1.Research progress on the impact and mechanism of neutrophil extracellular traps (NETs) components in atherosclerosis.
Xin CHEN ; Jing-Jing ZHU ; Xiao-Fan YANG ; Yu-Peng MA ; Yi-Min BAO ; Ke NING
Acta Physiologica Sinica 2025;77(1):107-119
Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.
Extracellular Traps/physiology*
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Humans
;
Atherosclerosis/immunology*
;
Neutrophils/physiology*
;
Leukocyte Elastase/metabolism*
;
Peroxidase/physiology*
;
Matrix Metalloproteinases/physiology*
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Cathepsin G/metabolism*
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Cathelicidins
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HMGB1 Protein/physiology*
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Histones
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Animals
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Endothelium, Vascular
2.Research progress on mechanism of traditional Chinese medicine in regulating neutrophil extracellular traps in prevention and treatment of metabolic diseases.
Sai ZHANG ; Ming-Yuan FAN ; Jiu-Shu YUAN ; Qi-Yuan YAO ; Hong-Yan XIE ; Hai-Po YUAN ; Hong GAO
China Journal of Chinese Materia Medica 2025;50(1):78-93
Metabolic diseases have seen a steady increase in incidence in recent years, becoming one of the main causes of sub-health status globally. Neutrophil extracellular traps(NETs) are reticular complexes containing DNA, which trap foreign microorganisms or induce an immune response. Current research indicates that NETs are widely active in various metabolic diseases and can cause severe damage to the body through multiple mechanisms, including promoting blood glucose elevation, damaging vascular endothelial cells, forming vascular embolisms, triggering intense inflammation, and promoting lipid accumulation. Therefore, intervening in NETs is an important approach to treating metabolic diseases. Research has shown a close relationship between the theory of spleen heat-turbid toxin theory and metabolic diseases-NETs mechanism. The basic pathogenesis include the internal accumulation of phlegm-dampness, qi stagnation and blood stasis, internal accumulation of dampness-heat, phlegm and blood stasis, and flourishing toxic heat. Various Chinese herbal medicines with the functions of dispelling dampness, resolving phlegm, promoting blood circulation to remove blood stasis, and clearing heat and toxins, along with their extracts and compound prescriptions, can treat metabolic diseases by regulating NETs and delaying disease progression. This paper systematically outlined the formation mechanisms of NETs, their connection to metabolic diseases, the theoretical basis in TCM, their roles in numerous metabolic diseases, and the current research status of TCM in regulating NETs to prevent and control metabolic diseases, aiming to provide effective reference ideas for developing therapeutic strategies for metabolic diseases.
Humans
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Extracellular Traps/metabolism*
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Metabolic Diseases/metabolism*
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Drugs, Chinese Herbal/therapeutic use*
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Animals
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Neutrophils/metabolism*
;
Medicine, Chinese Traditional
3.Advances in the role and mechanism of tumor-associated neutrophils in gastric cancer.
Yinyin YUAN ; Fangfang LI ; Dongfang LI
Chinese Journal of Cellular and Molecular Immunology 2025;41(2):172-177
Gastric cancer (GC) is a highly prevalent malignant tumor of the digestive system, with high incidences and mortality rates worldwide, posing a serious threat to human health. Studies have shown that tumor-associated neutrophils (TAN) are closely related to adverse biological behaviors of GC, such as initiation, invasion and metastasis, immune evasion, and resistance to treatment, playing a pivotal role in the pathological progression of GC. This article aims to summarize the role of neutrophils in the onset and development of GC and explore their potential applications in GC treatment by reviewing relevant literature in recent years, in order to provide reference for clinicians and basic research.
Humans
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Stomach Neoplasms/therapy*
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Neutrophils/pathology*
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Animals
4.Research progress on the role of macrophages in neutrophilic asthma.
Hongnian LU ; Yuting WU ; Tingting WANG ; Rong GAO ; Weizhen QIAO
Chinese Journal of Cellular and Molecular Immunology 2025;41(9):837-843
Asthma is a chronic inflammatory disease of the airway involving various cellular players. Among the different phenotypes of asthma, neutrophilic asthma is often associated with severe airway inflammation and a notable resistance to corticosteroid treatment. Macrophages, as innate immune cells, play a crucial role in the pathogenesis of neutrophilic asthma. They regulate neutrophil recruitment and activation to promote the progression of airway inflammation. During this process, macrophages also undergo changes in aspects such as efferocytosis. We reviewed the recent research progresses regarding the role of macrophages in the pathogenesis of neutrophilic asthma, aiming to provide valuable insights for future studies in this area.
Humans
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Asthma/pathology*
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Neutrophils/pathology*
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Macrophages/immunology*
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Animals
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Phagocytosis
5.Value of monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in evaluating the severity and prognosis of pediatric viral encephalitis.
Chinese Journal of Contemporary Pediatrics 2025;27(8):968-973
OBJECTIVES:
To investigate the value of peripheral blood monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) in evaluating the severity and prognosis of pediatric viral encephalitis (VE).
METHODS:
A retrospective analysis was performed for the clinical data of 268 children with VE who were admitted to the Department of Pediatrics, Zhucheng People's Hospital, from February 2020 to September 2024. According to the Glasgow Coma Scale (GCS) score, the children were divided into critical group (109 children; GCS score ≤8) and non-critical group (159 children; GCS score >8). According to the results of Glasgow Outcome Scale after follow-up for six months, the children were divided into poor prognosis group (84 children; grade 1-3) and good prognosis group (184 children; grade 4-5). The influencing factors for disease severity and prognosis were analyzed, and the value of peripheral blood MLR and NLR in predicting disease severity and prognosis was assessed.
RESULTS:
The multivariate logistic regression analysis showed that high neutrophil (NEU) count, high MLR, high NLR, and low lymphocyte (LYM) count were closely associated with the critical condition and poor prognosis in children with VE (P<0.05). The receiver operating characteristic curve analysis showed that MLR and NLR had an area under the curve (AUC) of 0.772 and 0.883, respectively, for predicting critical illness in children with VE (P<0.05), as well as an AUC of 0.715 and 0.930, respectively, for predicting poor prognosis (P<0.05).
CONCLUSIONS
Peripheral blood MLR and NLR are associated with critical condition and poor prognosis and can be used as biomarkers for assessing the disease severity and prognosis in children with VE on admission.
Humans
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Prognosis
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Male
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Female
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Child, Preschool
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Child
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Retrospective Studies
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Neutrophils
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Lymphocytes
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Infant
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Encephalitis, Viral/diagnosis*
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Monocytes
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Adolescent
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Logistic Models
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ROC Curve
6.Advancement in neutrophil-based drug delivery systems.
Journal of Zhejiang University. Medical sciences 2025;54(4):479-488
Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans
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Drug Delivery Systems/methods*
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Neutrophils
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Phagocytosis
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Drug Carriers
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Blood-Brain Barrier
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Neoplasms/drug therapy*
7.Research Progress of Tumor-associated Neutrophils in the Occurrence and Development of Lung Cancer.
Xiaoyan LI ; Jianjun ZHOU ; Chaoting ZHAO ; Yudi ZHANG
Chinese Journal of Lung Cancer 2025;28(1):55-62
Lung cancer is the malignant tumor with the highest mortality rate worldwide. The tumor microenvironment (TME) is a key factor in the progression of lung cancer, composed of tumor cells, signaling molecules, fibroblasts, immune cells, etc. Among them, tumor associated neutrophil (TAN), as an important component of immune cells in the TME, plays multiple roles in tumor cell proliferation, invasion, angiogenesis, and metastasis due to its aberrant function, and is closely associated with poor prognosis. However, there are limited researches on the mechanism of TAN in lung cancer. This review aims to provide more scientific basis for studying the therapeutic targets of lung cancer and developing new drugs by elucidating the different subtypes of TAN and their mechanisms of action in the occurrence and development of lung cancer.
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Humans
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Neutrophils/pathology*
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Lung Neoplasms/pathology*
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Tumor Microenvironment
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Animals
8.Dual Roles of Neutrophil Extracellular Traps in Lung Cancer: Mechanism Exploration and Therapeutic Prospects.
Chengdao LI ; Dongge PENG ; Wei SUN
Chinese Journal of Lung Cancer 2025;28(1):63-68
Lung cancer is one of the most common and lethal malignancies in China. In the context of the tumor microenvironment, neutrophil extracellular traps (NETs) released by neutrophils exert a profound impact on the occurrence and progression of lung cancer. Although the exact mechanisms by which NETs promote tumor growth have not been fully elucidated, existing research has revealed their multiple roles in tumor growth, invasion, metastasis, and cancer-related thrombosis. This article will review the molecular biology mechanisms and research progress of NETs in lung cancer based on recent studies.
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Extracellular Traps/metabolism*
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Humans
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Lung Neoplasms/drug therapy*
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Neutrophils/immunology*
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Animals
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Tumor Microenvironment
9.Research Progress of Neutrophil Extracellular Traps in Lung Cancer.
Xu HAO ; Yilin FENG ; Anqi LU ; Ying SUN ; Jinchan XIA ; Xue MEI ; Long FENG ; Min JIANG ; Baiyan WANG ; Huitong YANG
Chinese Journal of Lung Cancer 2025;28(3):201-212
Neutrophil extracellular traps (NETs), intricate reticular structures released by activated neutrophils, play a pivotal regulatory role in the pathogenesis of malignant tumors. Lung cancer is one of the most prevalent malignancies globally, with persistently high incidence and mortality rates. Recent studies have revealed that NETs dynamically modulate the tumor microenvironment through unique pathological mechanisms, exhibiting complex immunoregulatory characteristics during the progression of lung cancer, and this discovery has increasingly become a focal point in tumor immunology research. This paper provides a comprehensive review of the latest advancements in NETs research related to lung cancer, offering an in-depth analysis of their impact on lung cancer progression, their potential diagnostic value, and the current state of research on targeting NETs for lung cancer prevention and treatment. The aim is to propose novel strategies to enhance therapeutic outcomes and improve the prognosis for lung cancer patients.
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Extracellular Traps/immunology*
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Humans
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Lung Neoplasms/metabolism*
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Neutrophils/metabolism*
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Animals
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Tumor Microenvironment
10.Joint detection of serum NLR, PSA and MMP26 in differentiating prostate cancer from benign prostatic hyperplasia.
Yi-Jin WANG ; Qiang LI ; Guang-Bo FU
National Journal of Andrology 2025;31(5):421-425
OBJECTIVE:
To explore the application value of joint detection of serum neutrophil-to-lymphocyte ratio (NLR), prostate-specific antigen (PSA) and MMP26 in differentiating prostate cancer (PCa) from benign prostatic hyperplasia (BPH).
METHODS:
A total of 61 PCa patients (PCa group) and 63 BPH patients (BPH group) who were treated in The Affiliated Huaian Hospital of Xuzhou Medical University from May 2022 to May 2024 were retrospectively included. The relevant clinical data of all subjects were collected with the serum NLR, PSA and MMP26 levels being detected. Multivariate logistic regression analysis was used to analyze the influencing factors in differentiating PCa from BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of serum NLR, PSA and MMP26 in differentiating PCa from BPH.
RESULTS:
The levels of TC and LDL-C in the PCa group were higher than those in the BPH group. And the level of HDL-C in the PCa group was lower than that in the BPH group (P<0.05). The serum levels of NLR, PSA and MMP26 in the PCa group were higher than those in the BPH group (P<0.05). The results of multivariate logistic regression analysis showed that NLR, PSA and MMP26 were risk factors for the diagnosis of PCa in patients (P<0.05). The ROC results showed that the area under the curve (AUC) of NLR, PSA MMP26 and joint diagnosis in the identification of PCa was 0.804, 0.800, 0.809 and 0.905, respectively. The comparison results of AUC showed that the joint diagnosis was superior to the single diagnosis (Z=2.262, 2.177, 2.002, P<0.05).
CONCLUSION
The joint detection of serum NLR, PSA and MMP26 has significant application value in the differentiation of PCa and BPH, which is expected to become an effective tool for early screening and diagnosis of PCa.
Humans
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Male
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Prostatic Hyperplasia/blood*
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Prostate-Specific Antigen/blood*
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Diagnosis, Differential
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Prostatic Neoplasms/blood*
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Retrospective Studies
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Neutrophils
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Lymphocytes
;
ROC Curve
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Aged
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Middle Aged

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