{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:42:51Z","timestamp":1787614971819,"version":"build-2736575974"},"reference-count":120,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of Shanghai","doi-asserted-by":"publisher","award":["20ZR1469300"],"award-info":[{"award-number":["20ZR1469300"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese National Natural Science Foundation","award":["31672245"],"award-info":[{"award-number":["31672245"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Schistosomiasis is a chronic helminthic disease of both humans and animals and the second most prevalent parasitic disease after malaria. Through a complex migration process, schistosome eggs trapped in the liver can lead to the formation of granulomas and subsequent schistosome-induced liver damage, which results in high mortality and morbidity. Although praziquantel can eliminate mature worms and prevent egg deposition, effective drugs to reverse schistosome-induced liver damage are scarce. High mobility group box 1 (HMGB1) is a multifunctional cytokine contributing to liver injury, inflammation, and immune responses in schistosomiasis by binding to cell-surface Toll-like receptors and receptors for advanced glycation end products. HMGB1 is increased in the serum of patients with schistosomiasis and enables hepatic stellate cells to adopt a proliferative myofibroblast-like phenotype, which is crucial to schistosome-induced granuloma formation. Inhibition of HMGB1 was found to generate protective responses against fibrotic diseases in animal models. Clinically, HMGB1 presents a potential target for treatment of the chronic sequelae of schistosomiasis. Here, the pivotal role of HMGB1 in granuloma formation and schistosome-induced liver damage, as well the potential of HMGB1 as a therapeutic target, are discussed.<\/jats:p>","DOI":"10.3390\/pathogens11030289","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T21:11:07Z","timestamp":1645737067000},"page":"289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["From Inflammation to Fibrosis: Novel Insights into the Roles of High Mobility Group Protein Box 1 in Schistosome-Induced Liver Damage"],"prefix":"10.3390","volume":"11","author":[{"given":"Haoran","family":"Zhong","sequence":"first","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gui","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Hou","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030031, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongxue","family":"Lv","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamei","family":"Jin","sequence":"additional","affiliation":[{"name":"National Reference Laboratory for Animal Schistosomiasis, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"},{"name":"Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","unstructured":"WHO (2002). TDR Strategic Direction for Research: Schistosomiasis, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"Gryseels","year":"2006","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S1473-3099(16)00175-4","article-title":"Outbreak of urogenital schistosomiasis in Corsica (France): An epidemiological case study","volume":"16","author":"Boissier","year":"2016","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/nrmicro801","article-title":"Focus: Schistosomiasis","volume":"2","author":"Chitsulo","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Nation, C.S., Da\u2019dara, A.A., Marchant, J.K., and Skelly, P.J. (2020). Schistosome migration in the definitive host. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007951"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"281","DOI":"10.4269\/ajtmh.1994.50.281","article-title":"Kinetics of egg production and egg excretion by Schistosoma mansoni and S. japonicum in mice infected with a single pair of worms","volume":"50","author":"Cheever","year":"1994","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ebiom.2016.10.024","article-title":"MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis","volume":"13","author":"He","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pt.2013.12.009","article-title":"Cellular and chemokine-mediated regulation in schistosome-induced hepatic pathology","volume":"30","author":"Chuah","year":"2014","journal-title":"Trends Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20084","DOI":"10.1073\/pnas.1106784108","article-title":"Geographical analysis of the role of water supply and sanitation in the risk of helminth infections of children in West Africa","volume":"108","author":"Barnett","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1056\/NEJMoa0800135","article-title":"A strategy to control transmission of Schistosoma japonicum in China","volume":"360","author":"Wang","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Caligiuri, A., Gentilini, A., Pastore, M., Gitto, S., and Marra, F. (2021). Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression. Cells, 10.","DOI":"10.3390\/cells10102759"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.pt.2003.09.005","article-title":"Drugs for the control of parasitic diseases: Current status and development in schistosomiasis","volume":"19","author":"Fenwick","year":"2003","journal-title":"Trends Parasitol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.pt.2015.03.009","article-title":"Knocking down schistosomes\u2014Promise for lentiviral transduction in parasites","volume":"31","author":"Hagen","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/nrrheum.2011.222","article-title":"HMGB1: A multifunctional alarmin driving autoimmune and inflammatory disease","volume":"8","author":"Harris","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"598987","DOI":"10.3389\/fcimb.2020.598987","article-title":"Functional Inhibition of Natural Killer Cells in a BALB\/c Mouse Model of Liver Fibrosis Induced by Schistosoma japonicum Infection","volume":"10","author":"Hu","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1084\/jem.192.4.565","article-title":"High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes","volume":"192","author":"Andersson","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1146\/annurev-immunol-030409-101323","article-title":"HMGB1 is a therapeutic target for sterile inflammation and infection","volume":"29","author":"Andersson","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.3389\/fimmu.2018.01979","article-title":"Emerging Role of HMGB1 in the Pathogenesis of Schistosomiasis Liver Fibrosis","volume":"9","author":"Vicentino","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108171","DOI":"10.1016\/j.exppara.2021.108171","article-title":"Sodium butyrate ameliorates Schistosoma japonicum-induced liver fibrosis by inhibiting HMGB1 expression","volume":"231","author":"Chen","year":"2021","journal-title":"Exp. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.3748\/wjg.v17.i36.4090","article-title":"Inhibition of high-mobility group box 1 expression by siRNA in rat hepatic stellate cells","volume":"17","author":"Ge","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1002\/hep.26976","article-title":"Hepatocyte-specific high-mobility group box 1 deletion worsens the injury in liver ischemia\/reperfusion: A role for intracellular high-mobility group box 1 in cellular protection","volume":"59","author":"Huang","year":"2014","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1432-1033.1973.tb03026.x","article-title":"A new group of chromatin-associated proteins with a high content of acidic and basic amino acids","volume":"38","author":"Goodwin","year":"1973","journal-title":"Eur. J. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nri1594","article-title":"High-mobility group box 1 protein (HMGB1): Nuclear weapon in the immune arsenal","volume":"5","author":"Lotze","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1189\/jlb.1212662","article-title":"The many faces of HMGB1: Molecular structure-functional activity in inflammation, apoptosis, and chemotaxis","volume":"93","author":"Yang","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.gene.2006.03.001","article-title":"Cloning the genes and DNA binding properties of High Mobility Group B1 (HMGB1) proteins from the human blood flukes Schistosoma mansoni and Schistosoma japonicum","volume":"377","author":"Rumjanek","year":"2006","journal-title":"Gene"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14998","DOI":"10.1016\/S0021-9258(18)42138-2","article-title":"Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins","volume":"267","author":"Neeper","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.tibs.2011.08.008","article-title":"RAGE: A single receptor fits multiple ligands","volume":"36","author":"Fritz","year":"2011","journal-title":"Trends Biochem. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00125-009-1458-9","article-title":"Multiple levels of regulation determine the role of the receptor for AGE (RAGE) as common soil in inflammation, immune responses and diabetes mellitus and its complications","volume":"52","author":"Bierhaus","year":"2009","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/35012626","article-title":"Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases","volume":"405","author":"Taguchi","year":"2000","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"38635","DOI":"10.1074\/jbc.M202515200","article-title":"Receptor for advanced glycation end products (RAGE) signaling induces CREB-dependent chromogranin expression during neuronal differentiation","volume":"277","author":"Huttunen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19919","DOI":"10.1074\/jbc.274.28.19919","article-title":"Receptor for advanced glycation end products (RAGE)-mediated neurite outgrowth and activation of NF-kappaB require the cytoplasmic domain of the receptor but different downstream signaling pathways","volume":"274","author":"Huttunen","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9889","DOI":"10.1016\/S0021-9258(17)36966-1","article-title":"Enhanced cellular oxidant stress by the interaction of advanced glycation end products with their receptors\/binding proteins","volume":"269","author":"Yan","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/1097-4644(20010401)81:1<102::AID-JCB1027>3.0.CO;2-Y","article-title":"Role of receptor for advanced glycation end-product (RAGE) and the JAK\/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells","volume":"81","author":"Huang","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s40001-015-0090-z","article-title":"Role of receptor for advanced glycation end products (RAGE) in liver disease","volume":"20","author":"Yamagishi","year":"2015","journal-title":"Eur. J. Med. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/j.jhep.2011.07.028","article-title":"Endogenous formation of N\u03b5-(carboxymethyl)lysine is increased in fatty livers and induces inflammatory markers in an in vitro model of hepatic steatosis","volume":"56","author":"Gaens","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/path.2065","article-title":"Disrupted galectin-3 causes non-alcoholic fatty liver disease in male mice","volume":"210","author":"Nomoto","year":"2006","journal-title":"J. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri1391","article-title":"Toll-like receptor signalling","volume":"4","author":"Akira","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"114657","DOI":"10.1016\/j.jep.2021.114657","article-title":"Daphnes Cortex and its licorice-processed products suppress inflammation via the TLR4\/NF-\u03baB\/NLRP3 signaling pathway and regulation of the metabolic profile in the treatment of rheumatoid arthritis","volume":"283","author":"Meng","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.1111\/jcmm.15027","article-title":"Staphylococcus aureus facilitates its survival in bovine macrophages by blocking autophagic flux","volume":"24","author":"Cai","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3389\/fvets.2020.00443","article-title":"Organic Selenium Ameliorates Staphylococcus aureus-Induced Mastitis in Rats by Inhibiting the Activation of NF-\u03baB and MAPK Signaling Pathways","volume":"7","author":"Liu","year":"2020","journal-title":"Front. Vet. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"105867","DOI":"10.1016\/j.phrs.2021.105867","article-title":"Liraglutide protects against lethal renal ischemia-reperfusion injury by inhibiting high-mobility group box 1 nuclear-cytoplasmic translocation and release","volume":"173","author":"Li","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.3389\/fimmu.2019.01000","article-title":"Regulation of Toll-Like Receptor (TLR) Signaling Pathway by Polyphenols in the Treatment of Age-Linked Neurodegenerative Diseases: Focus on TLR4 Signaling","volume":"10","author":"Azam","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.2147\/DDDT.S325814","article-title":"Prunella vulgaris L. Attenuates Experimental Autoimmune Thyroiditis by Inhibiting HMGB1\/TLR9 Signaling","volume":"15","author":"Guo","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.actatropica.2018.09.013","article-title":"Schistosomes, snails and climate change: Current trends and future expectations","volume":"190","author":"Stensgaard","year":"2019","journal-title":"Acta Trop."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"8850840","DOI":"10.1155\/2020\/8850840","article-title":"Prevalence of Schistosoma mansoni and S. haematobium in Snail Intermediate Hosts in Africa: A Systematic Review and Meta-analysis","volume":"2020","author":"Hailegebriel","year":"2020","journal-title":"J. Trop. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0014-4894(03)00024-9","article-title":"Schistosoma mansoni, S. haematobium, and S. japonicum: Early events associated with penetration and migration of schistosomula through human skin","volume":"102","author":"He","year":"2002","journal-title":"Exp. Parasitol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.pt.2005.03.003","article-title":"Comparison of skin invasion among three major species of Schistosoma","volume":"21","author":"He","year":"2005","journal-title":"Trends Parasitol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1017\/S0031182000000743","article-title":"Migration of the schistosomula of Schistosoma mansoni from the lungs to the hepatic portal system","volume":"80","author":"Miller","year":"1980","journal-title":"Parasitology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1017\/S0031182000051970","article-title":"Schistosoma mansoni: A histological study of migration in the laboratory mouse","volume":"79","author":"Wheater","year":"1979","journal-title":"Parasitology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"43","DOI":"10.7883\/yoken1952.8.43","article-title":"Studies on the host-parasite relationships of Schistosoma japonicum in common laboratory animals","volume":"8","author":"Ito","year":"1955","journal-title":"Jpn. J. Med. Sci. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1017\/S0031182000049829","article-title":"Attrition and temporal distribution of Schistosoma mansoni and S. haematobium schistosomula in laboratory mice","volume":"93","author":"Georgi","year":"1986","journal-title":"Parasitology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/BF00931187","article-title":"The energy metabolism of Schistosoma mansoni during its development in the hamster","volume":"75","author":"Tielens","year":"1988","journal-title":"Parasitol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"38","DOI":"10.4269\/ajtmh.1968.17.38","article-title":"A quantitative post-mortem study of Schistosomiasis mansoni in man","volume":"17","author":"Cheever","year":"1968","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/0001-706X(91)90044-K","article-title":"Relative distribution of Schistosoma japonicum eggs in the intestine of man: A subject of inconsistency","volume":"48","author":"Chen","year":"1991","journal-title":"Acta Trop."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0035-9203(53)90005-4","article-title":"I. The distribution of schistosome ova in the alimentary tract in subjects of bilharziasis","volume":"47","author":"Gelfand","year":"1953","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_57","first-page":"1092","article-title":"The distribution of Schistosoma eggs in human tissues","volume":"18","author":"Alves","year":"1958","journal-title":"Bull. World Health Organ."},{"key":"ref_58","first-page":"438","article-title":"Schistosomiasis of the ovary with endometriosis and corpus hemorrhagicum: A case report","volume":"23","author":"Lee","year":"2000","journal-title":"Chang. Gung Med. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1001\/jama.1964.03060330027006","article-title":"Schistosomiasis japonica involvement of the female genital tract","volume":"188","author":"Carpenter","year":"1964","journal-title":"Jama"},{"key":"ref_60","first-page":"568","article-title":"Prostatic Schistosoma japonicum with atypical immunophenotyping of individual glandular tubes: A case report and review of the literature","volume":"44","author":"Yu","year":"2013","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/jpids\/piz009","article-title":"Pediatric Neuroschistosomiasis: A Case Report and Review of the Literature","volume":"8","author":"Wen","year":"2019","journal-title":"J. Pediatric Infect. Dis. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1007\/s00381-021-05267-9","article-title":"Medullary neuroschistosomiasis in adolescence: Case report and literature review","volume":"37","author":"Dastoli","year":"2021","journal-title":"Child\u2019s Nerv. Syst."},{"key":"ref_63","first-page":"153","article-title":"Cloning and function analysis of high mobility group box 1 (HMGB1) protein of Schistosoma japonicum (Mainland strain)","volume":"26","author":"Yao","year":"2014","journal-title":"Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/0035-9203(53)90006-6","article-title":"II. The distribution of schistosome ova in the genito-urinary tract in subjects of bilharziasis","volume":"47","author":"Gelfand","year":"1953","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"846","DOI":"10.4269\/ajtmh.1971.20.846","article-title":"Distribution and extent of schistosomiasis in female pelvic organs, with special reference to the genital tract, as determined at autopsy","volume":"20","author":"Gelfand","year":"1971","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"779","DOI":"10.4269\/ajtmh.1970.19.779","article-title":"Schistosomiasis of the male pelvic organs. Severity of infection as determined by digestion of tissue and histologic methods in 300 cadavers","volume":"19","author":"Gelfand","year":"1970","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1111\/j.1365-3024.2009.01157.x","article-title":"Schistosomiasis and liver fibrosis","volume":"31","author":"Andrade","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1017\/S0031182001007351","article-title":"The schistosome egg: Development and secretions","volume":"122","author":"Ashton","year":"2001","journal-title":"Parasitology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/infdis\/jiq099","article-title":"Tissue inhibitor of matrix-metalloprotease-1 predicts risk of hepatic fibrosis in human Schistosoma japonicum infection","volume":"203","author":"Fabre","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1086\/510313","article-title":"Th2 cytokines are associated with persistent hepatic fibrosis in human Schistosoma japonicum infection","volume":"195","author":"Coutinho","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.pt.2018.02.005","article-title":"Schistosome-Induced Fibrotic Disease: The Role of Hepatic Stellate Cells","volume":"34","author":"Carson","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/sj.icb.7100014","article-title":"Immunopathology of schistosomiasis","volume":"85","author":"Wilson","year":"2007","journal-title":"Immunol. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"777","DOI":"10.4049\/jimmunol.159.2.777","article-title":"IL-4 protects against TNF-alpha-mediated cachexia and death during acute schistosomiasis","volume":"159","author":"Brunet","year":"1997","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"292","DOI":"10.4269\/ajtmh.1970.19.292","article-title":"Granuloma formation around Schistosoma mansoni, S. haematobium, and S. japonicum eggs. Size and rate of development, cellular composition, cross-sensitivity, and rate of egg destruction","volume":"19","author":"Warren","year":"1970","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.molbiopara.2006.01.003","article-title":"IPSE\/alpha-1: A major immunogenic component secreted from Schistosoma mansoni eggs","volume":"147","author":"Schramm","year":"2006","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"18384","DOI":"10.1074\/jbc.M300497200","article-title":"Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs","volume":"278","author":"Schramm","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1189\/jlb.1212653","article-title":"Spatial and temporal transcriptomics of Schistosoma japonicum-induced hepatic granuloma formation reveals novel roles for neutrophils","volume":"94","author":"Chuah","year":"2013","journal-title":"J. Leukoc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1053\/hupa.2000.8440","article-title":"Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver","volume":"31","author":"Washington","year":"2000","journal-title":"Hum. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"674","DOI":"10.4321\/S1130-01082006000900005","article-title":"Hepatic stellate cells and alcoholic liver disease","volume":"98","author":"Vera","year":"2006","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.ijpara.2006.04.015","article-title":"A contributory role for activated hepatic stellate cells in the dynamics of Schistosoma japonicum egg-induced fibrosis","volume":"36","author":"Bartley","year":"2006","journal-title":"Int. J. Parasitol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-beta\/SMAD Pathway and Its Regulation in Hepatic Fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Alisi, A., He, X., Pu, G., Tang, R., Zhang, D., and Pan, W. (2014). Activation of Nuclear Factor Kappa B in the Hepatic Stellate Cells of Mice with Schistosomiasis Japonica. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104323"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.4049\/jimmunol.142.9.3239","article-title":"Characterization of granuloma T lymphocyte function from Schistosoma mansoni-infected mice","volume":"142","author":"Ragheb","year":"1989","journal-title":"J. Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/cimm.2000.1687","article-title":"Influence of alternatively and classically activated macrophages on fibrogenic activities of human fibroblasts","volume":"204","author":"Song","year":"2000","journal-title":"Cell. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1517\/14728222.12.2.145","article-title":"Targeting neutrophil elastase in cystic fibrosis","volume":"12","author":"Kelly","year":"2008","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"172487","DOI":"10.1016\/j.ejphar.2019.172487","article-title":"Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: Updates on receptor signalling","volume":"858","author":"Paudel","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.bbi.2016.09.017","article-title":"Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1","volume":"59","author":"Lian","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"13431","DOI":"10.1002\/jcp.28022","article-title":"Inhibition of HMGB1 improves necrotizing enterocolitis by inhibiting NLRP3 via TLR4 and NF-kappaB signaling pathways","volume":"234","author":"Yu","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1053\/jhep.2001.25350","article-title":"Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice","volume":"34","author":"Uesugi","year":"2001","journal-title":"Hepatology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7269","DOI":"10.1128\/JVI.79.11.7269-7272.2005","article-title":"Toll-like receptor signaling inhibits hepatitis B virus replication in vivo","volume":"79","author":"Isogawa","year":"2005","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.lfs.2017.04.025","article-title":"Toll like receptor 4 and hepatocellular carcinoma; A systematic review","volume":"179","author":"Sepehri","year":"2017","journal-title":"Life Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-beta signaling and hepatic fibrosis","volume":"13","author":"Seki","year":"2007","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1146\/annurev.immunol.021908.132641","article-title":"Regulation and function of NF-kappaB transcription factors in the immune system","volume":"27","author":"Vallabhapurapu","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1080\/21691401.2019.1671433","article-title":"Taraxasterol from Taraxacum prevents concanavalin A-induced acute hepatic injury in mice via modulating TLRs\/NF-\u03baB and Bax\/Bc1-2 signalling pathways","volume":"47","author":"Sang","year":"2019","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00210-018-1560-y","article-title":"Targeting HMGB1\/TLR4 axis and miR-21 by rosuvastatin: Role in alleviating cholestatic liver injury in a rat model of bile duct ligation","volume":"392","author":"Nabih","year":"2019","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1002\/hep.28948","article-title":"The origin of fibrogenic myofibroblasts in fibrotic liver","volume":"65","author":"Kisseleva","year":"2017","journal-title":"Hepatology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1972746","DOI":"10.1080\/19490976.2021.1972746","article-title":"Ursolic acid reverses liver fibrosis by inhibiting NOX4\/NLRP3 inflammasome pathways and bacterial dysbiosis","volume":"13","author":"Nie","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1785738","DOI":"10.1080\/20013078.2020.1785738","article-title":"Sja-miR-71a in Schistosome egg-derived extracellular vesicles suppresses liver fibrosis caused by schistosomiasis via targeting semaphorin 4D","volume":"9","author":"Wang","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3389\/fimmu.2012.00116","article-title":"IL-13 Signaling in Liver Fibrogenesis","volume":"3","author":"Liu","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1146\/annurev-pathol-011110-130246","article-title":"Pathogenesis of liver fibrosis","volume":"6","author":"Friedman","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Khambu, B., Yan, S., Huda, N., and Yin, X.M. (2019). Role of High-Mobility Group Box-1 in Liver Pathogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215314"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1111\/jcmm.12419","article-title":"Emerging role of HMGB1 in fibrotic diseases","volume":"18","author":"Li","year":"2014","journal-title":"J. Cell. Mol. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1016\/j.bbadis.2014.06.017","article-title":"Involvement of the nuclear high mobility group B1 peptides released from injured hepatocytes in murine hepatic fibrogenesis","volume":"1842","author":"Kao","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1089\/vim.2010.0080","article-title":"Is HMGB1 a new indirect marker for revealing fibrosis in chronic hepatitis and a new therapeutic target in treatment?","volume":"23","author":"Albayrak","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_105","first-page":"1960","article-title":"Transforming growth factor-\u03b21 induced epithelial-mesenchymal transition in hepatic fibrosis","volume":"59","author":"Bi","year":"2012","journal-title":"Hepato-Gastroenterology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1053\/jhep.2001.25349","article-title":"The role of Smad3 in mediating mouse hepatic stellate cell activation","volume":"34","author":"Schnabl","year":"2001","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Itatani, Y., Kawada, K., and Sakai, Y. (2019). Transforming Growth Factor-beta Signaling Pathway in Colorectal Cancer and Its Tumor Microenvironment. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235822"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1146\/annurev.biochem.67.1.753","article-title":"TGF-beta signal transduction","volume":"67","year":"1998","journal-title":"Annu. Rev. biochem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"BSR20203131","DOI":"10.1042\/BSR20203131","article-title":"MiR-92d-3p suppresses the progression of diabetic nephropathy renal fibrosis by inhibiting the C3\/HMGB1\/TGF-\u03b21 pathway","volume":"41","author":"Zhang","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"115757","DOI":"10.1016\/j.taap.2021.115757","article-title":"Arsenic-induced lung inflammation and fibrosis in a rat model: Contribution of the HMGB1\/RAGE, PI3K\/AKT, and TGF-\u03b21\/SMAD pathways","volume":"432","author":"Wang","year":"2021","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1136\/gutjnl-2015-310752","article-title":"Signalling via the osteopontin and high mobility group box-1 axis drives the fibrogenic response to liver injury","volume":"66","author":"Arriazu","year":"2017","journal-title":"Gut"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1002\/hep.30093","article-title":"High Mobility Group Box-1 Drives Fibrosis Progression Signaling via the Receptor for Advanced Glycation End Products in Mice","volume":"68","author":"Ge","year":"2018","journal-title":"Hepatology"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Wyganowska-Swiatkowska, M., Nohawica, M., Grocholewicz, K., and Nowak, G. (2020). Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134639"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cell.2020.10.028","article-title":"Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection","volume":"184","author":"Wei","year":"2021","journal-title":"Cell"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2722","DOI":"10.1096\/fj.201700875R","article-title":"Dual regulation of HMGB1 by combined JNK1\/2-ATF2 axis with miR-200 family in nonalcoholic steatohepatitis in mice","volume":"32","author":"Chen","year":"2018","journal-title":"FASEB J."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"477","DOI":"10.2119\/molmed.2012.00024","article-title":"Inhibition of high-mobility group box 1 protein (HMGB1) enhances bacterial clearance and protects against Pseudomonas Aeruginosa pneumonia in cystic fibrosis","volume":"18","author":"Entezari","year":"2012","journal-title":"Mol. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S1386-6346(00)00079-6","article-title":"Therapeutic effects of stronger neo-minophagen C at different doses on chronic hepatitis and liver cirrhosis","volume":"19","author":"Iino","year":"2001","journal-title":"Hepatol. Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1124\/jpet.111.182592","article-title":"Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion in rats","volume":"339","author":"Ogiku","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"679","DOI":"10.3748\/wjg.v18.i7.679","article-title":"Glycyrrhizin attenuates HMGB1-induced hepatocyte apoptosis by inhibiting the p38-dependent mitochondrial pathway","volume":"18","author":"Gwak","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"155496","DOI":"10.1016\/j.cyto.2021.155496","article-title":"Glycyrrhizin prevents SARS-CoV-2 S1 and Orf3a induced high mobility group box 1 (HMGB1) release and inhibits viral replication","volume":"142","author":"Gowda","year":"2021","journal-title":"Cytokine"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/3\/289\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:26:42Z","timestamp":1760135202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/3\/289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":120,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["pathogens11030289"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11030289","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]}}}