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neutrophil extracellular traps mediate neuro-immunothrombosis

Neural Regeneration Research 2024年第8期19卷 1734-1740页

作者： Jianbo Lou Jianning Zhang Quanjun Deng Xin Chen Department of Neurosurgery Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institute Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous SystemMinistry of EducationTianjin Key Laboratory of InjuriesVariations and Regeneration of Nervous SystemTianjinChina

neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry *** extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation ***,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and *** summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic *** blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological *** research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of ***,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain *** review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.

关键词： inflammation neuro-immunothrombosis neurologic diseases neurotrauma neutrophil extracellular traps platelet thrombosis traumatic brain injury

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Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

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BIOCELL 2024年第1期48卷 9-19页

作者： YANG LI JIAN LIU YUEDI HU CHENGZHI CONG YIMING CHEN QIAO ZHOU Department of Rheumatology The First Affiliated Hospital of Anhui University of Chinese MedicineHefei230031China First Clinical Medical School Anhui University of Chinese MedicineHefei230031China Institute of Rheumatology Anhui Academy of Chinese MedicineHefei230031China

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint *** are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of *** extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune *** have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint *** article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

关键词： Rheumatoid arthritis neutrophil extracellular traps Review

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neutrophil extracellular traps participate in the development of cancer-associated thrombosis in patients with gastric cancer

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World Journal of Gastroenterology 2022年第26期28卷 3132-3149页

作者： Jia-Cheng Li Xiao-Ming Zou Shi-Feng Yang Jia-Qi Jin Lei Zhu Chang-Jian Li Hao Yang An-Ge Zhang Tian-Qi Zhao Chong-Yan Chen Department of Gastrointestinal Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina The Key Laboratory of Myocardial Ischemia Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina Department of Neurosurgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150001Heilongjiang ProvinceChina

BACKGROUND The development of venous thromboembolism(VTE) is associated with high mortality among gastric cancer(GC) patients. neutrophil extracellular traps(NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC *** To investigate the effect of NETs on the development of cancer-associated thrombosis in GC *** The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells(ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity(PCA) was determined by fibrin formation and thrombin–antithrombin complex(TAT) *** in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava(IVC).RESULTS NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and Pselectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumorbearing mice compared with control mice. Notably, the combination of deoxyribonuclease I,activated protein C, and sivelestat markedly abolished the PCA of *** GC-induced NET

关键词： neutrophil extracellular traps Gastric cancer Platelet Endothelial cells Venous thromboembolism

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Blood neutrophil extracellular traps:a novel target for the assessment of mammary health in transition dairy cows

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Journal of Animal Science and Biotechnology 2023年第3期14卷 1068-1079页

作者： Luyi Jiang Huizeng Sun Fengfei Gu Jin He Fengqi Zhao Jianxin Liu Institute of Dairy Science College of Animal SciencesZhejiang UniversityHangzhouChina Ministry of Education Key Laboratory of Molecular Animal Nutrition Zhejiang UniversityHangzhouChina Institute of Animal Genetics and Reproduction College of Animal SciencesZhejiang UniversityHangzhouChina Department of Animal&Veterinary Sciences University of VermontBurlingtonUSA

Background:Mammary health is important for transition dairy cows and has been well recognized to exert decisive effects on animal ***,the factors influencing mammary health are still *** somatic cell count(DSCC)could reflect the mastitis risk since it is the percentage of neutrophils plus lymphocytes in total somatic cells and could be reflective of mammary health of dairy *** work aimed to investigate the assessment and prognosis of the health of transition cows based on blood neutrophil extracellular traps(NETs).Results:Eighty-four transition Holstein dairy cows were *** serum was sampled in all the animals at week 1 pre-and postpartum,and milk was sampled at week 1 *** on the DSCC in milk at week 1,cows with lower(7.4%±4.07%,n=15)and higher(83.3%±1.21%,n=15)DSCCs were *** DSCC cows had higher levels of red blood cell counts(P<0.05),hemoglobin(P=0.07),and hematocrit(P=0.05),higher concentrations of serum oxidative variables[reactive oxygen species(P<0.05),malondialdehyde(P<0.05),protein carbonyl(P<0.05),and 8-hydroxy-2-deoxyguanosine(P=0.07)],higher levels of serum and milk NETs(P<0.05)and blood-milk barrier indicators,including serumβ-casein(P=0.05)and milk immunoglobulin G2(P=0.09),than those of low DSCC *** addition,lower concentrations of serum nutrient metabolites(cholesterol and albumin)(P<0.05)and a lower level of serum deoxyribonuclease I(P=0.09)were observed in high DSCC cows than in low DSCC *** the assessments performed using levels of the three prepartum serum parameters(NETs,deoxyribonuclease I andβ-casein),the area under the curve(0.973)of NETs was the *** addition,the sensitivity(1.00)and specificity(0.93)were observed for the discrimination of these cows using NETs levels with a critical value of 32.2 ng/mL(P<0.05).Conclusions:The formation of NETs in blood in transition dairy cows may damage the integrity of the blood-milk barrier and thereby increase the risk for

关键词： Blood-milk barrier Differential somatic cell count Mastitis risk neutrophil extracellular traps

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Role of neutrophil extracellular traps in inflammatory evolution in severe acute pancreatitis

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Chinese Medical Journal 2022年第23期135卷 2773-2784页

作者： Hongxin Kang Yue Yang Lv Zhu Xianlin Zhao Juan Li Wenfu Tang Meihua Wan Department of Integrated Traditional Chinese and Western Medicine National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

Severe acute pancreatitis(SAP)is a life-threatening acute abdominal disease with two peaks of death:the first in the early stage,characterized by systemic inflammatory response-associated organ failure;and the second in the late stage,characterized by infectious *** are the main immune cells participating in the whole process of *** addition to the traditional recognition of neutrophils as the origination of chemokine and cytokine cascades or phagocytosis and degranulation of pathogens,neutrophil extracellular traps(NETs)also play an important roles in inflammatory *** reviewed the role of NETs in the occurrence and development of SAP and its fatal complications,including multiple organs injury,infected pancreatic necrosis,and *** review provides novel insights into the involvement of NETs throughout the entire process of SAP,showing that targeting NETs might be a promising strategy in SAP ***,precision therapeutic options targeting NETs in different situations require further investigation.

关键词： Inflammation neutrophil extracellular traps Organ injury Sepsis Severe acute pancreatitis Thrombus

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Hypobaric Hypoxia Aggravates Renal Injury by Inducing the Formation of neutrophil extracellular traps through the NF-κB Signaling Pathway

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当代医学科学(英文) 2023年第3期43卷 469-477页

作者： Jun-yu WEI Miao-yue HU Xiu-qi CHEN Jin-shuang WEI Jie CHEN Xuan-kai QIN Feng-ying LEI Jia-sen ZOU Shi-qun ZHU Yuan-han QIN Department of Pediatrics the First Affiliated HospitalGuangxi Medical UniversityNanning 530021China Children's Hospital of Chongqing Medical University Chongqing 400015China Shenzhen Children's Hospital Shenzhen 518034China

Objective The hypersensitivity of the kidney makes it susceptible to hypoxia *** involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been *** this study,we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying *** A total of 24 SD male rats were divided into three groups(n=8 each):normal control group,hypoxia group and hypoxia+pyrrolidine dithiocarbamate(PDTC)*** in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters(oxygen partial pressure about 6.9 kPa)for 7 *** was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 *** changes of the rat renal tissues were observed under a light microscope;the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cell-free DNA(cf-DNA)and reactive oxygen species(ROS)were measured;the expression levels of myeloperoxidase(MPO),citrullinated histone H3(cit-H3),B-cell lymphoma 2(Bcl-2),Bax,nuclear factor kappa B(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in rat renal tissues were detected by qRT-qPCR and Western blotting;the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical *** After hypoxia,the expression of NF-κB protein in renal tissues was significantly increased,the levels of SCr,BUN,cf-DNA and ROS in serum were significantly increased,the formation of NETs in renal tissues was significantly increased,and a large number of tubular dilatation and lymphocyte infiltration were observed in renal *** PDTC was used to inhibit NF-κB activation,NETs formation in renal tissue was significantly decreased,the expression level of Bcl-2 in renal tissues was significantly increased,the expres

关键词： hypobaric hypoxia neutrophil extracellular traps hypoxia kidney injury NF-κB apoptosis

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neutrophil extracellular traps mediate the crosstalk between glioma progression and the tumor microenvironment via the HMGB1/RAGE/IL-8 axis

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Cancer Biology & Medicine 2020年第1期17卷 154-168页

作者： Caijun Zha Xiangqi Meng Lulu Li Shan Mi Da Qian Ziwei Li Pengfei Wu Shaoshan Hu Shihong Zhao Jinquan Cai Yanhong Liu Department of Laboratory Diagnosis The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Department of Neurosurgery The Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Neuroscience Institute Heilongjiang Academy of Medical SciencesHarbin 150086China

Objective:neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of ***,the mechanisms underlying the involvement of NETs in glioma progression remain largely *** study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor ***:neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically *** effects of NETs on glioma cell progression were studied in a co-culture *** vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of ***:neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade *** induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and *** overproduction promoted glioma cell proliferation,migration,and ***,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in *** addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in ***,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in ***:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 *** NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.

关键词： neutrophil extracellular traps HMGB1 IL-8 NF-κB glioma microenvironment

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neutrophil extracellular traps in Autoimmune Diseases

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Chinese Medical Journal 2018年第13期131卷 1513-1519页

作者： Yi He Fang-Yuan Yang Er-Wei Sun Department of Rheumatology and Immunology The Third Affiliated Hospital Southern Medical University Guangzhou Guangdong 510630 China Institute of Clinical Immunology Academy of Orthopedics Guangdong Province Guangzhou Guangdong 510630 China Southern Medical University Guangzhou Guangdong 510630 China

INTRODUCTIONIn 2004, NETosis was first reported as an important step to kill bacteria by neutrophils. During the process ofN ETosis, neutrophil extracellular traps （NETs） that contain large web-like structures of decondensed chromatin decorated with histones and intracellular components, including neutrophil elastase （NE）, myeloperoxidase （MPO）, high mobility group protein B I （HMGBI）, and proteinase 3 （PR3）, are extruded into the extracellular space, The structures of NETs enable the neutrophil to potently catch and kill pathogens at the site of inflammation. Furthermore, increasing studies have identified the presence of NETs in autoimmune diseases. NETs deliver multiple autoantigens to host immtme system that induce autoimmune responses and directly release damage-associated molecular patterns to amplify inflammatory responses. Therefore, NETs are commonly described to play a crucial role in the pathogenesis and development of autoimmune diseases in recent years.

关键词： Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Autoimmunity neutrophil extracellular traps RheumatoidArthritis Systemic Lupus Erythematosus

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neutrophil extracellular traps in the intestinal mucosa of Eimeria-infected animals

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Asian Pacific Journal of Tropical Biomedicine 2016年第4期6卷 301-307页

作者： Tamara Munoz-Caro Liliana Machado Ribeiro da Silva Zaida Renteria-Solis Anja Taubert Carlos Hermosilla Institute of Parasitology Justus Liebig University Giessen

Objective:To investigate the presence of neutrophil extracellular traps(NETs) in vivo by analysing intestinal sections from experimentally Eimeria bovis-and naturally Eimeria arloingi-infected ***:Intestinal samples of Eimeria arloingi-and Eimeria bovis-infected animals were analysed by using immunohistochemical and fluorescence approach by using monoclonal ***:Classical NET components were confirmed by co-localization of extracellular DNA being decorated with neutrophil elastase and histones in Eimeria-infected tissue ***,extrusion of NETs was exclusively detected in intestinal polymorphonuclear neutrophils infiltrating Eimeria-infected *** vivo NETs were either found in close proximity or in direct contact to different Eimeria stages suggesting a stage-independent *** were also found within the gut lumen driven by polymorphonuclear neutrophils that were contacting released ***:We postulate that NETs might play an important role in innate defence reactions in coccidiosis therefore significantly altering the outcome of infection.

关键词： Eimeria bovis Eimeria arloingi neutrophil extracellular traps Apicomplexa Coccidiosis

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neutrophil extracellular traps in gastrointestinal cancer

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World Journal of Gastroenterology 2021年第33期27卷 5474-5487页

作者： Zi-Qiang Chu Ke-Cheng Zhang Lin Chen Graduate School Chinese PLA General HospitalBeijing 100853China Institute of Basic Medical Sciences Chinese PLA General HospitalBeijing 100853China Department of General Surgery Chinese PLA General Hospital First Medical CenterBeijing 100853China

Gastrointestinal(GI)cancer is a high-risk malignancy and is characterized by high mortality and morbidity *** extracellular traps(NETs),a weblike structure consisting of chromatin DNA with interspersed cytoplasmic and granule proteins,are extruded by activated neutrophils to entrap and kill bacteria and ***,accumulating evidence shows that NETs are related to the progression and metastasis of *** clinical studies,NETs infiltrate primary GI cancer tissues and are even more abundant in metastatic *** quantity of NETs in peripheral blood is revealed to be associated with ascending clinical tumour stages,indicating the role of NETs as a prognostic markers in GI ***,several inhibitors of NETs or NET-related proteins have been discovered and used to exert anti-tumour effects in vitro or in vivo,suggesting that NETs can be regarded as targets in the treatment of GI *** this review,we will focus on the role of NETs in gastric cancer and colorectal cancer,generalizing their effects on tumour-related thrombosis,invasion and *** reports are also listed to show the latest evidences of how NETs affect GI ***,notwithstanding the scarcity of systematic studies elucidating the underlying mechanisms of the interaction between NETs and cancer cells,we highlight the potential importance of NETs as biomarkers and anti-tumour therapeutic targets.

关键词： neutrophil extracellular traps Gastric cancer Colorectal cancer Biomarkers Therapeutic targets

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