“The NET effect”: Neutrophil extracellular traps—a potential key component of the dysregulated host immune response in sepsis

Critical Care, Год журнала: 2025, Номер 29(1)

Опубликована: Фев. 4, 2025

Abstract Neutrophils release neutrophil extracellular traps (NETs) as part of a healthy host immune response. NETs physically trap and kill pathogens well activating facilitating crosstalk between cells complement. Excessive or inadequately resolved are implicated in the underlying pathophysiology sepsis other inflammatory diseases, including amplification response inducing thrombotic complications. Here, we review growing evidence implicating neutrophils central players dysregulated We discuss potential strategies for modifying to improve patient outcomes need careful selection.

Язык: Английский

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Identification of potential targets regulating neutrophil extracellular traps in acute rejection of kidney transplantation based on transcriptomics and animal experiments

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114008 - 114008

Опубликована: Янв. 5, 2025

Язык: Английский

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Inhibition of NETs prevents doxorubicin-induced cardiotoxicity by attenuating IL-18-IFN-γ-Cx43 axis induced cardiac conduction abnormalities

International Immunopharmacology, Год журнала: 2025, Номер 147, С. 114016 - 114016

Опубликована: Янв. 12, 2025

Язык: Английский

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GNGT1 remodels the tumor microenvironment and promotes immune escape through enhancing tumor stemness and modulating the fibrinogen beta chain-neutrophil extracellular trap signaling axis in lung adenocarcinoma

Translational Lung Cancer Research, Год журнала: 2025, Номер 14(1), С. 239 - 259

Опубликована: Янв. 1, 2025

Despite the recent advancements in treatment of cancer, 5-year survival patients with non-small cell lung cancer (NSCLC) remains unsatisfactory. Lung adenocarcinoma (LUAD) is NSCLC's most common subtype, and metastasis major cause death cancer. Therefore, identifying novel targets associated NSCLC crucial to improving treatment. This study aimed characterize expression GNGT1 LUAD clarify mechanism underlying association between higher level worse prognosis patients. The transcriptome datasets clinical information were obtained from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) database. Bioinformatics analyses performed 515 who stratified into two groups (high- low-GNGT1 group) according level. Overall survival, DNA promotor methylation, immune infiltration, gene set enrichment analysis (GSEA), Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway elucidate functions identify related hub genes LUAD. Their verified using tissues transgenic mice overexpressing under control a lung-specific promoter (Scgb1a1-Cre). was overexpressed poor prognosis. significantly correlated alteration hypomethylated status. High advanced lymph node degree infiltration. Functional indicated that differentially expressed (DEGs) high-GNGT1 group participated replication, replication preinitiation, M phase, while adhesion molecules, apoptosis, natural killer cell-mediated cytotoxicity all downregulated. Messenger RNA protein levels correspondingly regulated human Scgb1a1-Cre; LSL-GNGT1 mouse model (GNGT1fl/+ mice). tumor proliferation via enhancement stemness interaction driver genes. Elevated promoted epithelial-mesenchymal transformation, remodeled microenvironment, led metastasis, ultimately worsening survival-related

Язык: Английский

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Pulmozyme Ameliorates LPS-Induced Lung Fibrosis but Provokes Residual Inflammation by Modulating Cell-Free DNA Composition and Controlling Neutrophil Phenotype

Biomolecules, Год журнала: 2025, Номер 15(2), С. 298 - 298

Опубликована: Фев. 17, 2025

Pulmonary fibrosis, a chronic progressive lung disorder, can be the result of previous acute inflammation-associated injury and involves wide variety inflammatory cells, causing deposition extracellular matrix (ECM) components in lungs. Such is often associated with excessive neutrophil function formation DNA networks lungs, which are also some most important factors for fibrosis development. Acute subsequent was initiated C57Bl/6 mice by single intranasal (i.n.) administration LPS. Starting from day 14, human recombinant DNase I form Pulmozyme topical instilled i.n. twice week at dose 50 U/mouse. Cell-free (cfDNA), activity, cell content were analyzed blood serum bronchoalveolar lavage fluid (BALF). Inflammatory fibrotic changes tissue evaluated histological analysis. The gene expression profile spleen-derived neutrophils RT-qPCR. We demonstrated that significantly reduced connective expansion However, despite reliable antifibrotic effect, complete resolution inflammation respiratory system treated not achieved, possibly due to enhanced granulocyte recruitment nuclear/mitochondrial cfDNA balance BALF. Moreover, introduction caused enrichment population those an unusual phenotype, combining pro-inflammatory anti-inflammatory features, maintain inflammation. considered promising drug management; however, therapy may accompanied residual

Язык: Английский

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Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(2), С. 133 - 133

Опубликована: Фев. 19, 2025

Cellular nucleosomes-the structural and functional units of chromatin-are inherently present in cells. During cellular damage or cell death, nucleosomes are released into circulation, either actively passively. Once released, can become immunogenic entities through various mechanisms. The nucleosomal proteins nucleosomes, called histones, play a pivotal role inducing immunogenicity. However, intact more than the histones alone, as double-stranded deoxyribonucleic acid (dsDNA) enhances its potential. Our recent study has shown that circulating predominantly rather free histones. Consequently, primarily function integral parts acting independently. Circulating their associated implicated pathogenesis wide array diseases. Notably, they critical lung injury sepsis. These diseases have high morbidity mortality rates lack early diagnostic biomarkers. Further investigation is required to fully elucidate disease processes. This review aims discuss current understanding sepsis, with focus on underlying

Язык: Английский

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Archaea-inspired deoxyribonuclease I liposomes prevent multiple organ dysfunction in sepsis

Journal of Controlled Release, Год журнала: 2025, Номер 380, С. 1109 - 1126

Опубликована: Фев. 26, 2025

Язык: Английский

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Pathogenetic association of inflammation and hemostasis markers in the blood of patients with injuries of large joints

TRAUMA, Год журнала: 2025, Номер 26(1), С. 1 - 10

Опубликована: Март 7, 2025

Background. In patients with injuries of large joints, the activation inflammation causes risk thrombophilia. The prediction thrombotic complications and their prevention can improve quality treatment. purpose: to investigate data scientific medical literature on pathogenetic association between markers hemostasis in degenerative diseases post-traumatic joints. Materials methods. search for has been made PubMed database 10 years. Sixty works were selected. Results. A total 60 papers selected analysis. They recorded information about relationship mechanisms hypercoagulability trauma. specified are given this work. Conclusions. orthopedics traumatology, considerable attention is paid surgical treatment trauma, particular, Individuals trauma or surgery joints have a correlation biochemical common clinical inflammation, metabolism glycoproteins, proteoglycans collagen laboratory indicators hemostasis. case, significant damage formation vicious circle observed: decrease plasminogen content, which under action activators converted plasmin, trigger factor fibrinolytic system, that at same time activity acceleration dystrophic processes accumulation blood serum an excessive amount acute phase glycoproteins. addition, there increase plasma following coagulation markers: fibrinogen, soluble fibrin monomer complexes, D-dimers, inflammatory such as C-reactive protein, haptoglobin. From this, it follows postoperative requires timely monitoring markers, well measures prevent thrombophilia, including prehospital stage.

Язык: Английский

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Neutrophil extracellular traps-triggered hepatocellular senescence exacerbates lipotoxicity in non-alcoholic steatohepatitis

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Neutrophils are initial responders in inflammation and contribute to non-alcoholic fatty liver disease (NAFLD) progression steatohepatitis (NASH). Neutrophil extracellular traps (NETs) implicated injury, yet their precise mechanisms NASH remains unclear. This study investigates how NETs drive by disrupting hepatocyte lipotoxicity explore the regulatory mechanism of formation its downstream effects on pathology. Clinical samples from patients diet-induced mice were analyzed for NET levels. pharmacologically inhibited, senescent cells selectively eliminated mice. Myeloid-specific RBP-J knockout generated disrupt Notch signaling, with subsequent evaluation formation, senescence markers, steatosis, fibrosis, inflammation. elevated mice, correlating lipotoxicity. Pharmacological disruption reduced senescence, accompanied attenuated steatosis fibrosis. Senescent cell clearance replicated these improvements, confirming emerges is a vital step promote NASH. signaling ablation suppressed generation, concurrently decreasing lipid deposition Our findings elucidate novel which neutrophil-derived driven exacerbate promoting thereby contributing hepatic insight may provide potential intervention strategies therapeutic targets treatment.

Язык: Английский

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The emerging role of neutrophil extracellular traps in autoimmune and autoinflammatory diseases

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Март 1, 2025

Neutrophil extracellular traps (NETs) are unique fibrous structures released by neutrophils in response to various pathogens, exhibiting both anti-inflammatory and proinflammatory effects. In autoimmune conditions, NETs serve as crucial self-antigens triggering inflammatory cascades activating the inflammasome complement systems, disrupting self-tolerance mechanisms accelerating responses. Furthermore, play a pivotal role modulating immune cell activation, affecting adaptive This review outlines intricate relationship between diseases, including arthritis, systemic Behçet's disease, lupus erythematosus, kidney skin sclerosis, vasculitis, gouty arthritis. It highlights potential of targeting therapeutic strategy diseases. By examining dynamic balance NET formation clearance this offers critical insights theoretical foundation for future research on NET-related mechanisms. Advances systems biology, flow cytometry, single-cell multiomics sequencing have provided valuable tools exploring molecular NETs. These advancements renewed focus offering promising avenues further investigation into their clinical implications.

Язык: Английский

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