{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:32:35Z","timestamp":1790652755608,"version":"4.1.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.609994","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T08:39:24Z","timestamp":1605602364000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Arachidonic Acid Is a Safe and Efficacious Schistosomicide, and an Endoschistosomicide in Natural and Experimental Infections, and Cysteine Peptidase Vaccinated Hosts"],"prefix":"10.3389","volume":"11","author":[{"given":"Hatem","family":"Tallima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violette S.","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashika","family":"El Ridi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/s0065-308x(08)60188-8","article-title":"Ultrastructure of the tegument of Schistosoma","volume":"11","author":"Hockley","year":"1973","journal-title":"Adv Parasitol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/0020-7519(73)90004-0","article-title":"Schistosoma mansoni: changes in the outer membrane of the tegument during development from cercaria to adult worm","volume":"3","author":"Hockley","year":"1973","journal-title":"Int J Parasitol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(87)90147-2","article-title":"The phospholipid and fatty acid composition of Schistosoma mansoni and of its purified tegumental membranes","volume":"23","author":"Allan","year":"1987","journal-title":"Mol Biochem Parasitol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1017\/s0031182000066385","article-title":"Distribution and biophysical properties of fluorescent lipids on the surface of adult Schistosoma mansoni","volume":"113","author":"Redman","year":"1996","journal-title":"Parasitology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0166-6851(97)00151-5","article-title":"Interconversion of sphingomyelin and ceramide in adult Schistosoma mansoni","volume":"90","author":"Redman","year":"1997","journal-title":"Mol Biochem Parasitol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1645\/GE-3334","article-title":"Depletion of Schistosoma mansoni lung-stage schistosomula cholesterol by methyl-beta-cyclodextrin dramatically increases specific antibody binding to surface membrane antigens","volume":"90","author":"El Ridi","year":"2004","journal-title":"J Parasitol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1645\/GE-439R","article-title":"Methyl-beta-Cyclodextrin treatment and filipin staining reveal the role of cholesterol in surface membrane antigen sequestration of Schistosoma mansoni and S. haematobium lung-stage larvae","volume":"91","author":"Tallima","year":"2005","journal-title":"J Parasitol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182007003174","article-title":"Evaluation of cholesterol content and impact on antigen exposure in the outer lipid bilayer of adult schistosomes","volume":"134","author":"Tallima","year":"2007","journal-title":"Parasitology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1645\/GE-514R.1","article-title":"In vitro and in vivo effects of unsaturated fatty acids on Schistosoma mansoni and S. haematobium lung-stage larvae","volume":"91","author":"Tallima","year":"2005","journal-title":"J Parasitol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1645\/GE-745R1.1","article-title":"Equilibrium in lung schistosomula sphingomyelin breakdown and biosynthesis allows very small molecules, but not antibody, to access proteins at the host-parasite interface","volume":"92","author":"El Ridi","year":"2006","journal-title":"J Parasitol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nature08160","article-title":"The genome of the blood fluke Schistosoma mansoni","volume":"460","author":"Berriman","year":"2009","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001455","article-title":"A systematically improved high quality genome and transcriptome of the human blood fluke Schistosoma mansoni","volume":"6","author":"Protasio","year":"2012","journal-title":"PloS Negl Trop Dis"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2011.04.003","article-title":"Enzymatic activity and immunolocalization of Schistosoma mansoni and Schistosoma haematobium neutral sphingomyelinase","volume":"178","author":"Tallima","year":"2011","journal-title":"Mol Biochem Parasitol"},{"key":"B14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.5772\/55787","article-title":"Solving the Riddle of the Lung-Stage Schistosomula Paved the Way to a Novel Remedy and an Efficacious Vaccine for Schistosomiasis","volume-title":"Parasitic Diseases - Schistosomiasis","author":"El Ridi","year":"2013"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1065","article-title":"Whole-genome sequence of Schistosoma haematobium","volume":"44","author":"Young","year":"2012","journal-title":"Nat Genet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz108.1","article-title":"High-quality Schistosoma haematobium genome achieved by single-molecule and long-range sequencing","volume":"8","author":"Stroehlein","year":"2019","journal-title":"Gigascience"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2016.03.036","article-title":"Biochemical and biophysical methodologies open the road for effective schistosomiasis therapy and vaccination","volume":"186","author":"El Ridi","year":"2017","journal-title":"Biochim Biophys Acta Gen Subj"},{"key":"B18","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(17)37526-9","article-title":"Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor alpha","volume":"269","author":"Jayadev","year":"1994","journal-title":"J Biol Chem"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1997.d01-2227.x","article-title":"Activation of neutral sphingomyelinase in human neutrophils by polyunsaturated fatty acids","volume":"91","author":"Robinson","year":"1997","journal-title":"Immunology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1139\/003-091","article-title":"Acid and neutral sphingomyelinases: roles and mechanisms of regulation","volume":"82","author":"Marchesini","year":"2004","journal-title":"Biochem Cell Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00173-10","article-title":"In vitro and in vivo activities of arachidonic acid against Schistosoma mansoni and Schistosoma haematobium","volume":"54","author":"El Ridi","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.08.019","article-title":"Efficacy and mechanism of action of arachidonic acid in the treatment of hamsters infected with Schistosoma mansoni or Schistosoma haematobium","volume":"39","author":"El Ridi","year":"2012","journal-title":"Int J Antimicrob Agents"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.14-0328","article-title":"Efficacy and safety of arachidonic acid for treatment of Schistosoma mansoni-infected children in Menoufiya, Egypt","volume":"91","author":"Selim","year":"2014","journal-title":"Am J Trop Med Hyg"},{"key":"B24","doi-asserted-by":"publisher","first-page":"797","DOI":"10.4269\/ajtmh.14-0675","article-title":"Efficacy and safety of arachidonic acid for treatment of school-age children in Schistosoma mansoni high-endemicity regions","volume":"92","author":"Barakat","year":"2015","journal-title":"Am J Trop Med Hyg"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13210","article-title":"Arachidonic acid as a bioactive molecule","volume":"107","author":"Brash","year":"2001","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.9124-17","article-title":"The clinical significance of low serum arachidonic acid in sepsis patients with hypoalbuminemia","volume":"57","author":"Yamaguchi","year":"2018","journal-title":"Intern Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13129","article-title":"Ratios of serum eicosapentaenoic acid to arachidonic acid and docosahexaenoic acid to arachidonic acid were inversely associated with serum resistin levels: The Hisayama Study","volume":"11","author":"Higashioka","year":"2020","journal-title":"J Diabetes Investig"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.72.12.5130","article-title":"Increased concentrations of nonesterified arachidonic acid, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid, prostaglandin E2, and prostaglandin F2alpha in epidermis of psoriasis","volume":"72","author":"Hammarstr\u00f6m","year":"1975","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B29","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/cbf.1012","article-title":"Arachidonic acid cytotoxicity: can arachidonic acid be a physiological mediator of cell death","volume":"21","author":"Pompeia","year":"2003","journal-title":"Cell Biochem Funct"},{"key":"B30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.jare.2018.12.008","article-title":"Role of T lymphocytes and papain enzymatic activity in the protection induced by the cysteine protease against Schistosoma mansoni in mice","volume":"17","author":"Tallima","year":"2019","journal-title":"J Adv Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2016.07.026","article-title":"Toxicological evaluation of arachidonic acid (ARA)-rich oil and docosahexaenoic acid (DHA)-rich oil","volume":"96","author":"Lewis","year":"2016","journal-title":"Food Chem Toxicol"},{"key":"B32","article-title":"Praziquantel and arachidonic acid combination. Innovative approach to the Treatment of Schistosomiasis. IN: An Overview of Tropical Diseases edited by: Samie Amidou","author":"Tallima","year":"2015"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw506","article-title":"Reduced efficacy of praziquantel against Schistosoma mansoni is associated with multiple rounds of mass drug administration","volume":"63","author":"Crellen","year":"2016","journal-title":"Clin Infect Dis"},{"key":"B34","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s40249-018-0448-x","article-title":"Efficacy of praziquantel treatment regimens in pre-school and school aged children infected with schistosomiasis in sub-Saharan Africa: a systematic review","volume":"7","author":"Kabuyaya","year":"2018","journal-title":"Infect Dis Poverty"},{"key":"B35","unstructured":"HadleyK El RidiR Compositions and methods for the prevention and\/or treatment of schistosomiasis."},{"key":"B36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jare.2018.03.005","article-title":"Synopsis of arachidonic acid metabolism: A review","volume":"11","author":"Hanna","year":"2018","journal-title":"J Adv Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2018.03.004","article-title":"Omega-6 fatty acids and inflammation","volume":"132","author":"Innes","year":"2018","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114519000692","article-title":"A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans","volume":"121","author":"Calder","year":"2019","journal-title":"Br J Nutr"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166979","article-title":"Natural Schistosoma mansoni infection in the wild reservoir Nectomys squamipes leads to excessive lipid droplet accumulation in hepatocytes in the absence of liver functional impairment","volume":"11","author":"Amaral","year":"2016","journal-title":"PloS One"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184696","article-title":"Histological assessment of granulomas in natural and experimental Schistosoma mansoni infections using whole slide imaging","volume":"12","author":"Amaral","year":"2017","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2018.01.005","article-title":"Is arachidonic acid an endoschistosomicide","volume":"11","author":"Hanna","year":"2018","journal-title":"J Adv Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2019.105186","article-title":"Comparative serum metabolomics between SCID mice and BALB\/c mice with or without Schistosoma japonicum infection: Clues to the abnormal growth and development of schistosome in SCID mice","volume":"200","author":"Liu","year":"2019","journal-title":"Acta Trop"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.9b00034","article-title":"Antischistosomal properties of sclareol and its heck-coupled derivatives: design, synthesis, biological evaluation, and untargeted metabolomics","volume":"5","author":"Crusco","year":"2019","journal-title":"ACS Infect Dis"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.05.005","article-title":"Uptake of Schistosoma mansoni extracellular vesicles by human endothelial and monocytic cell lines and impact on vascular endothelial cell gene expression","volume":"50","author":"Kifle","year":"2020","journal-title":"Int J Parasitol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jare.2018.01.001","article-title":"Arachidonic acid and other unsaturated fatty acids and some of their metabolites function as endogenous antimicrobial molecules: A review","volume":"11","author":"Das","year":"2018","journal-title":"J Adv Res"},{"key":"B46","first-page":"2020","article-title":"Resistance of Biomphalaria alexandrina to Schistosoma mansoni and Bulinus truncatus to Schistosoma haematobium correlates with unsaturated fatty acid levels in the snail soft tissue","volume-title":"J Parasitol Res","author":"Elias","year":"2020"},{"key":"B47","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1645\/GE-3186.1","article-title":"Vaccine-induced protection against murine schistosomiasis mansoni with larval excretory-secretory antigens and papain or type-2 cytokines","volume":"99","author":"El Ridi","year":"2013","journal-title":"J Parasitol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085401","article-title":"Cysteine peptidases as schistosomiasis vaccines with inbuilt adjuvanticity","volume":"9","author":"El Ridi","year":"2014","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2014.00119","article-title":"Induction of protective immune responses against schistosomiasis using functionally active cysteine peptidases","volume":"5","author":"El Ridi","year":"2014","journal-title":"Front Genet"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00130","article-title":"Induction of protective immune responses against schistosomiasis haematobium in hamsters and mice using cysteine peptidase-based vaccine","volume":"6","author":"Tallima","year":"2015","journal-title":"Front Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12399","article-title":"Papain-based vaccination modulates Schistosoma mansoni infection-induced cytokine signals","volume":"83","author":"Abdel Aziz","year":"2016","journal-title":"Scand J Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005443","article-title":"Protective immune responses against Schistosoma mansoni infection by immunization with functionally active gut-derived cysteine peptidases alone and in combination with glyceraldehyde 3-phosphate dehydrogenase","volume":"11","author":"Tallima","year":"2017","journal-title":"PloS Negl Trop Dis"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2017.10.069","article-title":"Protection against Schistosoma haematobium infection in hamsters by immunization with Schist osoma mansoni gut-derived cysteine peptidases, SmCB1 and SmCL3","volume":"35","author":"Tallima","year":"2017","journal-title":"Vaccine"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.29252\/vacres.6.2.1","article-title":"Immunogenicity and protective capacity of Schistosoma haematobium recombinant cathepsin L against infection of hamsters with","volume":"6","author":"Abdel Aziz","year":"2019","journal-title":"S Haematobium Vaccine Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007345","article-title":"A highly expressed intestinal cysteine protease of Ancylostoma ceylanicum protects vaccinated hamsters from hookworm infection","volume":"13","author":"Noon","year":"2019","journal-title":"PloS Negl Trop Dis"},{"key":"B56","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/0166-6851(80)90039-0","article-title":"The incorporation and utilization of radiolabelled lipids by adult Schistosoma mansoni in vitro","volume":"1","author":"Rumjanek","year":"1980","journal-title":"Mol Biochem Parasitol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/164_2018_179","article-title":"Exploring the therapeutic landscape of sphingomyelinases","volume":"259","author":"Shanbhogue","year":"2020","journal-title":"Handb Exp Pharmacol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/978-1-4939-9424-3_5","article-title":"A close-up view of the impact of arachidonic acid on the phagocyte NADPH oxidase","volume":"1982","author":"Bizouarn","year":"2019","journal-title":"Methods Mol Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/0891-5849(93)90143-i","article-title":"Towards the physiological function of uric acid","volume":"14","author":"Becker","year":"1993","journal-title":"Free Radic Biol Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-4758(98)01261-7","article-title":"Do antioxidants play a role in schistosome host-parasite interactions","volume":"14","author":"Loverde","year":"1998","journal-title":"Parasitol Today"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.609994\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T14:58:19Z","timestamp":1618412299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.609994\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":60,"alternative-id":["10.3389\/fimmu.2020.609994"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.609994","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,17]]},"article-number":"609994"}}