Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide ...Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.展开更多
Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellu...Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.展开更多
The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction b...The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.展开更多
Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research h...Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.展开更多
Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been...Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been established.Methods:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients.The effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor model.Gene knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated neutrophils.Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with PARP-1.Co-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression.Results:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(P<0.001).Neutrophil activation promoted lung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in vivo.Mechanistically,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth.Conclusion:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer progression.展开更多
Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor reg...Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.展开更多
Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regula...Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.展开更多
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio...Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.展开更多
Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders t...Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.展开更多
BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining t...BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.展开更多
Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and ...Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.展开更多
BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However...BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.展开更多
BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently ...BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently leads to neuropsychiatric co-mplications,such as cognitive impairment,anxiety,and depressive symptoms,which adversely affect patients’quality of life and rehabilitation.Neutrophil ge-latinase-associated lipocalin(NGAL)has emerged as a potential biomarker for various conditions,including AIS.This study investigated the association bet-ween serum NGAL levels at admission and neuropsychiatric complications in patients with AIS.neuropsychiatric complications in patients with AIS.METHODS Between January 2022 and December 2023,150 patients with AIS were enrolled.Serum NGAL levels were measured at admission using an enzyme-linked immu-nosorbent assay.Cognitive function was assessed using the Mini-Mental State Examination,while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge.The relationship between serum NGAL levels and cognitive impairment,anxiety,and depressive symptoms was analyzed using multivariate logistic regression,adjusted for potential con-founders of age,sex,body mass index,smoking status,hypertension,diabetes mellitus,dyslipidemia,previous stroke,and stroke severity.RESULTS The mean age of the participants was 65.4±10.2 years,and 58%were males.Prevalence rates of cognitive impairment,anxiety,and depressive symptoms at discharge were 34.7%,28.0%,and 32.0%,respectively.Serum NGAL levels were significantly higher in patients with cognitive impairment(median:5.6 ng/mL vs 3.2 ng/mL,P<0.001),anxiety(median:5.1 ng/mL vs 3.5 ng/mL,P=0.002),and depressive symptoms(median:5.4 ng/mL vs 3.3 ng/mL,P<0.001),compared to those without these conditions.Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment[odds ratio(OR)=1.42,95%confidence interval(CI):1.18-1.71,P<0.001],anxiety(OR=1.28,95%CI:1.09-1.51,P=0.003),and depressive symptoms(OR=1.39,95%CI:1.16-1.67,P<0.001)after adjusting for potential confounders.CONCLUSION Elevated serum NGAL levels were independently associated with cognitive impairment,anxiety,and depressive symptoms in patients with AIS;and may function as potential biomarkers for patients at risk.展开更多
Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospec...Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.展开更多
BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be u...BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.展开更多
Neutrophils, crucial players in the effector phase of the immune response, are recognized as important mediators of both innate and adaptive immune responses. Through the production of pro- and anti-inflammatory cytok...Neutrophils, crucial players in the effector phase of the immune response, are recognized as important mediators of both innate and adaptive immune responses. Through the production of pro- and anti-inflammatory cytokines, they modulate the function of T and other lymphoid cells. Countless reports have highlighted the importance of these cells as efficient antimicrobial agents and annotated their involvement in the pathology of infectious and noninfectious diseases. The development of modern, sophisticated technologies has allowed the study of the functions of these cells in clinical settings. These advanced technologies include fluorescence-activated cell sorters, confocal microscopy, automated cell image analyzers, and live cell analysis instruments. Unfortunately, the cost of these modern instruments, maintenance, reagents, and the need for qualified technicians prohibit their use in low-income laboratories and universities in developing countries. With this in mind, we propose a series of basic tests that can be used in low-input clinical laboratories and universities to evaluate the function of neutrophils in health and disease. Our methodology allows us to assess in a practical and low-cost manner the functions of neutrophils in the phagocytic process, including opsonization, ingestion, ROI production (NBT reduction), myeloperoxidase content, phagosome-lysosome fusion, microbicidal activity, and NET production. Thus, under a disadvantageous ambiance, this may guide physicians in deciding whether a patient’s illness involves phagocytic defects without imposing a heavy financial burden.Graphical Abstract[-rId13-]展开更多
[Objectives]This study was conducted to explore the relationship between neutrophil percentage-to-albumin ratio(NPAR)and coronary heart disease complicated with diabetes.[Methods]A total of 603 patients with coronary ...[Objectives]This study was conducted to explore the relationship between neutrophil percentage-to-albumin ratio(NPAR)and coronary heart disease complicated with diabetes.[Methods]A total of 603 patients with coronary heart disease who underwent coronary angiography in Pingquan County Hospital from January,2023 to December,2023 and met the inclusion criteria were included as the research object.All the patients were divided into a coronary heart disease complicated with diabetes group(CAD+T2DM group)(n=298 cases)and a control group(CAD group)(n=305 cases),according to patients medical history,heart color ultrasound and biochemical test results.The clinical data,biochemical test results and coronary artery imaging data of patients were recorded,and the Gensini score was calculated.The neutrophil percentage(NEUT%)and albumin count were determined to calculate NPAR.[Results]The NPAR value of the coronary heart disease complicated with diabetes mellitus group was(1.6±0.42),which was significantly higher than that of the control group(1.47±0.49),and the difference was statistically significant(P<0.05).The area under the ROC curve was 0.619(95%CI:0.591-0.675,P<0.05),and the prediction of coronary heart disease complicated with diabetes using NPAR showed a Youden index of 0.31,a sensitivity of 60.4%,a specificity of 40.3%,and a best cut-off score of 1.4506.[Conclusions]The neutrophil percentage-to-albumin ratio(NPAR)is closely related to coronary heart disease complicated with diabetes mellitus,and NPAR has clinical application value in the diagnosis of coronary heart disease complicated with diabetes mellitus.展开更多
Introduction: Hypertensive disorder in pregnancy affects 4 to 6 percent of all pregnancies and carries risks for the both baby and the mother. Only a few groups of women who are at high-risk pregnancies are received p...Introduction: Hypertensive disorder in pregnancy affects 4 to 6 percent of all pregnancies and carries risks for the both baby and the mother. Only a few groups of women who are at high-risk pregnancies are received prophylaxis Aspirin, more than 15 percent of women develop pre-eclampsia with a single minor risk factor. Methods: This descriptive cross-sectional study was conducted to compare the 1<sup>st</sup> trimester NLR value of normotensive, pregnancy induced hypertensive and pre-eclamptic pregnant women. The study was conducted with a sample of 416, antenatal patients who were admitted to ward 25, at Colombo North Teaching Hospital Ragama. Data was collected as separated three groups. NLR value was calculated separately and ANOVA test was used to analyze the 3 categorical data. Post HOC test was done to assess the multiple comparison. Results: The prevalence rates of pregnancy induced hypertension and pre-eclampsia among the pregnant women were 8.6% and 5.7%. The mean NLR values of normotensive group was 2.708, pregnancy induced hypertensive group was 2.650 and pre eclamptic group was 3.789. There was a significant difference in NLR value between pre eclamptic group and other two groups with P value of Conclusion: The 1<sup>st</sup> trimester NLR value of pre eclamptic patients significantly increased compared to normotensive women.展开更多
BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney disease.Currently,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR)...BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney disease.Currently,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR),and proteinuria.Novel urinary biomarkers utilized in the early stages of DN have been described;these indicators can be used in the early identification of the disease,which is important for initiating treatment to halt or impediment the advance of diabetic nephropathy.AIM To estimate neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and periostin(POSTN)levels as novel urinary biomarkers in DN.METHODS In this hospital based cross-sectional study,a total of 160 patients of both genders aged 18 years or more;40 healthy participants and 120 patients with diabetes mellitus(DM)were included.Patients with DM were divided into normoalbuminuria(n=40),microalbuminuria(n=40),and macroalbuminuria(n=40)groups as per urine albumin creatinine ratio(uACR).Blood urea,serum creatinine,uACR were measured.Urine NGAL,KIM-1,and POSTN were measured by enzyme linked immunosorbent assay.The eGFR was calculated and compared with urinary markers.RESULTS NGAL,KIM-1,and POSTN levels increased significantly in normo,micro,and macroalbuminuria with the highest in the macroalbuminuria group.Albumin creatinine ratio(ACR)showed a positive correlation with NGAL,KIM-1,and POSTN levels.The eGFR showed a weak negative correlation with ACR,NGAL,KIM-1,and POSTN.NGAL was significantly lower in stage 1 compared to stage 2,3,and 4 kidney disease.KIM-1 was significantly decreased in stage 1 compared to stage 4 kidney disease.POSTN was significantly decreased in stage 1 compared to stage 3 and 4 kidney disease.The receiver operator curve analysis of ACR,NGAL,KIM-1,and POSTN showed good sensitivity of 80%,75.8%,63.3%,and 80%respectively with a cut-off of 12.5 mg/g,4.5μg/L,1.5 ng/mL,and 37.5 ng/mL.CONCLUSION Urinary NGAL and POSTN are independent markers of DN.展开更多
Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), a...Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.展开更多
基金supported by the National Natural Science Foundation of China,No.32371048(to YK)the Peking University People’s Hospital Research and Development Funds,No.RDX2021-01(to YK)the Natural Science Foundation of Beijing,No.7222198(to NH)。
文摘Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still unclear.Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration.However,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear.This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury.The functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent assay.Axonal debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian degeneration.Macrophage inflammatory factor expression in different polarization states was detected using a protein chip.The results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 polarization.The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention.Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in vitro.Thus,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.
基金supported by the National Natural Science Foundation of China,No.82271399(to XC)the Project of Tianjin Applied Basic and Multiple Support Research,No.21JCZDJC00910(to XC)+4 种基金the Scientific Research Program of Tianjin Education Commission(Natural Science)of China,No.2019ZD034(to QD)the Science&Technology Program of Tianjin for Cultivation of Innovative Talents,No.22JRRCRC00020(to QD)the Tianjin Medical University"Clinical Talent Training 123 Climbing Plan"(to XC)the Tianjin Health Care Elite Prominent Young Doctor Development Program(to XC)the Young and Middle-aged Backbone Innovative Talent Program(to XC)。
文摘Neutrophil extracellular traps are primarily composed of DNA and histones and are released by neutrophils to promote inflammation and thrombosis when stimulated by various inflammato ry reactions.Neutrophil extracellular trap formation occurs through lytic and non-lytic pathways that can be further classified by formation mechanisms.Histones,von Willebrand factor,fibrin,and many other factors participate in the interplay between inflammation and thrombosis.Neuroimmunothrombosis summarizes the intricate interplay between inflammation and thrombosis during neural development and the pathogenesis of neurological diseases,providing cutting-edge insights into post-neurotrauma thrombotic events.The blood-brain barrier defends the brain and spinal cord against external assaults,and neutrophil extracellular trap involvement in blood-brain barrier disruption and immunothrombosis contributes substantially to secondary injuries in neurological diseases.Further research is needed to understand how neutrophil extracellular traps promote blood-brain barrier disruption and immunothrombosis,but recent studies have demonstrated that neutrophil extracellular traps play a crucial role in immunothrombosis,and identified modulators of neuro-immunothrombosis.However,these neurological diseases occur in blood vessels,and the mechanisms are unclear by which neutrophil extracellular traps penetrate the blood-brain barrier to participate in immunothrombosis in traumatic brain injury.This review discusses the role of neutrophil extracellular traps in neuro-immunothrombosis and explores potential therapeutic interventions to modulate neutrophil extracellular traps that may reduce immunothrombosis and improve traumatic brain injury outcomes.
基金supported in part by the Japan Agency for Medical Research and Development (AMED) under grant number JP20ek0410073, JP23ek0410108, JP22ek0410100, AMEDCREST under grant number JP19gm1210008 and AMED-PRIME under grant number JP21gm6310029, the AMED Japan Initiative for World leading Vaccine Research and Development Centers (JP223fa627001)Japan Society for the Promotion of Science (JSPS): Scientific Research S (21H05046), Scientific Research B (21H03104, 22H03195, and 22H02844) and Challenging Research (20K21515 and 21K18254)+3 种基金the JST FOREST Program (JPMJFR2261, JPMJFR205Z)Y.A. was supported by a JSPS Research Fellowship for Young Scientists (23KJ1949)Japanese Society for Immunology (JSI)Kibou Scholarship for Doctoral Students in Immunology。
文摘The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.
基金supported by the National Natural Science Foundation of China(Grant Nos.82130077,81961128025,and 82121002)the Research Projects from the Science and Technology Commission of Shanghai Municipality(Grant Nos.21JC1401200,20JC1418900,and 21JC1410100)to QG,the China National Postdoctoral Program for Innovative Talents(Grant No.BX20240090)the China Postdoctoral Science Foundation(Grant No.2024M750551)to MZ.
文摘Neutrophils,which originate from the bone marrow and are characterized by a segmented nucleus and a brief lifespan,have a crucial role in the body’s defense against infections and acute inflammation.Recent research has uncovered the complex roles of neutrophils as regulators in tumorigenesis,during which neutrophils exhibit a dualistic nature that promotes or inhibits tumor progression.This adaptability is pivotal within the tumor microenvironment(TME).In this review,we provide a comprehensive characterization of neutrophil plasticity and heterogeneity,aiming to illuminate current research findings and discuss potential therapeutic avenues.By delineating the intricate interplay of neutrophils in the TME,this review further underscores the urgent need to understand the dual functions of neutrophils with particular emphasis on the anti-tumor effects to facilitate the development of effective therapeutic strategies against cancer.
基金supported by grants from the National Key R&D Program of China(Grant No.2018YFA0900900)the National Natural Science Foundation of China(Grant Nos.82273334,82203172,81871869,and 81400055)+3 种基金the Jiangsu Province Social Development Key Projects(Grant Nos.BE2020641 and BE2020640)the Xuzhou Medical University Excellent Talent Research Start-up Fund(Grant No.RC20552157)the Jiangsu Province Capability Improvement Project through Science,Technology and Education(Grant No.CXZX202234)funded by the China Postdoctoral Science Foundation(Grant No.2023M732970)。
文摘Objective:Neutrophils are one of the most predominant infiltrating leukocytes in lung cancer tissues and are associated with lung cancer progression.How neutrophils promote lung cancer progression,however,has not been established.Methods:Kaplan–Meier plotter online analysis and tissue immunohistochemistry were used to determine the relationship between neutrophils and overall survival in lung cancer patients.The effect of neutrophils on lung cancer was determined using the Transwell migration assay,a proliferation assay,and a murine tumor model.Gene knockdown was used to determine poly ADPribose polymerase(PARP)-1 function in lung cancer-educated neutrophils.Western blot analysis and gelatin zymography were used to demonstrate the correlation between PARP-1 and matrix metallopeptidase 9(MMP-9).Immunoprecipitation coupled to mass spectrometry(IP/MS)was used to identify the proteins interacting with PARP-1.Co-immunoprecipitation(Co-IP)was used to confirm that PARP-1 interacts with arachidonate 5-lipooxygenase(ALOX5).Neutrophil PARP-1 blockage by AG14361 rescued neutrophil-promoted lung cancer progression.Results:An increased number of infiltrating neutrophils was negatively associated with overall survival in lung cancer patients(P<0.001).Neutrophil activation promoted lung cancer cell invasion,migration,and proliferation in vitro,and murine lung cancer growth in vivo.Mechanistically,PARP-1 was shown to be involved in lung cancer cell-induced neutrophil activation to increase MMP-9 expression through interacting and stabilizing ALOX5 by post-translational protein modification(PARylation).Blocking PARP-1 by gene knockdown or AG14361 significantly decreased ALOX5 expression and MMP-9 production,and eliminated neutrophil-mediated lung cancer cell invasion and in vivo tumor growth.Conclusion:We identified a novel mechanism by which PARP-1 mediates lung cancer cell-induced neutrophil activation and PARylates ALOX5 to regulate MMP-9 expression,which exacerbates lung cancer progression.
基金funding from the Liaoning Province Doctoral Start-up(grant number 2023-BS-086).
文摘Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.
基金supported by the National Natural Science Foundation of China,Nos.82271257(to YZ)and 82071228(to YZ)Qing Lan Project(to YZ)+1 种基金Open Competition Grant of Xuzhou Medical University(to YZ)Postgraduate Research&Practice Innovation Program of Jiangsu Province,No.KYCX21_2705(to TS)。
文摘Microglia-mediated neuroinflammation is considered a pathological feature of Parkinson's disease.Triggering receptor expressed on myeloid cell-1(TREM-1)can amplify the inherent immune response,and crucially,regulate inflammation.In this study,we found marked elevation of serum soluble TREM-1 in patients with Parkinson's disease that positively correlated with Parkinson's disease severity and dyskinesia.In a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease,we found that microglial TREM-1 expression also increased in the substantia nigra.Further,TREM-1 knockout alleviated dyskinesia in a mouse model of Parkinson's disease and reduced dopaminergic neuronal injury.Meanwhile,TREM-1 knockout attenuated the neuroinflammatory response,dopaminergic neuronal injury,and neutrophil migration.Next,we established an in vitro 1-methyl-4-phenyl-pyridine-induced BV2 microglia model of Parkinson's disease and treated the cells with the TREM-1 inhibitory peptide LP17.We found that LP17 treatment reduced apoptosis of dopaminergic neurons and neutrophil migration.Moreover,inhibition of neutrophil TREM-1 activation diminished dopaminergic neuronal apoptosis induced by lipopolysaccharide.TREM-1 can activate the downstream CARD9/NF-κB proinflammatory pathway via interaction with SYK.These findings suggest that TREM-1 may play a key role in mediating the damage to dopaminergic neurons in Parkinson's disease by regulating the interaction between microglia and peripheral neutrophils.
基金This work was supported by the National Natural Science Foundation of China(82071779 and 81901626)the Science Fund for Creative Research Groups of Chongqing Municipal Education Commission of China,the grants from the Talent Foundation of Army Medical University(to Shuang-Shuang Dai)+1 种基金the Scientific Research Grant(ALJ22J003)the Chongqing Natural Science Foundation of China(CSTB2022NSCQ-MSX0177).
文摘Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.
基金supported by grants from the National Traditional Chinese Medicine Inheritance and Innovation Project Fund(Development and Reform Office[2022]366)National Key Discipline of Traditional Chinese Medicine(Traditional Chinese Medicine[2023]No.85)+2 种基金the Ministry of Science and Technology National Key Research and Development Program Chinese Medicine Modernization Research Key Project(2018YFC1705204)National Nature Fund Program(82074373,82274490,82205090)Anhui Provincial Laboratory of Applied Basis and Development of Internal Medicine of Modern Traditional Chinese Medicine(2016080503B041).
文摘Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.
基金The research protocol was approved by the Clinical Trial Ethics Committee of the Affiliated Hospital of Southwest Medical University(approval number:KY2021063)registered in the Chinese Clinical Trial Registry(registration number:ChiCTR2100044198).
文摘BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in HCC.METHODS Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the Department of Oncology,the Affiliated Hospital of Southwest Medical University,Sichuan,China,from 2021 to 2023.The optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile software.Patients were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was assessed.RESULTS Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and mOS.Cox regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of OS.The time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low survival.CTC-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.
文摘Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.
基金the National Natural Science Foundation of Hunan Province,No.2023JJ60039Natural Science Foundation of Hunan Province National Health Commission,No.B202303027655+3 种基金Natural Science Foundation of Changsha Science and Technology Bureau,No.Kq2208150Wu Jieping Foundation of China,No.320.6750.2022-22-59,320.6750.2022-17-41Guangdong Association of Clinical Trials(GACT)/Chinese Thoracic Oncology Group(CTONG)and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer,No.2017B030314120.
文摘BACKGROUND Non-small cell lung cancer(NSCLC)is the primary form of lung cancer,and the combination of chemotherapy with immunotherapy offers promising treatment options for patients suffering from this disease.However,the emergence of drug resistance significantly limits the effectiveness of these therapeutic strategies.Consequently,it is imperative to devise methods for accurately detecting and evaluating the efficacy of these treatments.AIM To identify the metabolic signatures associated with neutrophil extracellular traps(NETs)and chemoimmunotherapy efficacy in NSCLC patients.METHODS In total,159 NSCLC patients undergoing first-line chemoimmunotherapy were enrolled.We first investigated the characteristics influencing clinical efficacy.Circulating levels of NETs and cytokines were measured by commercial kits.Liquid chromatography tandem mass spectrometry quantified plasma metabolites,and differential metabolites were identified.Least absolute shrinkage and selection operator,support vector machine-recursive feature elimination,and random forest algorithms were employed.By using plasma metabolic profiles and machine learning algorithms,predictive metabolic signatures were established.RESULTS First,the levels of circulating interleukin-8,neutrophil-to-lymphocyte ratio,and NETs were closely related to poor efficacy of first-line chemoimmunotherapy.Patients were classed into a low NET group or a high NET group.A total of 54 differential plasma metabolites were identified.These metabolites were primarily involved in arachidonic acid and purine metabolism.Three key metabolites were identified as crucial variables,including 8,9-epoxyeicosatrienoic acid,L-malate,and bis(monoacylglycerol)phosphate(18:1/16:0).Using metabolomic sequencing data and machine learning methods,key metabolic signatures were screened to predict NET level as well as chemoimmunotherapy efficacy.CONCLUSION The identified metabolic signatures may effectively distinguish NET levels and predict clinical benefit from chemoimmunotherapy in NSCLC patients.
基金Supported by Gansu Provincial Natural Science Foundation,No.20JR10RA671and The Fund of the First Hospital of Lanzhou University,No.ldyyyn2021-103.
文摘BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently leads to neuropsychiatric co-mplications,such as cognitive impairment,anxiety,and depressive symptoms,which adversely affect patients’quality of life and rehabilitation.Neutrophil ge-latinase-associated lipocalin(NGAL)has emerged as a potential biomarker for various conditions,including AIS.This study investigated the association bet-ween serum NGAL levels at admission and neuropsychiatric complications in patients with AIS.neuropsychiatric complications in patients with AIS.METHODS Between January 2022 and December 2023,150 patients with AIS were enrolled.Serum NGAL levels were measured at admission using an enzyme-linked immu-nosorbent assay.Cognitive function was assessed using the Mini-Mental State Examination,while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge.The relationship between serum NGAL levels and cognitive impairment,anxiety,and depressive symptoms was analyzed using multivariate logistic regression,adjusted for potential con-founders of age,sex,body mass index,smoking status,hypertension,diabetes mellitus,dyslipidemia,previous stroke,and stroke severity.RESULTS The mean age of the participants was 65.4±10.2 years,and 58%were males.Prevalence rates of cognitive impairment,anxiety,and depressive symptoms at discharge were 34.7%,28.0%,and 32.0%,respectively.Serum NGAL levels were significantly higher in patients with cognitive impairment(median:5.6 ng/mL vs 3.2 ng/mL,P<0.001),anxiety(median:5.1 ng/mL vs 3.5 ng/mL,P=0.002),and depressive symptoms(median:5.4 ng/mL vs 3.3 ng/mL,P<0.001),compared to those without these conditions.Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment[odds ratio(OR)=1.42,95%confidence interval(CI):1.18-1.71,P<0.001],anxiety(OR=1.28,95%CI:1.09-1.51,P=0.003),and depressive symptoms(OR=1.39,95%CI:1.16-1.67,P<0.001)after adjusting for potential confounders.CONCLUSION Elevated serum NGAL levels were independently associated with cognitive impairment,anxiety,and depressive symptoms in patients with AIS;and may function as potential biomarkers for patients at risk.
文摘Objective:To explore correlation of neutrophil-to-lymphocyte ratio(NLR)to severity of coronary artery disease(CAD)and in-hospital clinical outcomes in patients with acute coronary syndrome(ACS).Methods:In this prospective and observational study,we recruited 500 patients with ACS.For all the eligible patients,demographic details were collected,and laboratory parameters were evaluated.The CAD severity was evaluated in terms of the number of involved vessels.The NLR was calculated based on neutrophils and lymphocytes and the correlation of various risk factors and severity and outcome of CAD was performed.Results:77.2%of Patients was male,and 52%of the patients aged between 55-70 years.Based on the type of ACS,396 out of 500 patients had ST-elevation myocardial infarction.An ascending trend in the white blood cell levels and NLR value was noted as the severity of the ACS increased and the highest white blood cell levels and NLR was noted among classⅣpatients.The mean NLR value among the non-survivors were higher compared to the survivors(9.52±5.72 vs.4.76±2.36;P<0.01).Receiver operating curve showed that the cut-off NLR value was 5.76 with a sensitivity of 75.0%and a specificity of 77.3%.Conclusions:The NLR can be used as an independent prognostic marker in ACS.An elevated NLR value serves as a reliable predictor for short-term complications,notably in-hospital mortality.
文摘BACKGROUND Acute kidney injury(AKI)in cirrhosis is common.The diagnosis of AKI in cirrhosis patients depends on clinical presentation and laboratory tests like serum creatinine.However,urine biomarkers could also be used to assess the type of AKI and the severity of the disease.We performed a systematic review with metaanalysis to evaluate the association with urine neutrophil gelatinase-associated lipocalin(NGAL)marker in identifying acute tubular necrosis(ATN)in patients with cirrhosis.AIM To assess the reliability of urine NGAL in the detection of ATN in patients with cirrhosis.METHODS We systematically searched MEDLINE and PubMed using keywords including“urine biomarkers”,“NGAL”,“kidney dysfunction”,and“cirrhosis”to identify relevant studies.Data was screened and extracted.Included studies assessed hospitalized cirrhosis patients with AKI using the urine NGAL biomarker.We synthesized the data using diagnostic odds ratio(DOR),comparative and descriptive analyses,and Cochran Mantel-Haenszel(CMH)statistics to evaluate heterogeneity.RESULTS Three thousand seven hundred and one patients with cirrhosis were analyzed from a total of 21 cohort studies.The DOR of 14 of those studies[pooled DOR:22.150,(95%CI:17.58-27.89),P<0.0001]demonstrated a significant association between urine NGAL levels and its identification of ATN.Following stratification by cirrhosis status,heterogeneity was analyzed and showed a significant non-zero correlation between NGAL and AKI(CMH statistic=702.19,P<0.0001).CONCLUSION In patients with cirrhosis,the use of urine NGAL is a reliable biomarker for detecting ATN and identifying the etiology of AKI.
文摘Neutrophils, crucial players in the effector phase of the immune response, are recognized as important mediators of both innate and adaptive immune responses. Through the production of pro- and anti-inflammatory cytokines, they modulate the function of T and other lymphoid cells. Countless reports have highlighted the importance of these cells as efficient antimicrobial agents and annotated their involvement in the pathology of infectious and noninfectious diseases. The development of modern, sophisticated technologies has allowed the study of the functions of these cells in clinical settings. These advanced technologies include fluorescence-activated cell sorters, confocal microscopy, automated cell image analyzers, and live cell analysis instruments. Unfortunately, the cost of these modern instruments, maintenance, reagents, and the need for qualified technicians prohibit their use in low-income laboratories and universities in developing countries. With this in mind, we propose a series of basic tests that can be used in low-input clinical laboratories and universities to evaluate the function of neutrophils in health and disease. Our methodology allows us to assess in a practical and low-cost manner the functions of neutrophils in the phagocytic process, including opsonization, ingestion, ROI production (NBT reduction), myeloperoxidase content, phagosome-lysosome fusion, microbicidal activity, and NET production. Thus, under a disadvantageous ambiance, this may guide physicians in deciding whether a patient’s illness involves phagocytic defects without imposing a heavy financial burden.Graphical Abstract[-rId13-]
基金Supported by Self-financing Project of Chengde Science and Technology Program in 2023(202303A079).
文摘[Objectives]This study was conducted to explore the relationship between neutrophil percentage-to-albumin ratio(NPAR)and coronary heart disease complicated with diabetes.[Methods]A total of 603 patients with coronary heart disease who underwent coronary angiography in Pingquan County Hospital from January,2023 to December,2023 and met the inclusion criteria were included as the research object.All the patients were divided into a coronary heart disease complicated with diabetes group(CAD+T2DM group)(n=298 cases)and a control group(CAD group)(n=305 cases),according to patients medical history,heart color ultrasound and biochemical test results.The clinical data,biochemical test results and coronary artery imaging data of patients were recorded,and the Gensini score was calculated.The neutrophil percentage(NEUT%)and albumin count were determined to calculate NPAR.[Results]The NPAR value of the coronary heart disease complicated with diabetes mellitus group was(1.6±0.42),which was significantly higher than that of the control group(1.47±0.49),and the difference was statistically significant(P<0.05).The area under the ROC curve was 0.619(95%CI:0.591-0.675,P<0.05),and the prediction of coronary heart disease complicated with diabetes using NPAR showed a Youden index of 0.31,a sensitivity of 60.4%,a specificity of 40.3%,and a best cut-off score of 1.4506.[Conclusions]The neutrophil percentage-to-albumin ratio(NPAR)is closely related to coronary heart disease complicated with diabetes mellitus,and NPAR has clinical application value in the diagnosis of coronary heart disease complicated with diabetes mellitus.
文摘Introduction: Hypertensive disorder in pregnancy affects 4 to 6 percent of all pregnancies and carries risks for the both baby and the mother. Only a few groups of women who are at high-risk pregnancies are received prophylaxis Aspirin, more than 15 percent of women develop pre-eclampsia with a single minor risk factor. Methods: This descriptive cross-sectional study was conducted to compare the 1<sup>st</sup> trimester NLR value of normotensive, pregnancy induced hypertensive and pre-eclamptic pregnant women. The study was conducted with a sample of 416, antenatal patients who were admitted to ward 25, at Colombo North Teaching Hospital Ragama. Data was collected as separated three groups. NLR value was calculated separately and ANOVA test was used to analyze the 3 categorical data. Post HOC test was done to assess the multiple comparison. Results: The prevalence rates of pregnancy induced hypertension and pre-eclampsia among the pregnant women were 8.6% and 5.7%. The mean NLR values of normotensive group was 2.708, pregnancy induced hypertensive group was 2.650 and pre eclamptic group was 3.789. There was a significant difference in NLR value between pre eclamptic group and other two groups with P value of Conclusion: The 1<sup>st</sup> trimester NLR value of pre eclamptic patients significantly increased compared to normotensive women.
基金Supported by All India Institute of Medical Sciences-Bibinagar,No:AIIMS/BBN/Research/IM-F/2022/20.
文摘BACKGROUND Globally,diabetic nephropathy(DN)is the primary cause of chronic kidney disease.Currently,renal function is monitored indirectly using measures of serum creatinine,estimated glomerular filtration rate(eGFR),and proteinuria.Novel urinary biomarkers utilized in the early stages of DN have been described;these indicators can be used in the early identification of the disease,which is important for initiating treatment to halt or impediment the advance of diabetic nephropathy.AIM To estimate neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),and periostin(POSTN)levels as novel urinary biomarkers in DN.METHODS In this hospital based cross-sectional study,a total of 160 patients of both genders aged 18 years or more;40 healthy participants and 120 patients with diabetes mellitus(DM)were included.Patients with DM were divided into normoalbuminuria(n=40),microalbuminuria(n=40),and macroalbuminuria(n=40)groups as per urine albumin creatinine ratio(uACR).Blood urea,serum creatinine,uACR were measured.Urine NGAL,KIM-1,and POSTN were measured by enzyme linked immunosorbent assay.The eGFR was calculated and compared with urinary markers.RESULTS NGAL,KIM-1,and POSTN levels increased significantly in normo,micro,and macroalbuminuria with the highest in the macroalbuminuria group.Albumin creatinine ratio(ACR)showed a positive correlation with NGAL,KIM-1,and POSTN levels.The eGFR showed a weak negative correlation with ACR,NGAL,KIM-1,and POSTN.NGAL was significantly lower in stage 1 compared to stage 2,3,and 4 kidney disease.KIM-1 was significantly decreased in stage 1 compared to stage 4 kidney disease.POSTN was significantly decreased in stage 1 compared to stage 3 and 4 kidney disease.The receiver operator curve analysis of ACR,NGAL,KIM-1,and POSTN showed good sensitivity of 80%,75.8%,63.3%,and 80%respectively with a cut-off of 12.5 mg/g,4.5μg/L,1.5 ng/mL,and 37.5 ng/mL.CONCLUSION Urinary NGAL and POSTN are independent markers of DN.
文摘Introduction: Autoimmune blistering skin disorders such as Bullous Pemphigoid and Pemphigus Vulgaris present diagnostic challenges. The Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), are inflammatory markers used to assess the body’s immune-inflammatory response. Objectives: The study aims to evaluate the significance of hematologic markers, specifically the Systemic Immune-Inflammation Index (SII) and Neutrophil-Lymphocyte Ratio (NLR), as diagnostic predictors of bullous pemphigoid (BP) and pemphigus vulgaris (PV). Methods: A retrospective study of 64 patients (36 with BP and 28 with PV). Patient clinical data: age, gender, complete blood count, autoimmune antibody levels (Dsg1, 3 and BP180, 230), IgE and C-reactive protein, and history of hypertension, diabetes, brain infarction, and coronary heart disease. The data was analyzed using SPSS. Results: The study involved 36 (56.3%) diagnosed with bullous pemphigoid (BP) and 28 (43.75%) with pemphigus vulgaris (PV). The average age in BP was 71 ± 8 and 52 ± 13 in PV. Laboratory findings showed high levels of Dsg1, Dsg3, neutrophil count, and lymphocyte count in PV, while high levels of eosinophils with a significant increase in C-reactive protein (CRP) in BP. Blood biomarkers, including NLR, PLR, SII, MPV, CRP, and IgE, proved an overall of 84.4% in disease prediction. Dsg1, Dsg3, BP180, and BP230 showed an overall of 88.1%. No significant relationship was noted between NLR, SII, and patients with comorbidities. Conclusion: The study highlights the diagnostic potential of SII and NLR in addition to hematologic markers in BP and PV, emphasizing their role in early diagnosis and therapeutic interventions, requiring further validation in larger patient cohorts.
