":"10.1371\/journal.pone.0101522","volume":"9","author":"R Kruger","year":"2014","unstructured":"Kruger, R. et al. Extracellular matrix biomarker, fibulin-1, is closely related to NT-proBNP and soluble urokinase plasminogen activator receptor in patients with aortic valve stenosis (The SEAS Study). PLoS ONE 9, e101522. https:\/\/doi.org\/10.1371\/journal.pone.0101522 (2014).","journal-title":"PLoS ONE"},{"key":"37312_CR63","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1111\/jvim.12146","volume":"27","author":"R Bari\u0107 Rafaj","year":"2013","unstructured":"Bari\u0107 Rafaj, R. et al. Markers of coagulation activation, endothelial stimulation, and inflammation in dogs with babesiosis. J. Vet. Intern. Med. 27, 1172\u20131178. https:\/\/doi.org\/10.1111\/jvim.12146 (2013).","journal-title":"J. Vet. Intern. Med."},{"key":"37312_CR64","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1055\/s-0037-1615841","volume":"82","author":"D Collen","year":"1999","unstructured":"Collen, D. The plasminogen (fibrinolytic) system. Thromb. Haemost. 82, 259\u2013270 (1999).","journal-title":"Thromb. Haemost."},{"key":"37312_CR65","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1186\/s12917-017-0995-6","volume":"13","author":"J Kule\u0161","year":"2017","unstructured":"Kule\u0161, J., Goti\u0107, J., Mrljak, V. & Bari\u0107 Rafaj, R. Blood markers of fibrinolysis and endothelial activation in canine babesiosis. BMC Vet. Res. 13, 82. https:\/\/doi.org\/10.1186\/s12917-017-0995-6 (2017).","journal-title":"BMC Vet. Res."},{"key":"37312_CR66","doi-asserted-by":"publisher","first-page":"e35227","DOI":"10.1371\/journal.pone.0035227","volume":"7","author":"M Asada","year":"2012","unstructured":"Asada, M. et al. Gliding motility of Babesia bovis merozoites visualized by time-lapse video microscopy. PLoS ONE 7, e35227. https:\/\/doi.org\/10.1371\/journal.pone.0035227 (2012).","journal-title":"PLoS ONE"},{"key":"37312_CR67","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1097\/00003246-200301000-00024","volume":"31","author":"B Dahl","year":"2003","unstructured":"Dahl, B. et al. Plasma concentration of Gc-globulin is associated with organ dysfunction and sepsis after injury. Crit. Care Med. 31, 152\u2013156. https:\/\/doi.org\/10.1097\/00003246-200301000-00024 (2003).","journal-title":"Crit. Care Med."},{"key":"37312_CR68","doi-asserted-by":"publisher","first-page":"H2487","DOI":"10.1152\/ajpheart.00589.2007","volume":"293","author":"PC Minneci","year":"2007","unstructured":"Minneci, P. C. et al. A canine model of septic shock: Balancing animal welfare and scientific relevance. Am. J. Physiol. Heart Circ. Physiol. 293, H2487-2500. https:\/\/doi.org\/10.1152\/ajpheart.00589.2007 (2007).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"37312_CR69","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","volume":"18","author":"N Percie du Sert","year":"2020","unstructured":"Percie du Sert, N. et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol. 18, e3000410. https:\/\/doi.org\/10.1371\/journal.pbio.3000410 (2020).","journal-title":"PLoS Biol."},{"key":"37312_CR70","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.vetpar.2008.04.012","volume":"155","author":"PT Matjila","year":"2008","unstructured":"Matjila, P. T., Leisewitz, A. L., Jongejan, F. & Penzhorn, B. L. Molecular detection of tick-borne protozoal and ehrlichial infections in domestic dogs in South Africa. Vet. Parasitol. 155, 152\u2013157. https:\/\/doi.org\/10.1016\/j.vetpar.2008.04.012 (2008).","journal-title":"Vet. Parasitol."},{"key":"37312_CR71","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jprot.2018.08.009","volume":"192","author":"A Horvati\u0107","year":"2019","unstructured":"Horvati\u0107, A. et al. Quantitative proteomics using tandem mass tags in relation to the acute phase protein response in chicken challenged with Escherichia coli lipopolysaccharide endotoxin. J. Proteomics 192, 64\u201377. https:\/\/doi.org\/10.1016\/j.jprot.2018.08.009 (2019).","journal-title":"J. Proteomics"},{"key":"37312_CR72","unstructured":"R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2020)."},{"key":"37312_CR73","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H Wickham","year":"2016","unstructured":"Wickham, H. ggplot2: Elegant Graphics for Data Analysis (Springer-Verlag, 2016)."},{"key":"37312_CR74","doi-asserted-by":"publisher","first-page":"e86","DOI":"10.1002\/cpbi.86","volume":"68","author":"J Chong","year":"2019","unstructured":"Chong, J., Wishart, D. S. & Xia, J. Using MetaboAnalyst 4.0 for comprehensive and integrative metabolomics data analysis. Curr. Protoc. Bioinform. 68, e86. https:\/\/doi.org\/10.1002\/cpbi.86 (2019).","journal-title":"Curr. Protoc. Bioinform."},{"key":"37312_CR75","doi-asserted-by":"publisher","first-page":"D480","DOI":"10.1093\/nar\/gkaa1100","volume":"49","author":"The UniProt Consortium","year":"2020","unstructured":"The UniProt Consortium. UniProt: The universal protein knowledgebase in 2021. Nucleic Acids Res. 49, D480\u2013D489. https:\/\/doi.org\/10.1093\/nar\/gkaa1100 (2020).","journal-title":"Nucleic Acids Res."},{"key":"37312_CR76","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","volume":"36","author":"SX Ge","year":"2019","unstructured":"Ge, S. X., Jung, D. & Yao, R. ShinyGO: A graphical gene-set enrichment tool for animals and plants. Bioinformatics 36, 2628\u20132629. https:\/\/doi.org\/10.1093\/bioinformatics\/btz931 (2019).","journal-title":"Bioinformatics"},{"key":"37312_CR77","doi-asserted-by":"publisher","first-page":"D687","DOI":"10.1093\/nar\/gkab1028","volume":"50","author":"M Gillespie","year":"2021","unstructured":"Gillespie, M. et al. The reactome pathway knowledgebase 2022. Nucleic Acids Res. 50, D687\u2013D692. https:\/\/doi.org\/10.1093\/nar\/gkab1028 (2021).","journal-title":"Nucleic Acids Res."},{"key":"37312_CR78","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","volume":"50","author":"Y Perez-Riverol","year":"2022","unstructured":"Perez-Riverol, Y. et al. The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543\u2013D552. https:\/\/doi.org\/10.1093\/nar\/gkab1038 (2022).","journal-title":"Nucleic Acids Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-37312-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-37312-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-37312-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T17:05:21Z","timestamp":1687539921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-37312-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,23]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["37312"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-37312-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2665883\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,23]]},"assertion":[{"value":"7 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10249"}}