{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T20:04:37Z","timestamp":1788984277584,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81401498"],"award-info":[{"award-number":["81401498"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204542"],"award-info":[{"award-number":["82204542"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271252"],"award-info":[{"award-number":["82271252"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Neutrophil extracellular traps (NETs) act as a vital first line of defence against tissue damage and pathogens, playing a significant role in improving diseases such as intestinal ischemia reperfusion injury (IRI). However, we observed that after intestinal injury, intestinal bacteria and lipopolysaccharides (LPS) can enter the circulatory system, leading to a significant secondary increase in NETs production and the subsequent activation of a coagulation cascade. This phenomenon contributes to a pathological process known as the \u2018second strike\u2019 of NETs, which exaggerates intestinal damage and microcirculation disturbance. Selectively mitigating the detrimental effects associated with this second strike presents a promising therapeutic strategy. We developed an innovative conjugate of stroke\u2010homing peptide (SHp) and DNase1 (SHp\u2010DNase1) to enhance the stability of DNase in the bloodstream while selectively targeting NETs in thromboembolic events. The effects of SHp\u2010DNase1 on blood flow, ischemia, and vascular leakage were evaluated in a mouse model using laser Doppler flowmetry and an in\u00a0vivo imaging system. Levels of LPS and NETs were elevated in patients with IRI. Similarly, the expression of NETs and LPS was upregulated in mice with intestinal IRI. In\u00a0vivo imaging revealed disturbances in intestinal microcirculation, accompanied by intestinal leakage, which were effectively reversed by the administration of SHp\u2010DNase1. Almost all of the SHp\u2010DNase1 localised to the gastrointestinal tract, demonstrating the effective targeting of DNase1 to the site of intestinal injury via SHp guidance. Furthermore, the combination of SHp\u2010DNase1 and CRO significantly reduced the expression of ischemia\u2010inducible factors, leading to a marked decrease in mortality in the mouse model. These findings suggest that intestinal LPS leakage correlated with NETs exacerbation plays a critical role in IRI. The combination of SHp\u2010DNase1 and CRO is an effective treatment strategy by simultaneously controlling inflammation and addressing microcirculatory disorders induced by NETs in the therapy of IRI.<\/jats:p>","DOI":"10.1111\/cpr.70010","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:54:31Z","timestamp":1741719271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Stroke\u2010Homing Peptide\u2010<scp>DNase1<\/scp> Alleviates Intestinal Ischemia Reperfusion Injury by Selectively Degrading Neutrophil Extracellular Traps"],"prefix":"10.1111","volume":"58","author":[{"given":"Tingting","family":"Liu","sequence":"first","affiliation":[{"name":"Graduate College of Dalian Medical University  Dalian Liaoning China"},{"name":"Department of Interventional and Vascular Surgery The Third Affiliated Hospital of Nanjing Medical University (Changzhou Second People's Hospital)  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinrong","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuting","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghui","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical University  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Shanghai General Hospital of Nanjing Medical University  Shanghai China"},{"name":"Department of Gastroenterology Lianyungang Municipal Oriental Hospital  Lianyungang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Liu","sequence":"additional","affiliation":[{"name":"Innovation Center of Suzhou Nanjing Medical University  Suzhou Jiangsu China"},{"name":"National Center of Technology Innovation for Biopharmaceuticals  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Basic Medical Science Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongzhi","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Interventional and Vascular Surgery The Third Affiliated Hospital of Nanjing Medical University (Changzhou Second People's Hospital)  Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2017.68535"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.71491"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00112.2013"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.05.048"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u2010981\u201015\u20102385\u20104_11"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2017.11.041"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jflm.2011.12.023"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5221"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2022.09.004"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239\u2010020\u201002324\u2010z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102906"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000005810"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1bm01591e"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201015807\u20106"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010018\u201036198\u20102"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2008.07.020"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104499"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2017.07.027"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hlc.2016.10.012"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201041147\u20103"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155182"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12931\u2010024\u201002676\u20107"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.125370"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002898"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2468\u20101253(19)30264\u2010x"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology9120418"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e31377"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000011782"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073787"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13538"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7673"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.33.783"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0924\u20108579(02)00160\u20107"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.09.021"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.75"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2023.130305"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13010083"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.4149\/bll_2020_141"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010021\u201000745\u20100"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1181761"}],"container-title":["Cell Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.70010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:25:47Z","timestamp":1754907947000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.70010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":42,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1111\/cpr.70010"],"URL":"https:\/\/doi.org\/10.1111\/cpr.70010","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"assertion":[{"value":"2024-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70010"}}