{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T03:40:36Z","timestamp":1792554036628,"version":"4.5.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Schistosomiasis drastically affects human health, where <jats:italic>S. mansoni<\/jats:italic>-induced hepatic fibrosis remains a serious problem with no available drug yet. The current study aimed to evaluate the hepatoprotective effects of Vildagliptin (Vilda), Diaminodiphenyl Sulfone (DDS), and their combination (Vilda\/DDS) against <jats:italic>S. mansoni<\/jats:italic>-induced hepatic fibrosis and elucidate their underlying molecular mechanisms. <jats:italic>S.mansoni<\/jats:italic>-infected mice were administered praziquantel (PZQ) for two consecutive days, or Vilda, DDS, and Vilda\/DDS for 14 consecutive days. Schistosomiasis-induced hepatic fibrosis was assessed parasitologically, biochemically, and pathologically. Results revealed that Vilda, DDS, and Vida\/DDS treatments significantly reduced worm count, oogram stages, ova count, and ameliorated the granulomatous inflammatory reactions and hepatotoxicity indices. Moreover, they enhanced hepatic Nrf2\/HO-1 pathway with significant increasing SOD and reducing MDA levels. Furthermore, they significantly downregulated the hepatic TLR4\/NF-\u03baB and NLRP3 inflammasome pathways leading to a significant reduction in TNF-\u03b1 and caspase-1 levels which is important in the activation of IL-1\u03b2 and caspase-3. Notably, significant downregulation in hepatic TGF-\u03b21, \u03b1-SMA, and MMP-9 expressions were also recorded. In conclusion, Vilda\/DDS showed antioxidant, anti-inflammatory and antifibrotic activities in comparison to either Vilda or DDS alone against <jats:italic>S. mansoni<\/jats:italic>-induced hepatic fibrosis. Therefore, Vilda\/DDS is a promising approach for managing <jats:italic>S. mansoni<\/jats:italic> infection, liver fibrosis, and associated disease morbidity.<\/jats:p>","DOI":"10.1038\/s41598-025-91955-4","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T12:28:33Z","timestamp":1742819313000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The antifibrotic effect of Vildagliptin and Diaminodiphenyl Sulfone in murine schistosomiasis mansoni"],"prefix":"10.1038","volume":"15","author":[{"given":"Amira S.","family":"Hendawy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Nasser A.","family":"Sabra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina Y.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman","family":"Rashad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebtehal","family":"El-Demerdash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanaa S.","family":"Botros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"91955_CR1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/tropicalmed5010020","volume":"5","author":"DW Gunda","year":"2020","unstructured":"Gunda, D. W., Kilonzo, S. B., Manyiri, P. M., Peck, R. N. & Mazigo, H. D. Morbidity and mortality due to Schistosoma mansoni related periportal fibrosis: Could early diagnosis of varices improve the outcome following available treatment modalities in Sub Saharan Africa? A scoping review. Trop. Med. Infect. Dis. 5, 20 (2020).","journal-title":"Trop. Med. Infect. Dis."},{"key":"91955_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02265","author":"JL Wilson","year":"2019","unstructured":"Wilson, J. L., Mayr, H. K. & Weichhart, T. Metabolic programming of macrophages: Implications in the pathogenesis of granulomatous disease. Front. Immunol. https:\/\/doi.org\/10.3389\/fimmu.2019.02265 (2019).","journal-title":"Front. Immunol."},{"key":"91955_CR3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/S1473-3099(21)00090-6","volume":"22","author":"C Kokaliaris","year":"2022","unstructured":"Kokaliaris, C. et al. Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: A spatiotemporal modelling study. Lancet Infect. Dis. 22, 136\u2013149 (2022).","journal-title":"Lancet Infect. Dis."},{"key":"91955_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-023-47646-z","volume":"13","author":"L H\u00e4rle","year":"2023","unstructured":"H\u00e4rle, L. et al. Hepatocyte integrity depends on c-Jun-controlled proliferation in Schistosoma mansoni infected mice. Sci. Rep. 13, 1\u201313 (2023).","journal-title":"Sci. Rep."},{"key":"91955_CR5","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.bjid.2014.11.004","volume":"19","author":"AF Adenowo","year":"2015","unstructured":"Adenowo, A. F., Oyinloye, B. E., Ogunyinka, B. I. & Kappo, A. P. Impact of human schistosomiasis in sub-Saharan Africa. Braz. J. Infect. Dis. 19, 196\u2013205 (2015).","journal-title":"Braz. J. Infect. Dis."},{"key":"91955_CR6","unstructured":"Shawn Horrall, E. K. L. (2023). Schistosomiasis - PubMed. https:\/\/pubmed.ncbi.nlm.nih.gov\/32119321\/ (2023)."},{"key":"91955_CR7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/0163-7258(95)00026-7","volume":"68","author":"D Cioli","year":"1995","unstructured":"Cioli, D., Pica-Mattoccia, L. & Archer, S. Antischistosomal drugs: Past, present \u2026 and future?. Pharmacol. Ther. 68, 35\u201385 (1995).","journal-title":"Pharmacol. Ther."},{"key":"91955_CR8","doi-asserted-by":"publisher","first-page":"e20247","DOI":"10.1371\/journal.pone.0020247","volume":"6","author":"YJ Liang","year":"2011","unstructured":"Liang, Y. J. et al. New Insight into the Antifibrotic Effects of Praziquantel on Mice in Infection with Schistosoma japonicum. PLoS One 6, e20247 (2011).","journal-title":"PLoS One"},{"key":"91955_CR9","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67514-4","author":"JK Nono","year":"2020","unstructured":"Nono, J. K. et al. Investigating the antifibrotic effect of the antiparasitic drug Praziquantel in in vitro and in vivo preclinical models. Sci. Rep. https:\/\/doi.org\/10.1038\/s41598-020-67514-4 (2020).","journal-title":"Sci. Rep."},{"key":"91955_CR10","doi-asserted-by":"publisher","first-page":"116881","DOI":"10.1016\/j.lfs.2019.116881","volume":"239","author":"C Wu","year":"2019","unstructured":"Wu, C. et al. Salvianolic acid B exerts anti-liver fibrosis effects via inhibition of MAPK-mediated phospho-Smad2\/3 at linker regions in vivo and in vitro. Life Sci. 239, 116881 (2019).","journal-title":"Life Sci."},{"key":"91955_CR11","doi-asserted-by":"crossref","unstructured":"Costain, A. H., MacDonald, A. S. & Smits, H. H. Schistosome egg migration: Mechanisms, pathogenesis and host immune responses. Front. Immunol. 9, (2018).","DOI":"10.3389\/fimmu.2018.03042"},{"key":"91955_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/antiox10010088","volume":"10","author":"AI Mazur-Bialy","year":"2021","unstructured":"Mazur-Bialy, A. I. & Poche\u0107, E. The time-course of antioxidant Irisin activity: Role of the Nrf2\/HO-1\/HMGB1 axis. Antioxidants 10, 1\u201313 (2021).","journal-title":"Antioxidants"},{"key":"91955_CR13","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/S0076-6879(10)80006-0","volume":"480","author":"I van Die","year":"2010","unstructured":"van Die, I., van Stijn, C. M. W., Geyer, H. & Geyer, R. Structural and functional analysis of glycosphingolipids of Schistosoma mansoni. Methods Enzymol. 480, 117\u2013140 (2010).","journal-title":"Methods Enzymol."},{"key":"91955_CR14","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.celrep.2013.12.014","volume":"6","author":"P Kalantari","year":"2014","unstructured":"Kalantari, P. et al. Dual engagement of the NLRP3 and AIM2 inflammasomes by plasmodium-derived hemozoin and DNA during malaria. Cell Rep. 6, 196\u2013210 (2014).","journal-title":"Cell Rep."},{"key":"91955_CR15","first-page":"526840","volume":"11","author":"J Yang","year":"2020","unstructured":"Yang, J., Wise, L. & Fukuchi, K. I. TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer\u2019s disease. Front. Immunol. 11, 526840 (2020).","journal-title":"Front. Immunol."},{"key":"91955_CR16","doi-asserted-by":"publisher","first-page":"3720","DOI":"10.1182\/blood-2010-07-273417","volume":"117","author":"CA Dinarello","year":"2011","unstructured":"Dinarello, C. A. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117, 3720\u20133732 (2011).","journal-title":"Blood"},{"key":"91955_CR17","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1007\/s10620-017-4609-8","volume":"62","author":"LD Lazaridis","year":"2017","unstructured":"Lazaridis, L. D. et al. Activation of NLRP3 inflammasome in inflammatory bowel disease: Differences between Crohn\u2019s disease and ulcerative colitis. Dig. Dis. Sci. 62, 2348\u20132356 (2017).","journal-title":"Dig. Dis. Sci."},{"key":"91955_CR18","doi-asserted-by":"publisher","first-page":"699","DOI":"10.5009\/gnl15430","volume":"9","author":"T Il Kim","year":"2015","unstructured":"Il Kim, T. The role of barrier dysfunction and change of Claudin expression in inflammatory bowel disease. Gut Liver 9, 699 (2015).","journal-title":"Gut Liver"},{"key":"91955_CR19","doi-asserted-by":"publisher","DOI":"10.1111\/pim.12592","author":"M Egesa","year":"2018","unstructured":"Egesa, M. et al. Schistosoma mansoni schistosomula antigens induce Th1\/Pro-inflammatory cytokine responses. Parasite Immunol. https:\/\/doi.org\/10.1111\/pim.12592 (2018).","journal-title":"Parasite Immunol."},{"key":"91955_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13071-015-0640-9","volume":"8","author":"D Zhu","year":"2015","unstructured":"Zhu, D. et al. Expression of Septin4 in Schistosoma japonicum-infected mouse livers after praziquantel treatment. Parasit. Vectors 8, 1\u20137 (2015).","journal-title":"Parasit. Vectors"},{"key":"91955_CR21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/s00441-011-1246-y","volume":"347","author":"S Dooley","year":"2012","unstructured":"Dooley, S. & Ten Dijke, P. TGF-\u03b2 in progression of liver disease. Cell Tissue Res. 347, 245\u2013256 (2012).","journal-title":"Cell Tissue Res."},{"key":"91955_CR22","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1002\/cphy.c120020","volume":"3","author":"ME Guicciardi","year":"2013","unstructured":"Guicciardi, M. E., Malhi, H., Mott, J. L. & Gores, G. J. Apoptosis and necrosis in the liver. Compr. Physiol. 3, 977\u20131010 (2013).","journal-title":"Compr. Physiol."},{"key":"91955_CR23","doi-asserted-by":"publisher","first-page":"e18861","DOI":"10.1590\/s2175-979020200003180861","volume":"56","author":"A Alm-Eldeen","year":"2021","unstructured":"Alm-Eldeen, A., Khamis, A., Elfiky, N. & Ahmad, R. Quercetin modulates age-induced changes in the transcript levels of some apoptosis related genes in the skeletal muscles of male rats. Braz. J. Pharm. Sci. 56, e18861 (2021).","journal-title":"Braz. J. Pharm. Sci."},{"key":"91955_CR24","doi-asserted-by":"publisher","first-page":"399","DOI":"10.5501\/wjv.v11.i6.399","volume":"11","author":"N Narayanan","year":"2022","unstructured":"Narayanan, N., Naik, D., Sahoo, J. & Kamalanathan, S. Dipeptidyl peptidase 4 inhibitors in COVID-19: Beyond glycemic control. World J. Virol. 11, 399 (2022).","journal-title":"World J. Virol."},{"key":"91955_CR25","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1016\/j.jhep.2010.09.032","volume":"54","author":"S Ben-Shlomo","year":"2011","unstructured":"Ben-Shlomo, S. et al. Glucagon-like peptide-1 reduces hepatic lipogenesis via activation of AMP-activated protein kinase. J. Hepatol. 54, 1214\u20131223 (2011).","journal-title":"J. Hepatol."},{"key":"91955_CR26","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s00535-013-0783-4","volume":"49","author":"K Kaji","year":"2014","unstructured":"Kaji, K. et al. Dipeptidyl peptidase-4 inhibitor attenuates hepatic fibrosis via suppression of activated hepatic stellate cell in rats. J. Gastroenterol. 49, 481\u2013491 (2014).","journal-title":"J. Gastroenterol."},{"key":"91955_CR27","doi-asserted-by":"publisher","first-page":"120695","DOI":"10.1016\/j.lfs.2022.120695","volume":"304","author":"AS Hendawy","year":"2022","unstructured":"Hendawy, A. S. et al. Vildagliptin alleviates liver fibrosis in NASH diabetic rats via modulation of insulin resistance, oxidative stress, and inflammatory cascades. Life Sci. 304, 120695 (2022).","journal-title":"Life Sci."},{"key":"91955_CR28","first-page":"101957","volume":"32","author":"A Matsumoto","year":"2023","unstructured":"Matsumoto, A., Fukuoka, H., Yoneda, A., Yokoi, N. & Sotozono, C. Effect of metformin combined with DPP-4 inhibitor on alveolar bone density in patients with type 2 diabetes mellitus and chronic periodontitis. Shanghai Kou Qiang Yi Xue 32, 101957 (2023).","journal-title":"Shanghai Kou Qiang Yi Xue"},{"key":"91955_CR29","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1067\/mjd.2001.114733","volume":"45","author":"YI Zhu","year":"2001","unstructured":"Zhu, Y. I. & Stiller, M. J. Dapsone and sulfones in dermatology: Overview and update. J. Am. Acad. Dermatol. 45, 420\u2013434 (2001).","journal-title":"J. Am. Acad. Dermatol."},{"key":"91955_CR30","first-page":"1","volume":"21","author":"JH Lee","year":"2020","unstructured":"Lee, J. H., An, H. K., Sohn, M. G., Kivela, P. & Oh, S. 4,4\u2032-diaminodiphenyl sulfone (DDS) as an inflammasome competitor. Int. J. Mol. Sci. 21, 1\u201323 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"91955_CR31","doi-asserted-by":"publisher","first-page":"4817","DOI":"10.3390\/molecules26164817","volume":"26","author":"HRM Rashdan","year":"2021","unstructured":"Rashdan, H. R. M., Shehadi, I. A., Abdelrahman, M. T. & Hemdan, B. A. Antibacterial activities and molecular docking of novel sulfone biscompound containing bioactive 1,2,3-triazole moiety. Molecules 26, 4817 (2021).","journal-title":"Molecules"},{"key":"91955_CR32","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1007\/s00210-022-02297-1","volume":"395","author":"M Khalilzadeh","year":"2022","unstructured":"Khalilzadeh, M. et al. A comprehensive insight into the anti-inflammatory properties of dapsone. Naunyn Schmiedebergs Arch. Pharmacol. 395, 1509\u20131523 (2022).","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"91955_CR33","doi-asserted-by":"publisher","first-page":"e1903","DOI":"10.1371\/journal.pntd.0001903","volume":"6","author":"X Wang","year":"2012","unstructured":"Wang, X. et al. Projecting the long-term impact of school- or community-based mass-treatment interventions for control of schistosoma infection. PLoS Negl. Trop. Dis. 6, e1903 (2012).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"91955_CR34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/ph11010015","volume":"11","author":"MJ Gouveia","year":"2018","unstructured":"Gouveia, M. J., Brindley, P. J., G\u00e4rtner, F., Correia Da Costa, J. M. & Vale, N. Drug repurposing for schistosomiasis: Combinations of drugs or biomolecules. Pharmaceuticals 11, 15 (2018).","journal-title":"Pharmaceuticals"},{"key":"91955_CR35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.molbiopara.2014.06.002","volume":"195","author":"D Cioli","year":"2014","unstructured":"Cioli, D., Pica-Mattoccia, L., Basso, A. & Guidi, A. Schistosomiasis control: Praziquantel forever?. Mol. Biochem. Parasitol. 195, 23\u201329 (2014).","journal-title":"Mol. Biochem. Parasitol."},{"key":"91955_CR36","doi-asserted-by":"crossref","unstructured":"Vale, N. et al. Praziquantel for schistosomiasis: Single-drug metabolism revisited, mode of action, and resistance. Antimicrob. Agents Chemother. 61, (2017).","DOI":"10.1128\/AAC.02582-16"},{"key":"91955_CR37","doi-asserted-by":"crossref","unstructured":"Guerra, R. A. et al. In vitro and in vivo studies of spironolactone as an antischistosomal drug capable of clinical repurposing. Antimicrob. Agents Chemother. 63, (2019).","DOI":"10.1128\/AAC.01722-18"},{"key":"91955_CR38","unstructured":"World Health Organization. WHO guideline on control and elimination of human schistosomiasis. 118."},{"key":"91955_CR39","doi-asserted-by":"crossref","unstructured":"Abbruzzese, C. et al. Drug repurposing for the treatment of glioblastoma multiforme. J. Exp. Clin. Cancer Res. 36, (2017).","DOI":"10.1186\/s13046-017-0642-x"},{"key":"91955_CR40","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1038\/nrd1468","volume":"3","author":"TT Ashburn","year":"2004","unstructured":"Ashburn, T. T. & Thor, K. B. Drug repositioning: Identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov. 3, 673\u2013683 (2004).","journal-title":"Nat. Rev. Drug Discov."},{"key":"91955_CR41","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ebiom.2019.04.029","volume":"43","author":"EM Lago","year":"2019","unstructured":"Lago, E. M. et al. Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis. EBioMedicine 43, 370\u2013379 (2019).","journal-title":"EBioMedicine"},{"key":"91955_CR42","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/s00436-011-2267-x","volume":"109","author":"OMS Mostafa","year":"2011","unstructured":"Mostafa, O. M. S., Eid, R. A. & Adly, M. A. Antischistosomal activity of ginger (Zingiber officinale) against Schistosoma mansoni harbored in C57 mice. Parasitol. Res. 109, 395\u2013403 (2011).","journal-title":"Parasitol. Res."},{"key":"91955_CR43","doi-asserted-by":"publisher","first-page":"201","DOI":"10.4269\/ajtmh.1962.11.201","volume":"11","author":"J Pellegrino","year":"1962","unstructured":"Pellegrino, J., Oliveira, C. A., Faria, J. & Cunha, A. S. New approach to the screening of drugs in experimental schistosomiasis Mansoni in mice. Am. J. Trop. Med. Hyg. 11, 201\u2013215 (1962).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"91955_CR44","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.jmii.2021.03.017","volume":"55","author":"HYP Lam","year":"2022","unstructured":"Lam, H. Y. P. et al. Antifibrotic and anthelminthic effect of casticin on Schistosoma mansoni-infected BALB\/c mice. J. Microbiol. Immunol. Infect. 55, 314\u2013322 (2022).","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"91955_CR45","doi-asserted-by":"publisher","first-page":"4542","DOI":"10.3390\/molecules26154542","volume":"26","author":"AH Abu Almaaty","year":"2021","unstructured":"Abu Almaaty, A. H. et al. Parasitological and biochemical efficacy of the active ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni infected mice. Molecules 26, 4542 (2021).","journal-title":"Molecules"},{"key":"91955_CR46","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-5-9","author":"NM El-Lakkany","year":"2012","unstructured":"El-Lakkany, N. M. et al. Anti-inflammatory\/anti-fibrotic effects of the hepatoprotective silymarin and the schistosomicide praziquantel against Schistosoma mansoni-induced liver fibrosis. Parasit. Vectors https:\/\/doi.org\/10.1186\/1756-3305-5-9 (2012).","journal-title":"Parasit. Vectors"},{"key":"91955_CR47","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.3892\/mmr.2015.4690","volume":"13","author":"Z Liu","year":"2016","unstructured":"Liu, Z. et al. Curcumin upregulates Nrf2 nuclear translocation and protects rat hepatic stellate cells against oxidative stress. Mol. Med. Rep. 13, 1717\u20131724 (2016).","journal-title":"Mol. Med. Rep."},{"key":"91955_CR48","first-page":"223","volume":"99","author":"R Urtasun","year":"2007","unstructured":"Urtasun, R. & Nieto, N. Hepatic stellate cells and oxidative stress. Revista espanola de enfermedades digestivas 99, 223\u2013230 (2007).","journal-title":"Revista espanola de enfermedades digestivas"},{"key":"91955_CR49","doi-asserted-by":"publisher","first-page":"e0204923","DOI":"10.1371\/journal.pone.0204923","volume":"13","author":"RS Almeer","year":"2018","unstructured":"Almeer, R. S., El-Khadragy, M. F., Abdelhabib, S. & Moneim, A. E. A. Ziziphus spina-christi leaf extract ameliorates schistosomiasis liver granuloma, fibrosis, and oxidative stress through downregulation of fibrinogenic signaling in mice. PLoS One 13, e0204923 (2018).","journal-title":"PLoS One"},{"key":"91955_CR50","doi-asserted-by":"publisher","first-page":"16023","DOI":"10.1074\/jbc.275.21.16023","volume":"275","author":"T Ishii","year":"2000","unstructured":"Ishii, T. et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J. Biol. Chem. 275, 16023\u201316029 (2000).","journal-title":"J. Biol. Chem."},{"key":"91955_CR51","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.arcmed.2013.03.004","volume":"44","author":"DL \u00c1vila","year":"2013","unstructured":"\u00c1vila, D. L. et al. Vildagliptin ameliorates oxidative stress and pancreatic beta cell destruction in type 1 diabetic rats. Arch. Med. Res. 44, 194\u2013202 (2013).","journal-title":"Arch. Med. Res."},{"key":"91955_CR52","doi-asserted-by":"publisher","first-page":"1819","DOI":"10.1007\/s11064-013-1087-z","volume":"38","author":"A Diaz-Ruiz","year":"2013","unstructured":"Diaz-Ruiz, A. et al. Antioxidant, anticonvulsive and neuroprotective effects of dapsone and phenobarbital against kainic acid-induced damage in rats. Neurochem. Res. 38, 1819\u20131827 (2013).","journal-title":"Neurochem. Res."},{"key":"91955_CR53","doi-asserted-by":"publisher","DOI":"10.1017\/S0022149X19000622","author":"TTW Chen","year":"2019","unstructured":"Chen, T. T. W. et al. Activation of the NLRP3 and AIM2 inflammasomes in a mouse model of Schistosoma mansoni infection. J. Helminthol. https:\/\/doi.org\/10.1017\/S0022149X19000622 (2019).","journal-title":"J. Helminthol."},{"key":"91955_CR54","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.gendis.2021.12.006","volume":"10","author":"HV Charan","year":"2023","unstructured":"Charan, H. V., Dwivedi, D. K., Khan, S. & Jena, G. Mechanisms of NLRP3 inflammasome-mediated hepatic stellate cell activation: Therapeutic potential for liver fibrosis. Genes Dis. 10, 480\u2013494 (2023).","journal-title":"Genes Dis."},{"key":"91955_CR55","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01735-2","author":"C Liu","year":"2020","unstructured":"Liu, C. et al. Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-\u03b3-activated MSC through modulating Th1\/Th2 responses. Stem Cell Res. Ther. https:\/\/doi.org\/10.1186\/s13287-020-01735-2 (2020).","journal-title":"Stem Cell Res. Ther."},{"key":"91955_CR56","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1040270","author":"N Dibo","year":"2022","unstructured":"Dibo, N., Liu, X., Chang, Y., Huang, S. & Wu, X. Pattern recognition receptor signaling and innate immune responses to schistosome infection. Front. Cell. Infect. Microbiol. https:\/\/doi.org\/10.3389\/fcimb.2022.1040270 (2022).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"91955_CR57","doi-asserted-by":"publisher","DOI":"10.1093\/pnasnexus\/pgae104","author":"P Ghezellou","year":"2024","unstructured":"Ghezellou, P. et al. Schistosoma mansoni infection induces hepatic metallothionein and S100 protein expression alongside metabolic dysfunction in hamsters. PNAS Nexus https:\/\/doi.org\/10.1093\/pnasnexus\/pgae104 (2024).","journal-title":"PNAS Nexus"},{"key":"91955_CR58","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1097\/00007890-199907150-00018","volume":"68","author":"S Natori","year":"1999","unstructured":"Natori, S. et al. Apoptosis of sinusoidal endothelial cells occurs during liver preservation injury by a caspase-dependent mechanism. Transplantation 68, 89\u201396 (1999).","journal-title":"Transplantation"},{"key":"91955_CR59","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.actatropica.2015.04.004","volume":"148","author":"TTW Chen","year":"2015","unstructured":"Chen, T. T. W. et al. Mitochondrial dynamics in the mouse liver infected by Schistosoma mansoni. Acta Trop. 148, 13\u201323 (2015).","journal-title":"Acta Trop."},{"key":"91955_CR60","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3509091","author":"IO Sherif","year":"2018","unstructured":"Sherif, I. O. & Al-Shaalan, N. H. Vildagliptin attenuates hepatic ischemia\/reperfusion injury via the TLR4\/NF-\u03baB signaling pathway. Oxid. Med. Cell Longev. https:\/\/doi.org\/10.1155\/2018\/3509091 (2018).","journal-title":"Oxid. Med. Cell Longev."},{"key":"91955_CR61","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.1111\/febs.13665","volume":"283","author":"I Fabregat","year":"2016","unstructured":"Fabregat, I. et al. TGF-\u03b2 signalling and liver disease. FEBS J. 283, 2219\u20132232 (2016).","journal-title":"FEBS J."},{"key":"91955_CR62","doi-asserted-by":"publisher","first-page":"111353","DOI":"10.1016\/j.intimp.2023.111353","volume":"127","author":"TD Silva","year":"2024","unstructured":"Silva, T. D. et al. Matrix metalloproteinases inhibition reveals the association between inflammation, collagen accumulation and intestinal translocation of Schistosoma mansoni eggs in vivo. Int. Immunopharmacol. 127, 111353 (2024).","journal-title":"Int. Immunopharmacol."},{"key":"91955_CR63","unstructured":"Liang, Y.S., John, B.I. and Boyd, D.A. Laboratory Cultivation of Schistosome Vector Snails and Maintenance of Schistosome Life Cycles. 1st Sino-American Sympo-sium, Vol. 1, 34\u201348. References - Scientific Research Publishing. https:\/\/www.scirp.org\/(S(vtj3fa45qm1ean45vvffcz55))\/reference\/referencespapers.aspx?referenceid=3338726 (1987)."},{"key":"91955_CR64","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/B978-0-323-61211-1.00020-6","volume-title":"Comprehensive Dermatologic Drug Therapy","author":"SM Bhatia","year":"2024","unstructured":"Bhatia, S. M. & Hall, R. P. Dapsone. In Comprehensive Dermatologic Drug Therapy 4th edn (eds Bhatia, S. M. & Hall, R. P.) 222\u20132334 (Elsevier, 2024). https:\/\/doi.org\/10.1016\/B978-0-323-61211-1.00020-6.","edition":"4"},{"key":"91955_CR65","first-page":"325","volume":"51","author":"AR Ezzat","year":"2001","unstructured":"Ezzat, A. R., Seif El-Din, S. H. & Ebeid, F. A. Effect of praziquantel treatment on the activities of some liver microsomal enzymes in mice infected with Schistosoma mansoni. Arzneimittelforschung 51, 325\u2013331 (2001).","journal-title":"Arzneimittelforschung"},{"key":"91955_CR66","first-page":"328","volume":"39","author":"AW Cheever","year":"1968","unstructured":"Cheever, A. W. Conditions affecting the accuracy of potassium hydroxide digestion techniques for counting Schistosoma mansoni eggs in tissues. Bull. World Health Organ. 39, 328 (1968).","journal-title":"Bull. World Health Organ."},{"key":"91955_CR67","doi-asserted-by":"publisher","first-page":"483","DOI":"10.4269\/ajtmh.1967.16.483","volume":"16","author":"RH Duvall","year":"1967","unstructured":"Duvall, R. H. & DeWitt, W. B. An improved perfusion technique for recovering adult schistosomes from laboratory animals. Am. J. Trop. Med. Hyg. 16, 483\u2013486 (1967).","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"91955_CR68","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.jhep.2007.07.006","volume":"47","author":"ZD Goodman","year":"2007","unstructured":"Goodman, Z. D. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J. Hepatol. 47, 598\u2013607 (2007).","journal-title":"J. Hepatol."},{"key":"91955_CR69","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0659-5","author":"N Ruzehaji","year":"2015","unstructured":"Ruzehaji, N. et al. Combined effect of genetic background and gender in a mouse model of bleomycin-induced skin fibrosis. Arthritis Res. Ther. https:\/\/doi.org\/10.1186\/s13075-015-0659-5 (2015).","journal-title":"Arthritis Res. Ther."},{"key":"91955_CR70","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/jcmm.12428","volume":"19","author":"C Ippolito","year":"2015","unstructured":"Ippolito, C. et al. An integrated assessment of histopathological changes of the enteric neuromuscular compartment in experimental colitis. J. Cell Mol. Med. 19, 485\u2013500 (2015).","journal-title":"J. Cell Mol. Med."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91955-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91955-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91955-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T12:21:58Z","timestamp":1742991718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-91955-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["91955"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-91955-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,24]]},"assertion":[{"value":"11 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10084"}}