{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:57:59Z","timestamp":1790506679543,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2017YFD0501306"],"award-info":[{"award-number":["2017YFD0501306"]}]},{"name":"the Qinghai Science and Technology Department Project","award":["2020-ZJ-Y01"],"award-info":[{"award-number":["2020-ZJ-Y01"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Parasites Vectors"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alveolar echinococcosis (AE) is a fatal zoonosis caused by the larvae of<jats:italic>Echinococcus multilocularis<\/jats:italic>. However, current chemotherapy treatment options are based on benzimidazoles [albendazole (ABZ) and mebendazole], which have limited efficacy. Therefore, novel drugs are necessary for the treatment of this disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The anthelmintic effects of crocin were tested on<jats:italic>E. multilocularis<\/jats:italic>metacestodes, germinal cells and protoscoleces in vitro. Human foreskin fibroblasts (HFFs) and Reuber rat hepatoma (RH) cells were used to assess cytotoxicity. The in vivo efficacy of crocin was investigated in mice following secondary infection with<jats:italic>E. multilocularis<\/jats:italic>. Furthermore, collagen deposition and degradation in host tissues around the metacestodes were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro, crocin had a median effective concentration of 11.36\u00a0\u03bcM against cultured<jats:italic>E. multilocularis<\/jats:italic>metacestodes, while it reduced germinal cell viability at a median inhibitory concentration of 10.05\u00a0\u03bcM. Crocin was less toxic to HFFs and RH mammalian cell lines than to metacestodes. Transmission electron microscopy revealed that crocin treatment resulted in structural damage in the germinal layer. In addition, 60.33\u2009\u00b1\u20093.06% of protoscoleces were killed by treatment with 10\u00a0\u03bcM crocin for 7\u00a0days, indicating that crocin has a parasiticidal effect. In vivo, the metacestode weight was significantly reduced after the administration of crocin at 50\u00a0mg\/kg and 100\u00a0mg\/kg (55.1 and 68.1%, respectively). Metacestode pathology showed structural disruption of the germinal and laminated layers after crocin treatment. The crocin- and ABZ-treated groups presented significant increases in the levels of interleukin (IL)-2 and IL-4. Furthermore, crocin inhibited the expression of matrix metalloproteinases (MMPs) (MMP2 and MMP9) and promoted collagen deposition in the metacestode.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Crocin was demonstrated to exert parasiticidal activity against<jats:italic>E. multilocularis<\/jats:italic>in vitro and in vivo, and can be developed as a novel drug for the treatment of AE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Graphical abstract<\/jats:title><\/jats:sec>","DOI":"10.1186\/s13071-021-04866-4","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T13:03:26Z","timestamp":1626181406000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["In vivo and in vitro efficacy of crocin against Echinococcus multilocularis"],"prefix":"10.1186","volume":"14","author":[{"given":"Chuanchuan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haining","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ri-li","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"issue":"1","key":"4866_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1186\/s13256-016-1115-0","volume":"10","author":"S Spahn","year":"2016","unstructured":"Spahn S, Helmchen B, Zingg U. Alveolar echinococcosis of the right adrenal gland: a case report and review of the literature. J Med Case Rep. 2016;10(1):325.","journal-title":"J Med Case Rep"},{"issue":"1","key":"4866_CR2","doi-asserted-by":"publisher","first-page":"149","DOI":"10.5152\/eurasianjmed.2015.15003","volume":"48","author":"G Atalan","year":"2016","unstructured":"Atalan G, Sivrioglu AK, S\u00f6nmez G, S\u00f6nmez G, Celik M, Simsek B. A case of alveolar echinococcosis presenting as cerebral and spinal intradural metastases. Eurasian J Med. 2016;48(1):149\u201352.","journal-title":"Eurasian J Med"},{"key":"4866_CR3","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1051\/parasite\/2014073","volume":"21","author":"A Hemphill","year":"2014","unstructured":"Hemphill A, Stadelmann B, Rufener R, Spiliotis M, Boubaker G, M\u00fcller J, et al. Treatment of echinococcosis: albendazole and mebendazole\u2013what else. Parasite. 2014;21:70.","journal-title":"Parasite"},{"issue":"14","key":"4866_CR4","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1017\/S0031182018000719","volume":"145","author":"T Laurim\u00e4e","year":"2018","unstructured":"Laurim\u00e4e T, Kinkar L, Moks E, Romig T, Omer RA, Casulli A, et al. Molecular phylogeny based on six nuclear genes suggests that Echinococcus granulosus sensu lato genotypes G6\/G7 and G8\/G10 can be regarded as two distinct species. Parasitology. 2018;145(14):1929\u201337.","journal-title":"Parasitology."},{"issue":"2","key":"4866_CR5","doi-asserted-by":"publisher","first-page":"e00075","DOI":"10.1128\/CMR.00075-18","volume":"32","author":"H Wen","year":"2019","unstructured":"Wen H, Vuitton L, Tuxun T, Li J, Vuitton DA, Zhang WB, et al. Echinococcosis: advances in the 21st century. Clin Microbiol Rev. 2019;32(2):e00075-e118.","journal-title":"Clin Microbiol Rev"},{"key":"4866_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2020.11.010","author":"ID Woolsey","year":"2020","unstructured":"Woolsey ID, Miller AL. Echinococcus granulosus sensu lato and Echinococcus multilocularis: a review. Res Vet Sci. 2020. https:\/\/doi.org\/10.1016\/j.rvsc.2020.11.010.","journal-title":"Res Vet Sci"},{"key":"4866_CR7","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/bs.apar.2016.09.006","volume":"96","author":"P Kern","year":"2017","unstructured":"Kern P, Menezes da Silva A, Akhan O, M\u00fcllhaupt B, Vizcaychipi KA, Budke C, et al. The echinococcoses: diagnosis, clinical management and burden of disease. Adv Parasitol. 2017;96:259\u2013369.","journal-title":"Adv Parasitol."},{"key":"4866_CR8","doi-asserted-by":"publisher","first-page":"e00040","DOI":"10.1016\/j.fawpar.2019.e00040","volume":"15","author":"B Lundstr\u00f6m-Stadelmann","year":"2019","unstructured":"Lundstr\u00f6m-Stadelmann B, Rufener R, Ritler D, Zurbriggen R, Hemphill A. The importance of being parasiticidal\u2026an update on drug development for the treatment of alveolar echinococcosis. Food Waterborne Parasitol. 2019;15:e00040.","journal-title":"Food Waterborne Parasitol."},{"issue":"4","key":"4866_CR9","doi-asserted-by":"publisher","first-page":"e0006422","DOI":"10.1371\/journal.pntd.0006422","volume":"12","author":"M Siles-Lucas","year":"2018","unstructured":"Siles-Lucas M, Casulli A, Cirilli R, Carmena D. Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: compounds and therapeutic targets. PLoS Negl Trop Dis. 2018;12(4):e0006422.","journal-title":"PLoS Negl Trop Dis."},{"issue":"1","key":"4866_CR10","first-page":"3","volume":"23","author":"A Veisi","year":"2020","unstructured":"Veisi A, Akbari G, Mard SA, Badfar G, Zarezade V, Mirshekar MA. Role of crocin in several cancer cell lines: an updated review. Iran J Basic Med Sci. 2020;23(1):3\u201312.","journal-title":"Iran J Basic Med Sci"},{"issue":"11","key":"4866_CR11","doi-asserted-by":"publisher","first-page":"4464","DOI":"10.21037\/jtd.2019.11.18","volume":"11","author":"SS Chen","year":"2019","unstructured":"Chen SS, Gu Y, Lu F, Qian DP, Dong TT, Ding ZH, et al. Antiangiogenic effect of crocin on breast cancer cell MDA-MB-231. J Thorac Dis. 2019;11(11):4464\u201373.","journal-title":"J Thorac Dis."},{"issue":"1","key":"4866_CR12","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1080\/13880209.2018.1448874","volume":"56","author":"W Liu","year":"2018","unstructured":"Liu W, Sun Y, Cheng Z, Guo Y, Liu PM, Wen Y. Crocin exerts anti-inflammatory and anti-arthritic effects on type II collagen-induced arthritis in rats. Pharm Biol. 2018;56(1):209\u201316.","journal-title":"Pharm Biol"},{"issue":"1","key":"4866_CR13","doi-asserted-by":"publisher","first-page":"121","DOI":"10.2174\/1574892810666151102110248","volume":"11","author":"A Amin","year":"2016","unstructured":"Amin A, Hamza AA, Daoud S, Khazanehdari K, Hrout AA, Baig B, et al. Saffron-based crocin prevents early lesions of liver cancer: in vivo, in vitro and network analyses. Recent Pat Anticancer Drug Discov. 2016;11(1):121\u201333.","journal-title":"Recent Pat Anticancer Drug Discov"},{"issue":"10","key":"4866_CR14","doi-asserted-by":"publisher","first-page":"9799","DOI":"10.1007\/s11356-016-6195-2","volume":"23","author":"M Boussabbeh","year":"2016","unstructured":"Boussabbeh M, Ben Salem I, Belguesmi F, Neffati F, Najjar MF, Abid-Essefi S, et al. Crocin protects the liver and kidney from patulin-induced apoptosis in vivo. Environ Sci Pollut Res Int. 2016;23(10):9799\u2013808.","journal-title":"Environ Sci Pollut Res Int"},{"issue":"5","key":"4866_CR15","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.3906\/sag-1506-108","volume":"46","author":"\u00d6 Hazman","year":"2016","unstructured":"Hazman \u00d6, Aksoy L, B\u00fcy\u00fckben A. Effects of crocin on experimental obesity and type-2 diabetes. Turk J Med Sci. 2016;46(5):1593\u2013602.","journal-title":"Turk J Med Sci"},{"issue":"6","key":"4866_CR16","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.3109\/14756366.2014.1001755","volume":"30","author":"C De Monte","year":"2015","unstructured":"De Monte C, Bizzarri B, Gidaro MC, Carradori S, Mollica A, Luisi G, et al. Bioactive compounds of Crocus sativus L. and their semi-synthetic derivatives as promising anti-Helicobacter pylori, anti-malarial and anti-leishmanial agents. J Enzyme Inhib Med Chem. 2015;30(6):1027\u201333.","journal-title":"J Enzyme Inhib Med Chem."},{"issue":"1","key":"4866_CR17","first-page":"39","volume":"32","author":"HA Bakshi","year":"2017","unstructured":"Bakshi HA, Hakkim FL, Sam S, Javid F, Rashan L. Dietary crocin reverses melanoma metastasis. J Biomed Res. 2017;32(1):39\u201350.","journal-title":"J Biomed Res"},{"issue":"2","key":"4866_CR18","first-page":"553","volume":"17","author":"BS Yousefsani","year":"2018","unstructured":"Yousefsani BS, Mehri S, Pourahmad J, Hosseinzadeh H. Crocin prevents sub-cellular organelle damage, proteolysis and apoptosis in rat hepatocytes: a justification for its hepatoprotection. Iran J Pharm Res. 2018;17(2):553\u201362.","journal-title":"Iran J Pharm Res"},{"key":"4866_CR19","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.reth.2020.09.002","volume":"15","author":"S Nitta","year":"2020","unstructured":"Nitta S, Hisasue M, Horiguchi Y, Yamada Y, Kikuchi K, Kubo T, et al. Three-dimensional spheroid culture of canine hepatocyte-like cells derived from bone marrow mesenchymal stem cells. Regen Ther. 2020;15:210\u20135.","journal-title":"Regen Ther"},{"issue":"3","key":"4866_CR20","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/jac\/dkp490","volume":"65","author":"B Stadelmann","year":"2010","unstructured":"Stadelmann B, Scholl S, M\u00fcller J, Hemphill A. Application of an in vitro drug screening assay based on the release of phosphoglucose isomerase to determine the structure-activity relationship of thiazolides against Echinococcus multilocularis metacestodes. J Antimicrob Chemother. 2010;65(3):512\u20139.","journal-title":"J Antimicrob Chemother"},{"issue":"12","key":"4866_CR21","doi-asserted-by":"publisher","first-page":"e3352","DOI":"10.1371\/journal.pntd.0003352","volume":"8","author":"B Stadelmann","year":"2014","unstructured":"Stadelmann B, Aeschbacher D, Huber C, Spiliotis M, M\u00fcller J, Hemphill A. Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes. PLoS Negl Trop Dis. 2014;8(12):e3352.","journal-title":"PLoS Negl Trop Dis."},{"issue":"3","key":"4866_CR22","doi-asserted-by":"publisher","first-page":"e0004535","DOI":"10.1371\/journal.pntd.0004535","volume":"10","author":"B Stadelmann","year":"2016","unstructured":"Stadelmann B, Rufener R, Aeschbacher D, Spiliotis M, Gottstein B, Hemphill A. Screening of the open source malaria box reveals an early lead compound for the treatment of alveolar echinococcosis. PLoS Negl Trop Dis. 2016;10(3):e0004535.","journal-title":"PLoS Negl Trop Dis."},{"issue":"8\u20139","key":"4866_CR23","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.ijpara.2007.11.002","volume":"38","author":"M Spiliotis","year":"2008","unstructured":"Spiliotis M, Lechner S, Tappe D, Scheller C, Krohne G, Brehm K. Transient transfection of Echinococcus multilocularis primary cells and complete in vitro regeneration of metacestode vesicles. Int J Parasitol. 2008;38(8\u20139):1025\u201339.","journal-title":"Int J Parasitol"},{"key":"4866_CR24","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.actatropica.2014.08.007","volume":"140","author":"AC Mar\u00eda","year":"2014","unstructured":"Mar\u00eda AC, Celina EM. Efficacy of albendazole in combination with thymol against Echinococcus multilocularis protoscoleces and metacestodes. Acta Trop. 2014;140:61\u20137.","journal-title":"Acta Trop"},{"issue":"5","key":"4866_CR25","doi-asserted-by":"publisher","first-page":"e0126009","DOI":"10.1371\/journal.pone.0126009","volume":"10","author":"JA Loos","year":"2015","unstructured":"Loos JA, Cumino AC. In vitro anti-echinococcal and metabolic effects of metformin involve activation of AMP-activated protein kinase in larval stages of Echinococcus granulosus. PLoS ONE. 2015;10(5):e0126009.","journal-title":"PLoS ONE."},{"issue":"4","key":"4866_CR26","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.jviscsurg.2019.01.002","volume":"156","author":"M Moazeni","year":"2019","unstructured":"Moazeni M, Hosseini SV, Al-Qanbar MH, Alavi AM, Khazraei H. In vitro evaluation of the protoscolicidal effect of Eucalyptus globulus essential oil on protoscolices of hydatid cyst compared with hypertonic saline, povidone iodine and silver nitrate. J Visc Surg. 2019;156(4):291\u20135.","journal-title":"J Visc Surg"},{"issue":"6","key":"4866_CR27","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008;3(6):1101\u20138.","journal-title":"Nat Protoc"},{"key":"4866_CR28","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.ijcard.2016.11.202","volume":"228","author":"JC Liu","year":"2017","unstructured":"Liu JC, Wang F, Xie ML, Cheng ZQ, Qin Q, Chen L, et al. Osthole inhibits the expressions of collagen I and III through Smad signaling pathway after treatment with TGF-\u03b21 in mouse cardiac fibroblasts. Int J Cardiol. 2017;228:388\u201393.","journal-title":"Int J Cardiol."},{"issue":"1","key":"4866_CR29","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1186\/s13071-019-3653-y","volume":"12","author":"Y Shi","year":"2019","unstructured":"Shi Y, Wan X, Wang Z, Li J, Jiang ZH, Yang YC. First description of Echinococcus ortleppi infection in China. Parasites Vectors. 2019;12(1):398.","journal-title":"Parasites Vectors"},{"issue":"27","key":"4866_CR30","doi-asserted-by":"publisher","first-page":"e7137","DOI":"10.1097\/MD.0000000000007137","volume":"96","author":"Y Cairang","year":"2017","unstructured":"Cairang Y, Zhang L, Ren B, Ren L, Hou LZ, Wang HJ, et al. Efficacy and safety of ultrasound-guided percutaneous microwave ablation for the treatment of hepatic alveolar echinococcosis: a preliminary study. Medicine. 2017;96(27):e7137.","journal-title":"Medicine."},{"issue":"3\u20134","key":"4866_CR31","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.vetpar.2015.06.030","volume":"212","author":"CM Albani","year":"2015","unstructured":"Albani CM, Pensel PE, Elissondo N, Gambino G, Elssondo MC. In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis. Vet Parasitol. 2015;212(3\u20134):193\u20139.","journal-title":"Vet Parasitol"},{"issue":"13","key":"4866_CR32","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1016\/j.ijpara.2010.05.009","volume":"40","author":"B Stadelmann","year":"2010","unstructured":"Stadelmann B, Spiliotis M, M\u00fcller J, Scholl S, M\u00fcller N, Gottstein B, et al. Echinococcus multilocularis phosphoglucose isomerase (EmPGI): a glycolytic enzyme involved in metacestode growth and parasite-host cell interactions. Int J Parasitol. 2010;40(13):1563\u201374.","journal-title":"Int J Parasitol"},{"issue":"1","key":"4866_CR33","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/2041-9139-5-10","volume":"5","author":"U Koziol","year":"2014","unstructured":"Koziol U, Rauschendorfer T, Zanon Rodr\u00edguez L, Krohne G, Brehm K. The unique stem cell system of the immortal larva of the human parasite Echinococcus multilocularis. EvoDevo. 2014;5(1):10.","journal-title":"EvoDevo"},{"key":"4866_CR34","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.vetpar.2016.05.016","volume":"226","author":"M Yuan","year":"2016","unstructured":"Yuan M, Luo Y, Xin Q, Gao H, Zhang G, Jing T. Efficacy of osthole for Echinococcus granulosus in vitro and Echinococcus multilocularis in vivo. Vet Parasitol. 2016;226:38\u201343.","journal-title":"Vet Parasitol"},{"issue":"1","key":"4866_CR35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.cyto.2015.05.010","volume":"75","author":"J Zhu","year":"2015","unstructured":"Zhu J. T helper 2 (Th2) cell differentiation, type 2 innate lymphoid cell (ILC2) development and regulation of interleukin-4 (IL-4) and IL-13 production. Cytokine. 2015;75(1):14\u201324.","journal-title":"Cytokine"},{"issue":"11","key":"4866_CR36","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1046\/j.1365-3024.1997.d01-162.x","volume":"19","author":"I Emery","year":"1997","unstructured":"Emery I, Liance M, Leclerc C. Secondary Echinococcus multilocularis infection in A\/J mice: delayed metacestode development is associated with Th1 cytokine production. Parasite Immunol. 1997;19(11):493\u2013503.","journal-title":"Parasite Immunol"},{"issue":"9","key":"4866_CR37","doi-asserted-by":"publisher","first-page":"e0238909","DOI":"10.1371\/journal.pone.0238909","volume":"15","author":"F Corr\u00eaa","year":"2020","unstructured":"Corr\u00eaa F, Hidalgo C, Stoore C, Jim\u00e9nez M, Hern\u00e1ndez M, Paredes R. Cattle co-infection of Echinococcus granulosus and Fasciola hepatica results in a different systemic cytokine profile than single parasite infection. PLoS ONE. 2020;15(9):e0238909.","journal-title":"PLoS ONE."},{"key":"4866_CR38","doi-asserted-by":"crossref","first-page":"3523126","DOI":"10.1155\/2018\/3523126","volume":"2018","author":"F Zhang","year":"2018","unstructured":"Zhang F, Hu C, Cheng S, Wang S, Li B, Cao D, et al. The investigation of the effect and mechanism of Sophora moorcroftiana alkaloids in combination with albendazole on echinococcosis in an experimental rats model. Evid Based Complement Alternat Med. 2018;2018:3523126.","journal-title":"Evid Based Complement Alternat Med"},{"issue":"3","key":"4866_CR39","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1007\/s00436-015-4332-3","volume":"114","author":"B Ye","year":"2015","unstructured":"Ye B, Mehlhorn H. Discovery of microchannels in host tissues surrounding hydatid cysts. Parasitol Res. 2015;114(3):1245\u20136.","journal-title":"Parasitol Res"},{"issue":"5","key":"4866_CR40","doi-asserted-by":"publisher","first-page":"e12523","DOI":"10.1111\/pim.12523","volume":"40","author":"\u00c1 D\u00edaz","year":"2018","unstructured":"D\u00edaz \u00c1, Sagasti C, Casaravilla C. Granulomatous responses in larval taeniid infections. Parasite Immunol. 2018;40(5):e12523.","journal-title":"Parasite Immunol."},{"issue":"5","key":"4866_CR41","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3347\/kjp.2019.57.5.517","volume":"57","author":"J Yang","year":"2019","unstructured":"Yang J, Zhao Z, Li S, Chen H. A case of alveolar echinococcosis occurring in the Hilar bile duct. Korean J Parasitol. 2019;57(5):517\u201320.","journal-title":"Korean J Parasitol"},{"issue":"5","key":"4866_CR42","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1007\/s00436-010-2155-9","volume":"108","author":"RY Li","year":"2011","unstructured":"Li RY, Peng Q, Jia B, Shi GQ, Zhao ZS, Shen H, et al. Antibody and cytokine responses to hydatid in experimentally infected Kazakh sheep with hydatidosis resistance haplotype. Parasitol Res. 2011;108(5):1131\u20137.","journal-title":"Parasitol Res"},{"issue":"2","key":"4866_CR43","first-page":"110","volume":"20","author":"HB Bostan","year":"2017","unstructured":"Bostan HB, Mehri S, Hosseinzadeh H. Toxicology effects of saffron and its constituents: a review. Iran J Basic Med Sci. 2017;20(2):110\u201321.","journal-title":"Iran J Basic Med Sci"},{"issue":"5","key":"4866_CR44","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.7314\/APJCP.2012.13.5.2305","volume":"13","author":"SK Noureini","year":"2012","unstructured":"Noureini SK, Wink M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac J Cancer Prev. 2012;13(5):2305\u20139.","journal-title":"Asian Pac J Cancer Prev"},{"issue":"4","key":"4866_CR45","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1016\/j.sjbs.2016.10.007","volume":"25","author":"MM Algandaby","year":"2018","unstructured":"Algandaby MM. Antifibrotic effects of crocin on thioacetamide-induced liver fibrosis in mice. Saudi J Biol Sci. 2018;25(4):747\u201354.","journal-title":"Saudi J Biol Sci"}],"container-title":["Parasites &amp; Vectors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-021-04866-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13071-021-04866-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13071-021-04866-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T01:25:53Z","timestamp":1725413153000},"score":1,"resource":{"primary":{"URL":"https:\/\/parasitesandvectors.biomedcentral.com\/articles\/10.1186\/s13071-021-04866-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["4866"],"URL":"https:\/\/doi.org\/10.1186\/s13071-021-04866-4","relation":{},"ISSN":["1756-3305"],"issn-type":[{"value":"1756-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,13]]},"assertion":[{"value":"9 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2021","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 animal procedures were approved by the Ethics Committee of Qinghai University Affiliated Hospital (no. AF-RHEC-0018-01).","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":"We declare that we have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"364"}}