{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:46Z","timestamp":1790315986704,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":266,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pulmonary fibrosis (PF) secondary to\n                      <jats:italic>Echinococcus granulosus<\/jats:italic>\n                      infection is a severe complication with limited therapeutic options. Harmine (HM) exhibits antifibrotic potential but is restricted by significant neurotoxicity. This study aimed to evaluate the therapeutic efficacy and underlying mechanism of HM derivative H\u20102\u2010104 in a clinically relevant\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      \u2010induced PF mouse model, and to clarify its advantages over parent compound HM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A mouse model of\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      \u2010induced PF was established, and treated with H\u20102\u2010104 (25 or 50\u2009mg\/kg) or nintedanib for 21 days. Lung function, histopathology, hydroxyproline (HYP), inflammatory cytokines, and fibrosis\u2010related protein expression were assessed. In vitro, human embryonic lung fibroblasts (MRC\u20105) were activated with TGF\u2010\u03b21 and treated with H\u20102\u2010104. Cell viability, migration, apoptosis, differentiation, DNA damage, and related gene expression were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      H\u20102\u2010104 significantly improved lung function, alleviated pathological damage, and collagen deposition, decreased HYP, TGF\u2010\u03b21, TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2, elevated IL\u201010, and downregulated \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), collagen I, and fibronectin. Importantly, H\u20102\u2010104 showed no obvious neurotoxicity and exhibited better safety than HM. In vitro, H\u20102\u2010104 inhibited TGF\u2010\u03b21\u2010induced MRC\u20105 cell viability (IC\n                      <jats:sub>50<\/jats:sub>\n                      \u2009=\u200913.49\u2009\u00b5g\/mL), migration, and fibroblast\u2010to\u2010myofibroblast differentiation, while promoting apoptosis along with increased DNA damage in a dose\u2010dependent manner. Additionally, H\u20102\u2010104 downregulated the expression of fibrosis\u2010related genes and upregulated DNA damage\u2010related genes (\n                      <jats:italic>H2AX<\/jats:italic>\n                      ,\n                      <jats:italic>ATR<\/jats:italic>\n                      , and\n                      <jats:italic>RAD51<\/jats:italic>\n                      ) in TGF\u2010\u03b21\u2010induced MRC\u20105 cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study establishes H\u20102\u2010104 as a promising antifibrotic candidate for\n                      <jats:italic>E. granulosus<\/jats:italic>\n                      \u2010induced PF, using a clinically meaningful parasitic infection\u2010associated fibrosis model. H\u20102\u2010104 retains strong antifibrotic efficacy while overcoming the neurotoxicity limitation of HM. Mechanistically, the activation of DNA damage response is correlated with the antifibrotic activities of H\u20102\u2010104, providing a new perspective for targeting fibroblast activation in PF therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jimr\/8865338","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:31:32Z","timestamp":1790314292000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harmine Derivative H\u20102\u2010104 Alleviates\n                    <i>Echinococcus granulosus<\/i>\n                    \u2010Induced Pulmonary Fibrosis in Mice by Inhibiting Fibroblast Activation and Inducing DNA 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