Metabolic landscape in venous thrombosis: insights into molecular biology and therapeutic implications

Annals of Medicine, Год журнала: 2024, Номер 56(1)

Опубликована: Сен. 19, 2024

The findings of the last decade suggest a complex link between inflammatory cells, coagulation, and activation platelets their synergistic interaction to promote venous thrombosis. Inflammation is present throughout process thrombosis, various metabolic pathways erythrocytes, endothelial immune cells involved in including glucose metabolism, lipid homocysteine oxidative stress, are associated with inflammation. While microenvironment has been identified as marker malignancy, recent studies have revealed that for cancer alterations appear also be potential risk. In this review, we discuss how synergy metabolism thrombosis drives thrombotic disease. We explore great anti-inflammatory strategies targeting anti-inflammation metabolism. Furthermore, can use our existing knowledge reduce risk

Язык: Английский

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Established and emerging roles for mitochondria in neutrophils

Immunological Reviews, Год журнала: 2022, Номер 314(1), С. 413 - 426

Опубликована: Ноя. 4, 2022

Summary Neutrophils are the most abundant innate immune cells in human blood, emerging as important players a variety of diseases. Mitochondria bioenergetic, biosynthetic, and signaling organelles critical for cell fate function. have been overlooked neutrophil research owing to conventional view that neutrophils contain few, if any, competent mitochondria do not rely on these adenosine triphosphate production. A growing body evidence suggests participate biology at many levels, ranging from development chemotaxis, effector function, death. Moreover, mitochondrial components, such deoxyribonucleic acid, can be released by eliminate infection and/or shape response, depending specific context. In this review, we provide an update functional role neutrophils, highlight key modulating phenotype function during inflammation, discuss possibilities challenges exploit unique aspects disease treatment.

Язык: Английский

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Endoplasmic Reticulum Stress in Systemic Lupus Erythematosus and Lupus Nephritis: Potential Therapeutic Target

Journal of Immunology Research, Год журнала: 2023, Номер 2023, С. 1 - 12

Опубликована: Авг. 31, 2023

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Approximately one-third to two-thirds of the patients with SLE progress nephritis (LN). The pathogenesis and LN has not yet been fully elucidated, effective treatment for both conditions lacking. endoplasmic reticulum (ER) largest intracellular organelle site protein synthesis, lipid metabolism, calcium storage. Under stress, function ER disrupted, accumulation unfolded or misfolded proteins occurs in ER, resulting an stress (ERS) response. ERS involved dysfunction B cells, macrophages, T dendritic neutrophils, other immune causing system disorders, such as SLE. In addition, also renal resident cell injury contributes progression LN. molecular chaperones, autophagy, proteasome degradation pathways inhibit restore homeostasis improve cells injury. This may be therapeutic strategy this review, we summarize advances field.

Язык: Английский

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Histones in Neutrophil Extracellular Traps (Nets) Contain Oxidative Post-Translational Modifications Induced by the Myeloperoxidase Oxidant Hypochlorous Acid

Опубликована: Янв. 1, 2025

Язык: Английский

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Neutrophils Display Novel Partners of Cytosolic Proliferating Cell Nuclear Antigen Involved in Interferon Response in COVID-19 Patients

Journal of Innate Immunity, Год журнала: 2025, Номер 17(1), С. 154 - 175

Опубликована: Фев. 27, 2025

Introduction: Neutrophils are key players in the hyperinflammatory response during SARS-CoV-2 infection. The cytosolic proliferating cell nuclear antigen (PCNA) is a scaffolding protein highly dependent on microenvironment status and known to interact with numerous proteins that regulate neutrophil functions. This study aimed examine content PCNA interactome neutrophils from COVID-19 patients. Methods: Proteomic analyses were performed cytosols healthy donors patients severe or critical COVID-19. In vitro approaches used explore biological significance of COVID-19-specific interactome. Results: Neutrophil cytosol analysis revealed strong interferon (IFN) signature, variations according disease severity. Interactome identified associations involved signaling, cytoskeletal organization, extracellular trap (NET) formation, such as arginine deiminase type-4 (PADI4) histone H3, particularly Functional studies signaling showed T2AA, scaffold inhibitor, downregulated IFN-related genes, including STAT1, MX1, IFIT1, IFIT2 neutrophils. Additionally, T2AA specifically inhibited secretion CXCL10, an IFN-dependent cytokine. was also found effector implicated NET especially cases. Conclusion: has unveiled new partners enhance pathway, thereby modulating immune responses contributing hyperinflammation These findings provide valuable insights into dysregulation other immune-related conditions.

Язык: Английский

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Neospora caninum triggers the release of heterophil extracellular traps in chickens

Veterinary Parasitology, Год журнала: 2025, Номер 337, С. 110471 - 110471

Опубликована: Апрель 15, 2025

Язык: Английский

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Neutrophil-to-lymphocyte ratio predicts a poor prognosis for penile cancer with an immunosuppressive tumor microenvironment

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Chronic inflammation related to poor genital hygiene is a well-recognized pathogenic trigger for penile cancer (PC). The neutrophil-to-lymphocyte ratio (NLR) simple, reproducible systemic inflammatory marker and has been reported indicate unfavorable outcomes. However, previous studies were limited by small sample sizes, confounding prognostic factors lack of high-quality evidence demonstrating the significance NLR in PC. A large multicenter cohort 582 PC patients who underwent radical inguinal lymphadenectomy with definitive pN stage information was assessed. Univariate multivariate Cox regression analyses performed investigate value inflammation-related markers. Propensity score matching (PSM) used minimize clinicopathological features. Immunofluorescence assess immunosuppressive tumor microenvironment (TME). high preoperative (≥ 3.0) associated advanced pT, pN, pathological grade lymphovascular invasion patients. After PSM eliminate interference from clinical factors, found be independent indicators (both p<0.001). NLRs had shorter progression-free survival (PFS) poorer cisplatin-based chemotherapy PD-1 immunotherapy response. We also that proinflammatory cytokine secretion increased N2 tumor-associated neutrophils (TANs) infiltration CD8+ T-cell exhaustion TME. TANs induced neutrophil extracellular trap formation might contribute progression resistance high-NLR an effective, simple indicator TME

Язык: Английский

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Histones in neutrophil extracellular traps (NETs) contain oxidative post-translational modifications induced by the myeloperoxidase oxidant hypochlorous acid.

Redox Biology, Год журнала: 2025, Номер 84, С. 103696 - 103696

Опубликована: Май 23, 2025

Extracellular traps (NETs) released by neutrophils during inflammation play a role in clearing infection but also contribute to disease pathology. NETs consist of DNA backbone containing histones, anti-microbial granule proteins, such as myeloperoxidase (MPO), and other proteins. MPO remains enzymatically active generates hypochlorous acid (HOCl) kill pathogens. However, HOCl readily reacts with whether histones NET proteins are modified this oxidant is unknown. This significant post-translational modification alters their intracellular extracellular reactivity. In study, we used proteomic approach characterise the protein composition identify HOCl-induced oxidative modifications on were collected from primary PLB-985 cell line stimulated phorbol myristate acetate (PMA) or nigericin, bacterial peptide derived Streptomyces hygroscopicus. There was evidence for Lys nitrile aminoadipic semialdehyde formation, Tyr Trp chlorination, Met oxidation including quinone oxidoreductase. Chlorination Tyr-88 histone H4 particularly abundant occurred greater extent exposed PMA compared consistent nigericin triggering release via non-oxidative pathway. observed nuclear cytoplasmic extracts cells could be decreased treatment inhibitor AZD5904. These findings provide first that modifies within NETs, H4, which may relevant disease.

Язык: Английский

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Association of neutrophil/high-density lipoprotein cholesterol ratio with the cardiovascular-kidney-metabolic syndrome and its cardiovascular mortality

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Июнь 4, 2025

Background Cardiovascular-kidney-metabolic (CKM) syndrome is a novel multi-system disease defined by the American Heart Association (AHA). This study aims to investigate associations between neutrophil/high-density lipoprotein cholesterol ratio (NHR) and CKM its association with cardiovascular (CVD) mortality. Methods The data for this were derived from National Health Nutrition Examination Survey (NHANES) conducted 2005 2018 Death Index (NDI) database. Weighted multivariate logistic regression Cox primary analytical methods. restricted cubic spline (RCS) subgroup analyses also carried out. Results A total of 13,165 participants included in study. weighted mean NHR was 3.14 ± 0.03. prevalence rate 17.36%. results indicated that there positive (OR per SD : 1.25, 95% CI: 1.10–1.42, p &lt; 0.001). Among quartile groups NHR, showed an increase ( trend &lt;0.0001). individuals syndrome, demonstrated significantly predicted CVD mortality (HR 1.31, 1.14–1.50, risk increased = 0.01). Furthermore, RCS analysis linear (non-linear 0.075) 0.300). suggested relationship outcomes robust, no significant interaction. Conclusion Our demonstrates not only associated but serves as effective predictor patients syndrome. provides new insights into clinical identification prognostic evaluation

Язык: Английский

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Enoxaparin improves COVID-19 by reducing Neutrophils Extracellular Traps (NETs) production

Clinical Immunology, Год журнала: 2023, Номер 257, С. 109836 - 109836

Опубликована: Ноя. 10, 2023

Язык: Английский

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