In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to elimin...In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohe...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.展开更多
Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as...Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.展开更多
Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent repro...Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.展开更多
Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed t...Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.展开更多
Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell...Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell transcriptomics(scRNA-seq)and spatial transcriptomics(ST)to highlight the pivotal role of tumor-associated neutrophils(TANs)among tumor-infiltrating immune cells and their therapeutic response to MTC.MNDA+TANs with anti-tumor activity(N1-phenotype)are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion,and these TANs are characterized by enhanced cytotoxicity,ameliorated hypoxia,and upregulated IL1B,activating T&NK cells and fibroblasts via IL1B-IL1R.In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC,fibroblasts accumulated in the tumor front(TF)can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs(pro-tumor phenotype)via CXCL12-CXCR4,which results in the aggregation of N1-TANs and extracellular matrix(ECM)deposition.In addition,we construct an N1-TANs marker,MX2,which positively correlates with better prognosis in LSCC patients,and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin(H&E)-stained images so as to conveniently guide decision making in clinical practice.Collectively,our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.展开更多
Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory act...Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory activity,and clearance of neutrophils are strictly regulated to prevent inflammation-induced tissue damage.Inflammation pervades almost every type of cancer.However,there is growing awareness that although the tumor microenvironment has the capacity to recruit neutrophils,the functions are diverse and include roles other than that of sentinels in cancer.This review highlights the heterogeneity of neutrophils in tumors,discusses the dual role of neutrophils as angels and demons in tumorigenesis,invasion,and metastasis,and examines the potential of neutrophils as targets in clinical therapy.展开更多
Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins...Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins released by neutrophils,contribute significantly to both inflammation and thrombosis.This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis,highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD.Notably,the impact of radiation on NET formation is explored,emphasising how oxidative stress and inflammatory responses drive NET release,contributing to plaque instability.The role of histones,particularly citrullinated histones,in endothelial dysfunction and plaque progression is discussed,highlighting their significance in the pathophysiology of atherosclerosis.Furthermore,the complex relationship between lipoproteins and NET formation is examined,with a focus on how elevated low-density lipoprotein(LDL)and decreased high-density lipoprotein(HDL)levels facilitate NET release,thus promoting vascular inflammation and plaque instability.The influence of cholesterol on NET formation is also explored,underscoring its contribution to plaque development and stability.The role of Peptidylarginine deiminase 4(PAD4)in the regulation of NETosis is reviewed,with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression.Moreover,the manuscript examines the potential of NET components—such as double-stranded DNA,myeloperoxidase–DNA complexes,and citrullinated histone H3—as biomarkers for assessing disease severity and predicting adverse cardiovascular events,including ST-elevation myocardial infarction(STEMI)and stroke.Elevated levels of these biomarkers correlate with worse clinical outcomes,suggesting their utility in guiding therapeutic interventions.In contrast to the existing body of work,this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism,histone modifications,and PAD4 activity in the context of atherosclerosis.Overall,NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis,and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.展开更多
Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under s...Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under specific stimuli,including DNA,histones,and a variety of granular proteins.NETs have been widely studied in the fields of infectious and immune diseases,and new break-throughs have been made in the understanding of disease pathogenesis and treatment.In recent years,studies have found that NETs play an important role in the occurrence and development of osteoarticular diseases.This article reviews the progress in the research of NETs in common osteoarticular diseases such as rheumatoid arthritis,ankylosing spondylitis,gouty arthritis,osteonecrosis of the femoral head,osteoarthritis,and joint fibrosis,including the formation mecha-nism of NETs and its role in inflammation,joint destruction,pain and other pa-thological processes.The problems existing in current research are discussed,along with future research directions,to provide a reference for the in-depth study of osteoarticular diseases and the development of new treatment strategies.展开更多
ABSTRACT:Background:After ischemic stroke,neutrophils hyperactivate,increasing in number and worsening inflammation,causing neural damage.Prior scRNA-seq showed Lrg1 modulates cells subsentence to cerebral ischemiarep...ABSTRACT:Background:After ischemic stroke,neutrophils hyperactivate,increasing in number and worsening inflammation,causing neural damage.Prior scRNA-seq showed Lrg1 modulates cells subsentence to cerebral ischemiareperfusion injury,but its mechanism in regulating neutrophil accumulation/differentiation post-injury is unclear.Methods:Lrg1 knockout impact on neutrophil accumulation was assessed via immunofluorescence and western blot.Three-dimensional reconstruction of immunofluorescent staining analyzed cell-cell interactions among neutrophils and microglia.scRNA-seq of WT and Lrg1^(-/-)mice from GSE245386 and GSE279462 was conducted.Each group conducted oxidative phosphorylation scoring via Gene Set Enrichment Analysis(GSEA),while Metascape was employed to perform GO and KEGG enrichment analyses for elucidating functional mechanisms.CellChat exhibited cell-cell communication.Furthermore,alterations in microglial phagocytic activity were evaluated by immunostaining for CD68,a well-established marker of phagolysosomal activity in phagocytic cells.Brain energy metabolism was evaluated via glutamate dehydrogenase activity and ATP levels with ELISA,and enzyme expression was analyzed by immunofluorescence and western blot.Results:Lrg1 knockout decreased neutrophil accumulation and NET formation in mice.3D immunofluorescence reconstruction confirmed neutrophil co-localization with endothelial cells/microglia.scRNA-seq revealed that the oxidative phosphorylation score was significantly higher in the MCAO/R+WT group compared to both the Sham-operated+WT and Lrg1^(-/-)groups.Notably,the oxidative phosphorylation score was further elevated in the MCAO/R+Lrg1^(-/-)group.Immunostaining showed that Lrg1 knockout elevated CD68+lysosome expression post-MCAO/R,with TMEM119 colocalizing with these lysosomes.MCAO/R raised CD68 expression in ischemic brains,an effect further intensified by Lrg1 knockout.KEGG analysis linked differential genes to oxidative phosphorylation pathways.Validation in MCAO/R vs.sham groups revealed increased ROS production and reduced expression of complex enzymes I-V(NDUFB8,SDHB,UQCRC1,MTCO2,ATP5A1).Lrg1 intervention increased enzyme expression.Immunofluorescence and western blot in brain tissue showed similar patterns in microglia and enzymes I-V.Conclusions:Lrg1 knockout significantly enhances microglial phagocytic activity towards neutrophils subsequent to cerebral ischemia-reperfusion injury,through its regulatory effect on the oxidative phosphorylation pathway.This finding accentuates Lrg1 as a highly potential therapeutic target for intervening in and modulating post-ischemic inflammatory responses.展开更多
This study evaluates the findings of Gu et al,who investigated the role of neutrophil gelatinase-associated lipocalin(NGAL)as a biomarker for predicting neuropsychiatric complications in acute ischemic stroke(AIS)pati...This study evaluates the findings of Gu et al,who investigated the role of neutrophil gelatinase-associated lipocalin(NGAL)as a biomarker for predicting neuropsychiatric complications in acute ischemic stroke(AIS)patients.The results revealed that elevated serum NGAL levels at admission are associated with a higher risk of cognitive impairment,anxiety,and depressive symptoms at discharge.The study analyzed 150 AIS patients(mean age 65.4 years,58%male)using the Mini-Mental State Examination and the Hospital Anxiety and Depression Scale to assess neuropsychiatric outcomes.Multivariate analysis demonstrated that higher NGAL levels were independent predictors of cognitive impairment[odds ratio(OR)=1.42],anxiety(OR=1.28),and depression(OR=1.39).Notably,NGAL exhibited strong predictive power for cognitive impairment,with an area under the curve of 0.78.Despite these promising findings,NGAL’s clinical utility is limited by its non-specificity across various conditions.Nevertheless,NGAL levels could help identify AIS patients at risk for neuropsychiatric complications,enabling timely intervention and comprehensive neuropsychiatric evaluation.The study emphasizes the need for further research to validate NGAL’s predictive accuracy and specificity in diverse AIS populations and advocates for its integration with other diagnostic modalities to enhance clinical decision-making.展开更多
BACKGROUND Osteoarthritis(OA)involves low-grade inflammation.The neutrophil-to-lym-phocyte ratio(NLR)may serve as a simple biomarker,but its role in OA remains unclear.AIM To review the existing scientific literature ...BACKGROUND Osteoarthritis(OA)involves low-grade inflammation.The neutrophil-to-lym-phocyte ratio(NLR)may serve as a simple biomarker,but its role in OA remains unclear.AIM To review the existing scientific literature on the role of NLR in OA,a classic age-related disorder,to perform a meta-analysis of the available data.METHODS The electronic databases PubMed,ProQuest,and Scopus were systematically searched from inception to March 1,2024.The inclusion criteria were retro-spective and prospective case-control studies involving human subjects with OA and healthy controls.The included studies needed to provide NLR levels for both OA patients and healthy controls and perform a comparative analysis of NLR levels between these groups.RESULTS According to the PRISMA guidelines,fifteen articles were included in the meta-analysis after multiple screenings.The pooled results demonstrated a significant overall elevation of NLR in OA patients compared to healthy controls.(standardized mean difference=0.39,95%confidence interval:0.03-0.75,P=0.03).However,the subgroup analysis shows no significant differences in NLR levels when considering study design(retrospective vs prospective)and OA severity(severe vs mild-moderate).This suggests variability and potential limitations in using NLR as a consistent marker across different study types and OA severity.CONCLUSION Our study found that OA patients have higher NLR than healthy individuals.However,NLR did not significantly differ by study type or disease severity,suggesting its limited use in indicating OA severity.展开更多
BACKGROUND Gastric cancer(GC)is a leading cause of cancer-related mortality worldwide,with Helicobacter pylori(H.pylori)infection recognized as a major risk factor.Chronic H.pylori-induced inflammation drives carcinog...BACKGROUND Gastric cancer(GC)is a leading cause of cancer-related mortality worldwide,with Helicobacter pylori(H.pylori)infection recognized as a major risk factor.Chronic H.pylori-induced inflammation drives carcinogenesis through neutrophilmediated pathways,in which cytokine-induced neutrophil chemoattractant(CINC)plays a pivotal role.However,the interplay among H.pylori virulence factors,systemic CINC levels,and GC progression remains poorly defined.AIM To investigate the correlation among serum CINC levels,H.pylori infection,and disease severity in patients with GC.METHODS This retrospective cohort study included 258 patients with GC diagnosed between April 2020 and November 2023.H.pylori infection was confirmed via histology,rapid urease test,and serology.Serum CINC levels were quantified using ELISA.Statistical analyses were performed with SPSS 26.0.RESULTS The H.pylori-positive patients exhibited significantly higher serum CINC levels(312.5±120.3 pg/mL)than the H.pylori-negative patients(150.2±95.4 pg/mL;P<0.05).CINC levels were correlated positively with TNM stage in the H.pyloripositive patients(P<0.05),with the highest levels recorded in stage IV(415.7±150.6 pg/mL).The patients infected with cytotoxin-associated gene A/vacuolating cytotoxin-positive H.pylori strains had elevated CINC levels(P<0.05).High CINC levels and H.pylori infection independently predicted poor survival CONCLUSION Elevated serum CINC levels are strongly associated with H.pylori infection,advanced TNM staging,and poor prognosis in GC.CINC serves as a novel prognostic biomarker,underscoring the role of neutrophil-driven inflammation in H.pylori-associated carcinogenesis.展开更多
Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pa...Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.展开更多
The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall hea...The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall health.Studies have demonstrated a significant association between aging and the dysfunction of neutrophils,critical cells in the early stages of periodontitis,and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion.Neutrophils differentiate and mature in the bone marrow before entering the circulation;during an infection,they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens.Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues.The impacts of aging on neutrophils'chemotaxis,anti-microbial function,cell activation,and lifespan result in impaired neutrophil functions and excessive neutrophil activation,which could influence periodontitis course.We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses.We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging.This review could help us better understand the pathogenesis of periodontitis,which could offer novel therapeutic targets for periodontitis.展开更多
Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have r...Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.展开更多
BACKGROUND Acute kidney injury(AKI)is a severe complication of acute pancreatitis(AP)associated with increased morbidity and mortality.Early prediction of AKI remains a clinical challenge owing to the limitations of t...BACKGROUND Acute kidney injury(AKI)is a severe complication of acute pancreatitis(AP)associated with increased morbidity and mortality.Early prediction of AKI remains a clinical challenge owing to the limitations of traditional biomarkers,such as serum creatinine.AIM To evaluate the concentration and predictive value of plasma neutrophil gelatinase-associated lipocalin(NGAL)in patients with AP and AKI.METHODS This cross-sectional descriptive study was conducted from October 2021 to June 2023 at Bach Mai Hospital.In total,219 patients were enrolled,including 51 patients with AP and AKI,168 patients with AP but without AKI,and 35 healthy controls.Plasma NGAL levels were measured and compared between groups.Receiver operating characteristic curve analysis was performed to determine the predictive value of NGAL levels for the severity of AKI and AP.RESULTS Among AP and AKI cases,47.1%were classified as Kidney Disease:Improving Global Outcomes stage 1,33.3%as stage 2,and 19.6%as stage 3.The AP with AKI group(570.9 ng/mL)had significantly higher median plasma NGAL concentrations than the AP without AKI group(400.6 ng/mL)and the healthy control group(234.3 ng/mL)(P<0.01).The NGAL levels increased proportionally with AKI severity.A plasma NGAL cutoff value of 504.29 ng/mL predicted AKI with 60.8%sensitivity and 68.4%specificity(area under the curve=0.684;P<0.001).A cutoff of 486.03 ng/mL predicted AP severity with 66.1%sensitivity and 66.4%specificity(area under the curve=0.651;P<0.005).NGAL positively correlated with international normalized ratio,urea,creatinine,lactate dehydrogenase,and lactate levels.CONCLUSION Plasma NGAL levels predicted both AKI development and disease severity.Therefore,NGAL should be considered a useful biomarker for the early evaluation of patients with AP.展开更多
Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.Mo...Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.More effective medical interventions,including those involving traditional Chinese medicine,could be beneficial for patients with newly diagnosed colorectal cancer to prevent the progression to liver metastasis.Xiaoyaosan(XYS)is a classical prescription in traditional Chinese medicine with a history of hundreds of years.Despite its well-known protective effects against breast cancer,the understanding of its application in colorectal cancer metastases remains limited.The anti-metastasis mechanism of XYS remains to be elucidated.In this research,we explored the impact of XYS against liver metastases of colorectal cancer and its potential mechanisms.Methods:Thirty-six SPF male C57BL/6 mice were randomly assigned to six groups:a control group,a model group,a DNase I group,and three XYS treatment groups receiving high,medium,and low doses,respectively.A mouse model for colorectal cancer liver metastasis was established through the splenic injection of MC38 cells.Twenty-one days after the injection of cancer cells,the number of metastatic foci and the weights of the liver were calculated,and HE staining was performed to evaluate the effect of XYS.Neutrophil extracellular traps(NETs)formation in the liver was detected by immunofluorescence staining,and NETs formation in the serum was detected by ELISA.The levels of CXCL1,CXCL2,G-CSF,and HMGB1 were determined using ELISA kits.The expression levels of the proteins p-p38,p38,p-ERK,and ERK were assessed using Western blot analysis.Results:XYS treatment reduced the number of metastatic foci,the weights of metastatic livers,and the infiltration area of tumor-like cells.XYS could inhibit NETs formation in the liver and serum of mice with metastasis.The concentrations of CXCL1,CXCL2,G-CSF,and HMGB1 were significantly decreased in all XYS-treated groups.Moreover,XYS down-regulated the protein expression levels of phosphorylated p38 and ERK.Conclusion:XYS could attenuate liver metastases of colorectal cancer in vivo.The inhibitory mechanism of XYS may involve the reduction of NETs formation through the regulation of tumor-derived factors and the downstream MAPKs(p38,ERK)signaling pathway.展开更多
Neutrophils are the first immune responders to infection.Th ey rapidly migrate to the site of infection and phagocytose pathogens.Additionally,they release neutrophil extracellular traps(NETs)to immobilize and kill pa...Neutrophils are the first immune responders to infection.Th ey rapidly migrate to the site of infection and phagocytose pathogens.Additionally,they release neutrophil extracellular traps(NETs)to immobilize and kill pathogens via a unique form of cell death known as netosis[1,2].Recently,a groundbreaking study published in Nature reported that a subgroup of neutrophils contributes to the composition and structure of the extracellular matrix(ECM),reinforces its mechanical properties,and promotes its barrier function in both naive and wounded skin[3].The structural and functional contributions of these neutrophils support those of“professional”ECM producers(e.g.,fibroblasts)in a non-redundant manner by locally modulating the dynamics of the ECM in the skin.展开更多
Despite suggested shared pathophysiological mechanisms between coronavirus disease 2019(COVID-19)and multiple sclerosis(MS),the molecular pathways underlying their relationship remain unclear.Herein,gene expression pr...Despite suggested shared pathophysiological mechanisms between coronavirus disease 2019(COVID-19)and multiple sclerosis(MS),the molecular pathways underlying their relationship remain unclear.Herein,gene expression profiles of COVID-19(GSE171110,GSE152641)and MS(GSE66573,GSE159225)datasets were analyzed using Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and protein-protein interaction(PPI)network construction.A two-acsample Mendelian randomization(MR)study was performed to establish potential causal relationships.A total of 165 shared differentially expressed genes(DEGs)were identified,with significant enrichment in pathways related to humoral immune response,neutrophil migration,and cytokine-receptor interactions in both conditions.Validation by receiver operating characteristic(ROC)curve analysis demonstrated that the hub genes S100A8,S100A9,S100A12,and ALOX5AP achieved area under the curve(AUC)values above 0.7 for both diseases.Increased neutrophil infiltration was positively correlated with upregulated expression of these genes,particularly demonstrating significant associations between the hub gene expression and neutrophil activity pathways.MR analysis suggested a causal relationship between S100A8 expression and susceptibility to both conditions and neutrophil counts,while ALOX5AP was indicated as a potential MS risk factor.These findings suggest that COVID-19 and MS co-occurrence is associated with neutrophil infiltration,highlighting S100A8 as both a promising biomarker and therapeutic target.展开更多
文摘In this article,we make a comment on the recent article by Sun et al,focusing on the advances of neutrophil extracellular traps(NETs)formation in common osteoarticular diseases.Neutrophils are the first line to eliminate invading pathogens including fungal and bacterial infections via releasing hydrolytic enzymes and reactive oxygen species.Besides,neutrophils will accumulate at the inflammatory site and release NETs,which are composed of histones,DNA and granular proteins.Traumatic heterotopic ossification(THO)was generally believed to develop through four stages:Inflammation,chondrogenesis,osteogenesis,and bone maturation.Thus,it can be seen that THO was related to inflammation and bone formation.Apart from immune and infectious diseases,recent studies have also shown that NETs play a significant role in the pathogenesis of THO.This article focuses on elaborating the role of NETs in the onset of THO,discussing the existing problems in the current research and outlining future directions.
基金Supported by Slovak Research and Development Agency,No.APVV-21-0370Ministry of Education,Science,Research and Sport of the Slovak Republic,No.VEGA 1/0706/25 and No.VEGA 1/0341/23.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a prevalent chronic liver disorder driven by obesity and metabolic dysfunction.MASLD progresses to metabolic dysfunction-associated steatohepatitis,which is characterized by inflammation,hepatocyte injury,and fibrosis,increasing the risk of cirrhosis and liver failure.Recent studies suggest that neutrophil extracellular traps(NETs)and extracellular DNA(ecDNA)contribute to liver inflammation and fibrogenesis.However,their role in MASLD pathogenesis remains incompletely understood.AIM To investigate the dynamics of circulating NETs and ecDNA as potential biomarkers of liver injury in MASLD.METHODS Using three complementary mouse models,thioacetamide(TAA)-induced fibrosis,choline-deficient L-amino acid-defined(CDAA)diet-induced metabolic dysfunction-associated steatohepatitis,and cafeteria(CAF)diet-induced MASLD,we assessed the association between NET-related markers and liver damage.Blood samples were collected biweekly to analyze ecDNA and NET markers,including myeloperoxidase(MPO)and MPO-DNA complexes,using ELISA and real-time PCR.Liver histopathology was assessed for inflammation,fibrosis,and neutrophil infiltration.RESULTS The TAA and CDAA models exhibited significant liver injury,characterized by increased plasma alanine aminotransferase and aspartate aminotransferase levels,hepatocellular damage,and fibrosis.Elevated circulating NET markers(MPO and ecDNA)were observed in these models,with a strong correlation between NET formation and liver pathology.The CAF diet model induced steatosis but failed to elicit significant liver fibrosis or an increase in NET markers,suggesting that NETosis is associated with more severe liver damage.Notably,ecDNA and MPO levels correlated with neutrophil infiltration and fibrosis scores,indicating their potential as biomarkers of MASLD progression.CONCLUSION NETosis and ecDNA levels reflect liver injury severity in MASLD.NET markers and liver fibrosis were strongly associated in TAA and CDAA models,whereas CAF model showed minimal NET involvement.
基金supported by the National Natural Science Foundation of China(Grant nos.82473157,82460510,82203565,82103388,31960145 and 82560591)the Natural Science Foundation of Beijing(Grant no.L248059)+1 种基金Yunnan Province applied research funds(Grant nos.202201AY070001-011,202201AY070001-043,and 202301AS070018)the Science and Technology Innovation Team of tumor metabolism research at Kunming Medical University(Grant no.CXTD202102).
文摘Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.
基金funded by grants from the National Natural Science Foundation of China(Grant Nos.82373263 and 82403835)the National Key Research and Development Program of China(Grant No.2023YFC2506400)+2 种基金China Postdoctoral Science Foundation(Grant No.2024M751405)Jiangsu Provincial Natural Science Foundation Youth Project(Grant No.BK20240247)General Project of Nanjing Health Science and Technology Development Program(Grant No.YKK24084).
文摘Tumor-associated neutrophils(TANs)exhibit highly func-tional heterogeneity across cancers.Although TANs pro-mote inflammatory responses and contribute to tumor clearance,they frequently undergo context-dependent reprogramming within the tumor microenvironment(TME)into highly immunosuppressive phenotypes that facilitate cancer dissemination and immunotherapy resist-ance1,2.We contend that an underappreciated,upstream determinant of this divergence is the maturation stage of TANs3,4.The developmental stage of TANs determines the migration patterns and constrains the functional capacity,and the developmental stage also constrains the extent of TME-driven re-education,together shaping pro-or anti-tu-mor outcomes3-5.In this Perspective,we place maturation at the core of TAN biology and discuss current definitions for TAN developmental stages and the measurable mark-ers that researchers and clinicians can use(Figure 1).In addition,spatial and temporal transitions in TAN matu-ration stages and the factors that govern these transitions are elucidated.We explain how maturation status shapes TAN function and articulate the key differences between mouse and human TAN maturation systems to highlight the value of human immune system(HIS)mouse models.Based on this framework,functional biomarkers and signa-tures of TAN maturation are introduced and we show how to embed them into patient stratification and longitudinal monitoring.Finally,we outline immunotherapy strategies targeting TAN maturation,selecting interventions guided by maturation markers to reinforce treatment benefits for cancer patients.
基金the support of the National Natural Science Foundation of China (Grant No.82272503)Natural Science Foundation of Zhejiang Province (Grant No. LQN25H060006)
文摘Exosomes have shown good potential in ischemic injury disease treatments.However,evidence about their effect and molecular mechanisms in osteonecrosis of femoral head(ONFH)treatment is still limited.Here,we revealed the cell biology characters of ONFH osteonecrosis area bone tissue in single cell scale and thus identified a novel ONFH treatment approach based on M2 macrophages-derived exosomes(M2-Exos).We further show that M2-Exos are highly effective in the treatment of ONFH by modulating the phenotypes communication between neutrophil and endothelium including neutrophil extracellular traps formation and endothelial phenotype transition.Additionally,we identified that M2-Exos’therapeutic effect is attributed to the high content of miR-93-5p and constructed miR-93-5p overexpression model in vitro and in vivo based on lentivirus and adenoassociated virus respectively.Then we found miR-93-5p can not only reduce neutrophil extracellular traps formation but also improve angiogenic ability of endothelial cells.These results provided a new theoretical basis for the clinical application of ONFH therapeutic exosomes.
基金supported by National Natural Science Foundation of China grants(Nos.82173326 and 82473058)Key Research and Development Project of Sichuan Province(Nos.2024YFFK0374 and 2024YFFK0198)Interdisciplinary Innovation Project of West China College of Stomatology,Sichuan University(RD-03-202004).
文摘Microwave thermochemotherapy(MTC)has been applied to treat lip squamous cell carcinoma(LSCC),but a deeper understanding of its therapeutic mechanisms and molecular biology is needed.To address this,we used single-cell transcriptomics(scRNA-seq)and spatial transcriptomics(ST)to highlight the pivotal role of tumor-associated neutrophils(TANs)among tumor-infiltrating immune cells and their therapeutic response to MTC.MNDA+TANs with anti-tumor activity(N1-phenotype)are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion,and these TANs are characterized by enhanced cytotoxicity,ameliorated hypoxia,and upregulated IL1B,activating T&NK cells and fibroblasts via IL1B-IL1R.In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC,fibroblasts accumulated in the tumor front(TF)can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs(pro-tumor phenotype)via CXCL12-CXCR4,which results in the aggregation of N1-TANs and extracellular matrix(ECM)deposition.In addition,we construct an N1-TANs marker,MX2,which positively correlates with better prognosis in LSCC patients,and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin(H&E)-stained images so as to conveniently guide decision making in clinical practice.Collectively,our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82273449 and 82203663)the Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ23H160013)the Medical and Health Science and Technology Project of Zhejiang Province(Grant Nos.2024KY1039 and 2024KY1250).
文摘Neutrophils are the protagonists of the host immune response,possessing potent antimicrobial and inflammatory capacities.The neutrophil reservoir as well as the development,mobilization,chemotaxis,pro-inflammatory activity,and clearance of neutrophils are strictly regulated to prevent inflammation-induced tissue damage.Inflammation pervades almost every type of cancer.However,there is growing awareness that although the tumor microenvironment has the capacity to recruit neutrophils,the functions are diverse and include roles other than that of sentinels in cancer.This review highlights the heterogeneity of neutrophils in tumors,discusses the dual role of neutrophils as angels and demons in tumorigenesis,invasion,and metastasis,and examines the potential of neutrophils as targets in clinical therapy.
基金supported by NIH grants to MI Bukrinsky(R01NS124477 and P30AI117970)by the“Creation of Experimental Laboratories in the Natural Sciences Program”and Basic Research Programat Higher School of Economics University.
文摘Neutrophil extracellular traps(NET)have emerged as critical players in the pathogenesis of atherosclerosis and other cardiovascular diseases(CVD).These web-like structures,composed of DNA,histones,and granule proteins released by neutrophils,contribute significantly to both inflammation and thrombosis.This manuscript offers a comprehensive review of the recent literature on the involvement of NET in atherosclerosis,highlighting their interactions with various pathophysiological processes and their potential as biomarkers for CVD.Notably,the impact of radiation on NET formation is explored,emphasising how oxidative stress and inflammatory responses drive NET release,contributing to plaque instability.The role of histones,particularly citrullinated histones,in endothelial dysfunction and plaque progression is discussed,highlighting their significance in the pathophysiology of atherosclerosis.Furthermore,the complex relationship between lipoproteins and NET formation is examined,with a focus on how elevated low-density lipoprotein(LDL)and decreased high-density lipoprotein(HDL)levels facilitate NET release,thus promoting vascular inflammation and plaque instability.The influence of cholesterol on NET formation is also explored,underscoring its contribution to plaque development and stability.The role of Peptidylarginine deiminase 4(PAD4)in the regulation of NETosis is reviewed,with attention given to how PAD4-driven citrullination of histones affects atherosclerosis progression.Moreover,the manuscript examines the potential of NET components—such as double-stranded DNA,myeloperoxidase–DNA complexes,and citrullinated histone H3—as biomarkers for assessing disease severity and predicting adverse cardiovascular events,including ST-elevation myocardial infarction(STEMI)and stroke.Elevated levels of these biomarkers correlate with worse clinical outcomes,suggesting their utility in guiding therapeutic interventions.In contrast to the existing body of work,this review highlights the novelty of integrating recent findings on NET interactions with lipid metabolism,histone modifications,and PAD4 activity in the context of atherosclerosis.Overall,NET plays an integral role in the inflammatory and thrombotic processes underpinning atherosclerosis,and their components hold promise as both diagnostic markers and therapeutic targets in cardiovascular disease management.
基金Supported by 2024 Suining Health Science and Technology Plan Project,No.24ZDJB03.
文摘Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under specific stimuli,including DNA,histones,and a variety of granular proteins.NETs have been widely studied in the fields of infectious and immune diseases,and new break-throughs have been made in the understanding of disease pathogenesis and treatment.In recent years,studies have found that NETs play an important role in the occurrence and development of osteoarticular diseases.This article reviews the progress in the research of NETs in common osteoarticular diseases such as rheumatoid arthritis,ankylosing spondylitis,gouty arthritis,osteonecrosis of the femoral head,osteoarthritis,and joint fibrosis,including the formation mecha-nism of NETs and its role in inflammation,joint destruction,pain and other pa-thological processes.The problems existing in current research are discussed,along with future research directions,to provide a reference for the in-depth study of osteoarticular diseases and the development of new treatment strategies.
基金supported by the Foundation Project:National Natural Science Foundation of China(Nos.:82460249,82100417,81760094)The Foundation of Jiangxi Provincial Department of Science and Technology Outstanding Youth Fund Project(20242BAB23080).
文摘ABSTRACT:Background:After ischemic stroke,neutrophils hyperactivate,increasing in number and worsening inflammation,causing neural damage.Prior scRNA-seq showed Lrg1 modulates cells subsentence to cerebral ischemiareperfusion injury,but its mechanism in regulating neutrophil accumulation/differentiation post-injury is unclear.Methods:Lrg1 knockout impact on neutrophil accumulation was assessed via immunofluorescence and western blot.Three-dimensional reconstruction of immunofluorescent staining analyzed cell-cell interactions among neutrophils and microglia.scRNA-seq of WT and Lrg1^(-/-)mice from GSE245386 and GSE279462 was conducted.Each group conducted oxidative phosphorylation scoring via Gene Set Enrichment Analysis(GSEA),while Metascape was employed to perform GO and KEGG enrichment analyses for elucidating functional mechanisms.CellChat exhibited cell-cell communication.Furthermore,alterations in microglial phagocytic activity were evaluated by immunostaining for CD68,a well-established marker of phagolysosomal activity in phagocytic cells.Brain energy metabolism was evaluated via glutamate dehydrogenase activity and ATP levels with ELISA,and enzyme expression was analyzed by immunofluorescence and western blot.Results:Lrg1 knockout decreased neutrophil accumulation and NET formation in mice.3D immunofluorescence reconstruction confirmed neutrophil co-localization with endothelial cells/microglia.scRNA-seq revealed that the oxidative phosphorylation score was significantly higher in the MCAO/R+WT group compared to both the Sham-operated+WT and Lrg1^(-/-)groups.Notably,the oxidative phosphorylation score was further elevated in the MCAO/R+Lrg1^(-/-)group.Immunostaining showed that Lrg1 knockout elevated CD68+lysosome expression post-MCAO/R,with TMEM119 colocalizing with these lysosomes.MCAO/R raised CD68 expression in ischemic brains,an effect further intensified by Lrg1 knockout.KEGG analysis linked differential genes to oxidative phosphorylation pathways.Validation in MCAO/R vs.sham groups revealed increased ROS production and reduced expression of complex enzymes I-V(NDUFB8,SDHB,UQCRC1,MTCO2,ATP5A1).Lrg1 intervention increased enzyme expression.Immunofluorescence and western blot in brain tissue showed similar patterns in microglia and enzymes I-V.Conclusions:Lrg1 knockout significantly enhances microglial phagocytic activity towards neutrophils subsequent to cerebral ischemia-reperfusion injury,through its regulatory effect on the oxidative phosphorylation pathway.This finding accentuates Lrg1 as a highly potential therapeutic target for intervening in and modulating post-ischemic inflammatory responses.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea Funded by the Ministry of Education,No.RS-2023-00237287Regional Innovation Strategy Through the National Research Foundation of Korea Funded by the Ministry of Education,No.2021RIS-003.
文摘This study evaluates the findings of Gu et al,who investigated the role of neutrophil gelatinase-associated lipocalin(NGAL)as a biomarker for predicting neuropsychiatric complications in acute ischemic stroke(AIS)patients.The results revealed that elevated serum NGAL levels at admission are associated with a higher risk of cognitive impairment,anxiety,and depressive symptoms at discharge.The study analyzed 150 AIS patients(mean age 65.4 years,58%male)using the Mini-Mental State Examination and the Hospital Anxiety and Depression Scale to assess neuropsychiatric outcomes.Multivariate analysis demonstrated that higher NGAL levels were independent predictors of cognitive impairment[odds ratio(OR)=1.42],anxiety(OR=1.28),and depression(OR=1.39).Notably,NGAL exhibited strong predictive power for cognitive impairment,with an area under the curve of 0.78.Despite these promising findings,NGAL’s clinical utility is limited by its non-specificity across various conditions.Nevertheless,NGAL levels could help identify AIS patients at risk for neuropsychiatric complications,enabling timely intervention and comprehensive neuropsychiatric evaluation.The study emphasizes the need for further research to validate NGAL’s predictive accuracy and specificity in diverse AIS populations and advocates for its integration with other diagnostic modalities to enhance clinical decision-making.
文摘BACKGROUND Osteoarthritis(OA)involves low-grade inflammation.The neutrophil-to-lym-phocyte ratio(NLR)may serve as a simple biomarker,but its role in OA remains unclear.AIM To review the existing scientific literature on the role of NLR in OA,a classic age-related disorder,to perform a meta-analysis of the available data.METHODS The electronic databases PubMed,ProQuest,and Scopus were systematically searched from inception to March 1,2024.The inclusion criteria were retro-spective and prospective case-control studies involving human subjects with OA and healthy controls.The included studies needed to provide NLR levels for both OA patients and healthy controls and perform a comparative analysis of NLR levels between these groups.RESULTS According to the PRISMA guidelines,fifteen articles were included in the meta-analysis after multiple screenings.The pooled results demonstrated a significant overall elevation of NLR in OA patients compared to healthy controls.(standardized mean difference=0.39,95%confidence interval:0.03-0.75,P=0.03).However,the subgroup analysis shows no significant differences in NLR levels when considering study design(retrospective vs prospective)and OA severity(severe vs mild-moderate).This suggests variability and potential limitations in using NLR as a consistent marker across different study types and OA severity.CONCLUSION Our study found that OA patients have higher NLR than healthy individuals.However,NLR did not significantly differ by study type or disease severity,suggesting its limited use in indicating OA severity.
基金Supported by Hebei Province Medical Science Research Project Plan,No.20210923.
文摘BACKGROUND Gastric cancer(GC)is a leading cause of cancer-related mortality worldwide,with Helicobacter pylori(H.pylori)infection recognized as a major risk factor.Chronic H.pylori-induced inflammation drives carcinogenesis through neutrophilmediated pathways,in which cytokine-induced neutrophil chemoattractant(CINC)plays a pivotal role.However,the interplay among H.pylori virulence factors,systemic CINC levels,and GC progression remains poorly defined.AIM To investigate the correlation among serum CINC levels,H.pylori infection,and disease severity in patients with GC.METHODS This retrospective cohort study included 258 patients with GC diagnosed between April 2020 and November 2023.H.pylori infection was confirmed via histology,rapid urease test,and serology.Serum CINC levels were quantified using ELISA.Statistical analyses were performed with SPSS 26.0.RESULTS The H.pylori-positive patients exhibited significantly higher serum CINC levels(312.5±120.3 pg/mL)than the H.pylori-negative patients(150.2±95.4 pg/mL;P<0.05).CINC levels were correlated positively with TNM stage in the H.pyloripositive patients(P<0.05),with the highest levels recorded in stage IV(415.7±150.6 pg/mL).The patients infected with cytotoxin-associated gene A/vacuolating cytotoxin-positive H.pylori strains had elevated CINC levels(P<0.05).High CINC levels and H.pylori infection independently predicted poor survival CONCLUSION Elevated serum CINC levels are strongly associated with H.pylori infection,advanced TNM staging,and poor prognosis in GC.CINC serves as a novel prognostic biomarker,underscoring the role of neutrophil-driven inflammation in H.pylori-associated carcinogenesis.
基金supported by Beijing Natural Science Foundation(Grant No.Z210014)National Natural Science Foundation of China(Grant No.32070543)+1 种基金National Key Research and Development Project of China(Grant No.2022YFC2303404)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-12M-CoV19-002)
文摘Background:SARS-CoV-2,first identified in late 2019,has given rise to numerous variants of concern(VOCs),posing a significant threat to human health.The emer-gence of Omicron BA.1.1 towards the end of 2021 led to a pandemic in early 2022.At present,the lethal mouse model for the study of SARS-CoV-2 needs supplementation,and the alterations in neutrophils and monocytes caused by different strains remain to be elucidated.Methods:Human ACE2 transgenic mice were inoculated with the SARS-CoV-2 proto-type and Omicron BA.1,respectively.The pathogenicity of the two strains was evalu-ated by observing clinical symptoms,viral load and pathology.Complete blood count,immunohistochemistry and flow cytometry were performed to detect the alterations of neutrophils and monocytes caused by the two strains.Results:Our findings revealed that Omicron BA.1 exhibited significantly lower vir-ulence compared to the SARS-CoV-2 prototype in the mouse model.Additionally,we observed a significant increase in the proportion of neutrophils late in infection with the SARS-CoV-2 prototype and Omicron BA.1.We found that the proportion of monocytes increased at first and then decreased.The trends in the changes in the proportions of neutrophils and monocytes induced by the two strains were similar.Conclusion:Our study provides valuable insights into the utility of mouse models for simulating the severe disease of SARS-CoV-2 prototype infection and the milder manifestation associated with Omicron BA.1.SARS-CoV-2 prototype and Omicron BA.1 resulted in similar trends in the changes in neutrophils and monocytes.
文摘The increasing aging population and aging-associated diseases have become a global issue for decades.People over 65 show an increased prevalence and greater severity of periodontitis,which poses threats to overall health.Studies have demonstrated a significant association between aging and the dysfunction of neutrophils,critical cells in the early stages of periodontitis,and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion.Neutrophils differentiate and mature in the bone marrow before entering the circulation;during an infection,they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens.Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues.The impacts of aging on neutrophils'chemotaxis,anti-microbial function,cell activation,and lifespan result in impaired neutrophil functions and excessive neutrophil activation,which could influence periodontitis course.We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses.We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging.This review could help us better understand the pathogenesis of periodontitis,which could offer novel therapeutic targets for periodontitis.
基金the Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Yantai Science and Technology Program,No.2024YD005,No.2024YD007 and No.2024YD010and Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘Colorectal cancer(CRC)is a common malignant tumor worldwide,and its tumor microenvironment(TME)plays a crucial role in tumor progression.Neutrophil extracellular traps(NETs),as an important component of the TME,have received widespread attention in recent years.This article explores the biological functions and molecular mechanisms of NETs in CRC and their impact on disease progression,while analyzing the application of single-cell sequencing technology(SCS)in this field.The development of SCS provides a new perspective for understanding the role of NETs in CRC.By combining SCS technology,targeting key regulatory nodes of NETs is expected to reverse the immunosuppressive microenvironment and provide a theoretical basis for developing novel diagnostic biomarkers and targeted therapeutic strategies,thereby promoting the development of precision medicine in CRC and helping enhance patient prognosis.Future research should further explore the integration of SCS technology with complementary methodologies to investigate NETs and develop specific detection methods and therapeutic strategies targeting NETs to enhance early diagnosis and treatment efficacy of tumors.
文摘BACKGROUND Acute kidney injury(AKI)is a severe complication of acute pancreatitis(AP)associated with increased morbidity and mortality.Early prediction of AKI remains a clinical challenge owing to the limitations of traditional biomarkers,such as serum creatinine.AIM To evaluate the concentration and predictive value of plasma neutrophil gelatinase-associated lipocalin(NGAL)in patients with AP and AKI.METHODS This cross-sectional descriptive study was conducted from October 2021 to June 2023 at Bach Mai Hospital.In total,219 patients were enrolled,including 51 patients with AP and AKI,168 patients with AP but without AKI,and 35 healthy controls.Plasma NGAL levels were measured and compared between groups.Receiver operating characteristic curve analysis was performed to determine the predictive value of NGAL levels for the severity of AKI and AP.RESULTS Among AP and AKI cases,47.1%were classified as Kidney Disease:Improving Global Outcomes stage 1,33.3%as stage 2,and 19.6%as stage 3.The AP with AKI group(570.9 ng/mL)had significantly higher median plasma NGAL concentrations than the AP without AKI group(400.6 ng/mL)and the healthy control group(234.3 ng/mL)(P<0.01).The NGAL levels increased proportionally with AKI severity.A plasma NGAL cutoff value of 504.29 ng/mL predicted AKI with 60.8%sensitivity and 68.4%specificity(area under the curve=0.684;P<0.001).A cutoff of 486.03 ng/mL predicted AP severity with 66.1%sensitivity and 66.4%specificity(area under the curve=0.651;P<0.005).NGAL positively correlated with international normalized ratio,urea,creatinine,lactate dehydrogenase,and lactate levels.CONCLUSION Plasma NGAL levels predicted both AKI development and disease severity.Therefore,NGAL should be considered a useful biomarker for the early evaluation of patients with AP.
基金supported by Sichuan Science and Technology Program(grant number 2023NSFSC1809)Hospital of Chengdu University of Traditional Chinese Medicine(grant number 23ZYTS1004,21YY01).
文摘Background:Liver metastases are a leading contributor to death among patients with colorectal cancer.Current clinical treatments,such as resection and systemic chemotherapy,are only applicable in a portion of cases.More effective medical interventions,including those involving traditional Chinese medicine,could be beneficial for patients with newly diagnosed colorectal cancer to prevent the progression to liver metastasis.Xiaoyaosan(XYS)is a classical prescription in traditional Chinese medicine with a history of hundreds of years.Despite its well-known protective effects against breast cancer,the understanding of its application in colorectal cancer metastases remains limited.The anti-metastasis mechanism of XYS remains to be elucidated.In this research,we explored the impact of XYS against liver metastases of colorectal cancer and its potential mechanisms.Methods:Thirty-six SPF male C57BL/6 mice were randomly assigned to six groups:a control group,a model group,a DNase I group,and three XYS treatment groups receiving high,medium,and low doses,respectively.A mouse model for colorectal cancer liver metastasis was established through the splenic injection of MC38 cells.Twenty-one days after the injection of cancer cells,the number of metastatic foci and the weights of the liver were calculated,and HE staining was performed to evaluate the effect of XYS.Neutrophil extracellular traps(NETs)formation in the liver was detected by immunofluorescence staining,and NETs formation in the serum was detected by ELISA.The levels of CXCL1,CXCL2,G-CSF,and HMGB1 were determined using ELISA kits.The expression levels of the proteins p-p38,p38,p-ERK,and ERK were assessed using Western blot analysis.Results:XYS treatment reduced the number of metastatic foci,the weights of metastatic livers,and the infiltration area of tumor-like cells.XYS could inhibit NETs formation in the liver and serum of mice with metastasis.The concentrations of CXCL1,CXCL2,G-CSF,and HMGB1 were significantly decreased in all XYS-treated groups.Moreover,XYS down-regulated the protein expression levels of phosphorylated p38 and ERK.Conclusion:XYS could attenuate liver metastases of colorectal cancer in vivo.The inhibitory mechanism of XYS may involve the reduction of NETs formation through the regulation of tumor-derived factors and the downstream MAPKs(p38,ERK)signaling pathway.
基金supported by the National Natural Science Foundation of China(82222038 and 81970259)the Chongqing Science Fund for Distinguished Young Scholars(CSTB2022NSCQ-JQX0017)+1 种基金the Outstanding Young Talents of National Defense Biotechnology(2023-JCJQ-ZQ-001 and 01-SWKJYCJJ06)the Military Key Specialized Construction Projects.
文摘Neutrophils are the first immune responders to infection.Th ey rapidly migrate to the site of infection and phagocytose pathogens.Additionally,they release neutrophil extracellular traps(NETs)to immobilize and kill pathogens via a unique form of cell death known as netosis[1,2].Recently,a groundbreaking study published in Nature reported that a subgroup of neutrophils contributes to the composition and structure of the extracellular matrix(ECM),reinforces its mechanical properties,and promotes its barrier function in both naive and wounded skin[3].The structural and functional contributions of these neutrophils support those of“professional”ECM producers(e.g.,fibroblasts)in a non-redundant manner by locally modulating the dynamics of the ECM in the skin.
基金Hunan Province College Students Research Learning and Innovative Experiment Project(S202410542120)。
文摘Despite suggested shared pathophysiological mechanisms between coronavirus disease 2019(COVID-19)and multiple sclerosis(MS),the molecular pathways underlying their relationship remain unclear.Herein,gene expression profiles of COVID-19(GSE171110,GSE152641)and MS(GSE66573,GSE159225)datasets were analyzed using Gene Ontology(GO)enrichment analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and protein-protein interaction(PPI)network construction.A two-acsample Mendelian randomization(MR)study was performed to establish potential causal relationships.A total of 165 shared differentially expressed genes(DEGs)were identified,with significant enrichment in pathways related to humoral immune response,neutrophil migration,and cytokine-receptor interactions in both conditions.Validation by receiver operating characteristic(ROC)curve analysis demonstrated that the hub genes S100A8,S100A9,S100A12,and ALOX5AP achieved area under the curve(AUC)values above 0.7 for both diseases.Increased neutrophil infiltration was positively correlated with upregulated expression of these genes,particularly demonstrating significant associations between the hub gene expression and neutrophil activity pathways.MR analysis suggested a causal relationship between S100A8 expression and susceptibility to both conditions and neutrophil counts,while ALOX5AP was indicated as a potential MS risk factor.These findings suggest that COVID-19 and MS co-occurrence is associated with neutrophil infiltration,highlighting S100A8 as both a promising biomarker and therapeutic target.
