Relationship between serum neutrophil gelatinase-associated lipocalin levels and cognitive impairment, anxiety, and depressive symptoms in acute ischemic stroke

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.

Reliability of neutrophil gelatinase-associated lipocalin in detecting acute tubular necrosis in decompensated cirrhosis:Systematic review and meta-analysis

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.

Neutrophil gelatinase-associated lipocalin,kidney injury molecule-1,and periostin:Novel urinary biomarkers in diabetic nephropathy

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.

Serum Neutrophil Gelatinase-associated Lipocalin(NGAL)Is Elevated in Patients with Asthma and Airway Obstruction

Neutrophilic airway inflammation is one of the features of severe asthma.Neutrophil gelatinase-associated lipocalin(NGAL),or lipocalin-2,is a glycoprotein associated with neutrophilic inflammation and can be detected in blood.Recently,blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease.However,the clinical significance of serum NGAL levels in patients with asthma has not been elucidated.The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma.Sixty.one non-smoking people with stable asthma were enrolled in this study.All patients underwent blood ollction and pulmonary function tests.The associations between serum NGAL levels and clinical parameters were analyzed retrospectively.Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect(76.4±51.4 ng/mL vs.39.3±27.4 ng/mL,P=0.0019).Serum NGAL levels were correlated with forced expired flow at 50%of vital capacity%predicted and forced expired flow at 75%of vital capacity%predicted(r=-0.3373,P=0.0078 and r=0.2900,P=0.0234,respectively).Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect.Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect.NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Combination of neutrophil gelatinase-associated lipocalin and matrix metalloproteinase-9 are biomarkers for the detection of colon tubular adenocarcinoma

BACKGROUND Tubular adenocarcinoma of the colon,which originates from the epithelium of the glands,is a major health concern worldwide.However,it is difficult to detect at an early stage.The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma.Neutrophil gelatinase-associated lipocalin(NGAL)is a secreted protein that induces the expression of matrix metalloproteinase-9(MMP-9)and is involved in various tumors.NGAL and MMP-9 have been reported to be associated with tumorigenesis and development.They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon.AIM To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon.METHODS Samples were collected from surgically excised tissue from various patients.The content of pro-gastrin-releasing peptide(pro-GRP)in the serum was measured by an electrochemiluminescence immunoassay.The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR,Western blotting and immunohistochemical analysis.RESULTS In this study,we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy.By analyzing the expression of NGAL in tubular adenocarcinoma at different levels,we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues.The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage(I–III),indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma.When using NGAL as a biomarker for diagnosis,the accuracy was similar to that achieved with the widely used biomarker pro-GRP,suggesting that NGAL is reliable.Moreover,the expression of MMP-9 was also strongly correlated with the differentiation stage,demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon.More importantly,the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma,and these results were further confirmed by immunohistochemical analysis of tissue sections.CONCLUSION Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

Evaluation of Reticulocyte Hemoglobin Content and Serum Neutrophil Gelatinase-Associated Lipocalin as Predictive Biomarkers of Anemia in Children on Hemodialysis

Background: Diagnosis of iron deficiency anemia with currently available tests is rendered difficult in hemodialysis patients. The aim: To investigate the role of reticulocyte Hemoglobin Content (CHr) in the diagnosis of iron deficiency anemia in hemodialysis children in comparison to the used traditional markers and assess the impressiveness and the utility of Neutrophil Gelatinase Associated Lipocalin (NGAL) as a novel biomarker of iron status in those patients. Methods: This study investigated CHr in addition to NGAL serum level in the same line with traditional markers for anemia, including: CBC, serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT%). Results: It is more significant that CHr content in hemodialysis children is lower than their controls as they are (27.06 ± 2.90) pg and (32.86 ± 3.59) pg, respectively, p = 0.01. There is no significant difference regarding NGAL between the study groups. Significant negative correlation between CHr with ferritin, urea, creatinine, and positively correlated with iron and RBCS. CHr showed a sensitivity of 90% and specificity of 86.67% to detect iron-deficiency anemia with a cut-off value of 27 pg. Conclusion: CHr is superior to ferritin and TSAT % for the early diagnosis of iron deficiency anemia in hemodialysis children;our results do not support NGAL as a marker of anemia in hemodialysis patients.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure

BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

The Differences of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels between Asphyxiated and Non-Asphyxiated Neonates

Objective: To evaluate the differences of urinary NGAL levels between asphyxiated and non-as- phyxiated neonates. Methods: This was a cross-sectional observational analytic study, including 34 newborns in Dr. Hasan Sadikin Hospital, Bandung, Indonesia. Sample collection was conducted from December 2014 to March 2015. Urine NGAL levels were evaluated using enzyme-linked immunosorbent assays (ELISA) technique. To determine the differences of urinary NGAL levels between asphyxiated and non-asphyxiated group we used Mann-Whitney U test, and to determine the differences of gestational age and birth weight between these two groups we used Fisher’s exact test. Results: Twenty males (60%) and 14 females (40%) neonates participated in the study. From 34 subjects, 17 neonates were diagnosed with asphyxia and 17 neonates without asphyxia. The results showed that urine NGAL levels had significantly increased in asphyxiated neonates. The median urine NGAL level in asphyxiated group is 95% CI: 506.7 (60.0 - 651.7) ng/mL, while the median urine NGAL level in non-asphyxiated group is 95% CI: 6.7 (0.1 - 53.0) ng/mL. Statistically, there were significant urine NGAL levels differences between asphyxiated and non-asphyxi- ated neonates (p < 0.001). There were no differences in gestational age and birth weight between asphyxiated and non-asphyxiated neonates (p > 0.05). Conclusions: Urinary NGAL levels in asphyxiated neonates were significantly higher than those in non-asphyxiated neonates. There were significant differences of urine NGAL levels between the groups.

Urinary neutrophil gelatinase-associated lipocalin(NGAL)and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU

Background Acute kidney injury(AKI)is common in critically ill children with significant mortality and morbidity.Serum creatinine is an insensitive and late biomarker compared to newly proposed AKI biomarkers.Methods Prospective study in pediatric intensive care unit(PICU)over three months to compare between serum cystatin-C(s-Cys-C)and urinary neutrophil gelatinase-associated lipocalin(uNGAL)as AKI biomarkers at multiple time points with pediatric risk,injury,failure,loss,end-stage renal disease(pRIFLE)classification in diagnosing AKI.Results Forty children were recruited.Of these 40 children,22 developed AKI according to pRIFLE criteria.There was no significant difference between AKI and non-AKI in age(P=0.29).Post cardiac surgery,renal insult was the main cause of AKI(27.3%).There was a twofold increased risk of incident AKI in those patients with high baseline uNGAL at PICU admission and almost a fourfold increased risk in patients with high baseline s-Cys-C at PICU admission.uNGAL levels were highly predictive of AKI during the follow-up period[area under the curve(AUC)=0.76,95%confidence interval(CI)0.61-0.92].The cutoff point with the highest correctly classified proportion was 223 ng/mL(≥12 centiles)which correctly predict 80.0%patients with AKI,with a corresponding sensitivity of 72.7%and a specificity of 89.9%.AUC for s-Cys-C was 0.86(95%CI 0.75-0.97),and the highest correctly classified proportion was 1009μg/L(≥13 centiles);75%of patients with AKI,with a corresponding sensitivity of 63.6%and a specificity of 88.9%.Conclusion uNGAL and s-Cys-C predicts AKI early in critically ill children.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi Compatibility on Uric Acid Metabolism and Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Rats with Hyperuricemia

Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kidney injury molecule-1（KIM-1） in rats with hyperuricemia. Methods：Seventy male Sprague Dawley（SD） rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses（3.5, 7, 14 g/kg）. Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid（SUA）, blood urea nitrogen（BUN） and creatinine（Cr） were determined. In addition, the contents of NGAL and KIM-1 in urine and the m RNA and protein expressions of xanthine oxidase（XOD） in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin（HE） stain method. Results：Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD m RNA and protein in the hyperuricemia rats were increased significantly（P〈0.01）. PR significantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the m RNA and protein expressions of hepatic XOD（P〈0.05 or P〈0.01）. In addition, the pathological changes of kidney were significantly suppressed by oral administration of PR. Conclusions：PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

Urine neutrophil gelatinase-associated lipocalin at SICU admission predicts for cardiac surgery-associated acute kidney injury

Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney injury （CSA-AKI） and have an earlier response to acute kidney injury. The association between urine neutrophil gelatinase-associated lipocalin （NGAL） concentrations and AKI progression is not well established. Methods The prospective-cohort study included 1631 consecutive adult patients undergoing cardiac surgery at Fuwai Hospital between September 2012 and November 2013. AKI defined by Acute Kidney Injury Network （AKIN） criteria with a postoperative increase in plasma creatinine 〉/50% baseline or/〉0.3 mg/dL. Urine NGAL was measured us- ing latex particle-enhanced turbidimetric immunoassay. Associations between Urine NGAL levels and AKI were determined by estimating areas under receiver operating characteristic curves （AUC）. Results A total of 438 （26.9%） patients developed CSA-AKI. And the patients were divided into four groups： 1193 non-AKI patients, 368（22.6%） patients with AKIN stage I AKI, 49（3.0%） with AKIN stage 2 AKI and 21（1.3%） with AKIN stage 3 AKI. urine NGAL concentrations at surgical intensive care unit （SICU） admission were significantly related to AKI severity. The AUCs for urine NGAL were for AKIN stage 1 （0.54±0.02）, AKIN stage 2 （0.67±0.04）, and AKIN stage 3 （0.76±0.06）, respectively. Conclusions Urinary NGAL is associated with CSA-AKI and its progression, indicating their potential use as prognostic markers. Urine NGAL level measured at SICU admission predicts the development of severe AKI after cardiac surgery.

Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney affection in diabetic patients. The aim of this work is to investigate urinary NGAL (UNGAL) in type 2 diabetic patients with and without albuminuria. Methods: This study included 46 type 2 diabetic patients and 15 healthy age and sex matched individuals as the control group. Diabetic patients were divided into three groups according to urinary albumin excretion (UAE), normoalbuminuria, microalbuminuria and macroalbuminuria. UNGAL was measured in all populations and corrected to urinary creatinine to account for day to day variation in urine volume and transformed log. Comparison between 4 groups (control, normoalbuminuria, microalbuminuria and macroalbuminuria) was done. Results: Log UNGAL/Creatinine ratio showed significant difference when comparing control group (0.70 ± 0.58) versus normoalbuminuria (1.71 ± 1.06), microalbuminuria (1.57 ± 0.72) and macroalbuminuria (1.92 ± 0.63), however, there was no significant difference among diabetic groups. Pearson’s correlation showed that log UNGAL/Creatinine ratio positively correlated with glycated hemoglobin (HbA1c) and inversely with estimated glomerular filtration rate (eGFR). Regression analysis showed that HbA1c, urinary creatinine and eGFR were the independent predictors of log UNGAL/Creatinine ratio. Conclusion: Tubular markers like UNGAL may be early elevated in type 2 diabetic patients even before the incidence of glomerular injury detected by microalbuminuria and it can be used as an early marker for detection of kidney involvement in diabetic patients.

Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. Differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR < 60 mL/min vs patients with e GFR ≥ 90 mL/min. Differences in NGAL were not significant among patients ranked by HCV viral load, FIB-4 score and APRI, when patients with NGAL > 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

Levels of neutrophil gelatinase-assosciated lipocalin in patients with head and neck squamous cell carcinoma in Indian population from Haryana state

AIM To study the levels of neutrophil gelatinase associated lipocalin(NGAL) in head and neck squamous cell carcinoma(HNSCC).METHODS This was a non randomized case control study conducted at Department of Biochemistry,in collaboration with Regional Cancer Center over a period of one year.The study population included 50 adult newly diagnosed HNSCC patients reporting in outpatient department at Regional Cancer Center and compared with 50 healthy controls.NGAL was estimated by ELISA technique.Student t test and χ~2 test were applied for comparison of means of study groups.Correlations between groups were analyzed using Pearson correlation coefficient(r) formula.RESULTS Patients with HNSCC exhibited significantly increased levels of NGAL(P < 0.05) as compared to healthy controls(978.88 ± 261.39 ng/mL vs 34.83 ± 7.59 ng/mL).Out of 50,26 patients(52%) were in stage Ⅳ,21(42%) in stage Ⅲ,1(2%) patient in stage Ⅱ and 2(4%) patients were in stage Ⅰ.Metastasis was absent in 98% patients and mean NGAL levels were highest in these patients but P value was not significant.Mean NGAL levels were highest in stage Ⅳ [1041.54 ± 222.15 ng/mL(stage Ⅳ) vs 1040 ± 0.00 ng/mL(stage Ⅰ);900 ± 0.00 ng/mL(stage Ⅱ) and 1031.90 ± 202.55 ng/mL(stage Ⅲ)] and χ~2 test was highly significant(P < 0.001).Thirty-six patients(72%) were having moderately differentiated HNSCC and mean NGAL levels were maximum in patients with well differentiated HNSCC(1164 ± 315.64 ng/mL vs 1013.33 ± 161.19 ng/mL in moderately differentiated and 890 ± 11.55 ng/mL in poorly differentiated) and the results were also highly significant(P < 0.001,χ~2 test).CONCLUSION The present work demonstrates a potential role of NGAL as cancer biomarker and its use in monitoring the HNSCC progression.

Correlation between Serum Neutrophil Gelatinase Associated Lipocalin and Burn Severity: A Pilot Study

The severity of an initial burn injury is critical for determining the treatment plan and prognosis of burn patients. Here, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels to determine whether NGAL can be used as a biomarker for severity of burn injuries. A study of the demographic, clinical, and laboratory markers for various organ damage was performed at Bestian Burn Center (n = 10 healthy people, n = 31 patients). NGAL and organ damage marker levels were measured in 31 patients with severe burns within 2 - 3 days following their admission to the intensive care unit. Serum NGAL level of the expired patients was 788.5 (685.0 - 998.0) pg/mL, whereas that of the discharged patients was 421.2 (356.2 - 480.6) pg/mL, showing that the initial serum NGAL level can be used to estimate mortality. We also determined the correlation between serum NGAL level and the currently used severity markers (total body surface area burned and abbreviated burn severity index) and confirmed that serum NGAL level could be used as a severity marker. We also found that serum NGAL level was correlated with damage of organs such as the liver, kidney, heart, and respiratory organs in patients with severe burns.

Study of Lipocalin-2 Associated with Neutrophilic Gelatinases (uNGAL) in the Urine in Children with the Microbial Inflammatory Diseases of Kidneys and Urinary Tract

Purpose of the study: Research of the clinical and diagnostic significance of determination of Lipocalin-2 associated with neutrophilic gelatinases (uNGAL) in the urine of children with urinary tract infection (UTI) and pyelonephritis. Materials and methods: We examined 30 children with acute pyelonephritis and UTI aged 1 to 16 years (average age 7.32 ± 4.52) including 26 girls and 4 boys. Verification of the diagnosis was conducted on the basis of clinical and laboratory data, medical history and instrumental examination of patients. All children were divided into 2 groups: 1st group—15 children with acute pyelonephritis, 2nd group—15 children with urinary tract infection. uNGAL was measured in the urine by enzyme-linked immunosorbent assay (EISA) (BioVendor Laboratoty Medicine). Results: It is found, that the urine level of NGAL depends on the damage degree of renal parenchyma. The correlation of medium strength was found between the excretion level of uNGAL during the acute period of pyelonephritis and the detection of renal scars according to the DMSA-nephroscintigraphy data. In the group of children with the acute pyelonephritis the direct correlation of medium strength was found between the excretion level of uNGAL/creatinine and leukocytosis value and also with the CRP blood level. Conclusion: The results allow us to recommend the determination of the excretion level of uNGAL/creatinine as an additional non-invasive marker for the early detection of renal parenchyma injury.

大鼠脓毒症肺损伤与中性粒细胞载脂蛋白的相关性研究

目的探究大鼠脓毒症肺损伤与中性粒细胞载脂蛋白(HNL)的相关性。方法45只大鼠按照随机方法分为对照组、sham组及模型组,模型组建立脓毒症肺损伤大鼠模型,sham组开腹后仅游离盲肠后关腹,不进行结扎和穿刺,对照组为健康大鼠。使用试剂盒检测各组大鼠血清白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α(TNF-α)及HNL;血气分析仪检测氧合指数;计算肺组织湿/干比;HE染色观察肺组织病理形态,计算肺损伤评分。结果对照组及sham组12、24、36 h的IL-6、IL-1β、TNF-α、HNL水平、氧合指数、肺组织湿/干比、肺损伤评分比较,差异均无统计学意义(均P>0.05);与sham组相比,模型组12、24、36 h的IL-6、IL-1β、TNF-α、HNL水平、氧合指数、肺组织湿/干比、肺损伤评分均升高,差异均有统计学意义(均P<0.05)。对照组大鼠12、24、36 h肺组织结构正常,且未见水肿,sham组大鼠12、24、36 h肺组织仅有少量炎症细胞,模型组大鼠12、24、36 h肺组织结构严重破坏,肺泡萎陷,炎症细胞严重浸润,但随着时间延长病理改善。脓毒症肺损伤大鼠中,HNL与IL-6、IL-1β、TNF-α、肺部湿/干比、肺损伤评分呈现正相关性(均P<0.05),与氧合指数呈现负相关性(P<0.05)。结论脓毒症肺损伤大鼠中HNL显著升高,炎症反应严重,肺组织湿/干比、肺损伤加重,氧合指数降低,且HNL水平与IL-6、IL-1β、TNF-α水平、肺组织湿/干比、肺损伤呈正相关性,与氧合指数呈负相关性。

血清LRG1、NGAL和PGC-1α水平与小儿肾积水手术后分肾功能的相关性研究

目的探究血清富亮氨酸α2-糖蛋白1(leucine-richα2 glycoprotein 1,LRG1)、中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、过氧化物酶体增殖物激活受体γ辅助激活因子-1α(peroxisome proliferator activated receptorγcoactivator-1α,PGC-1α)水平与小儿肾积水术后分肾功能(differential renal function,DRF)的相关性。方法本研究为回顾性研究,选取邯郸市中心医院2019年3月至2022年6月期间行肾盂输尿管成形术的124例肾积水患儿作为研究对象,根据术后18个月DRF情况,将患儿分为DRF≥45%组(n=72)和DRF<45%组(n=52)。采用酶联免疫吸附法检测患儿血清中LRG1、NGAL和PGC-1α水平。采用Pearson相关性分析探讨血清LRG1、NGAL、PGC-1α水平与肾功能的相关性,采用二元Logistic回归分析肾积水患儿术后DRF<45%的影响因素,通过受试者工作特征(receiver operating characteristic,ROC)曲线分析血清LRG1、NGAL、PGC-1α对肾积水患儿术后DRF的预测价值。结果DRF≥45%组和DRF<45%组患儿血清LRG1分别为(184.28±55.46)ng/mL、(315.62±98.53)ng/mL(t=9.437,P<0.05);肌酐(rerum Creatinine,Scr)分别为(26.84±7.64)μmol/L和(35.46±10.27)μmol/L(t=5.361,P<0.05);尿素氮(blood urea nitrogen,BUN)分别为(5.24±1.52)mmol/L和(7.23±2.31)mmol/L(t=5.783,P<0.05);β_(2)-微球蛋白(β_(2)-microglobulin,β_(2)-MG)分别为(2.16±0.43)mg/L和(3.68±0.84)mg/L(t=13.164,P<0.05);PGC-1α分别为(4.26±1.14)ng/mL和(2.85±0.89)ng/mL(t=7.430,P<0.05);术前患侧DRF分别为(43.25±4.57)%和(31.58±3.68)%(t=15.192,P<0.05);差异均有统计学意义。Pearson相关性分析结果显示,LRG1、NGAL与Scr、BUN、β_(2)-MG呈正相关(P<0.05);PGC-1α与β_(2)-MG、Scr、BUN呈负相关(P<0.05)。Logistic回归分析显示,血清LRG1、NGAL、Scr、BUN、β_(2)-MG、PGC-1α、术前患侧DRF是术后DRF<45%的影响因素(P<0.05)。ROC曲线分析显示,血清LRG1、NGAL、PGC-1α及三者联合评估肾积水患儿术后DRF<45%的曲线下面积(area under the curve,AUC)分别为0.899、0.872、0.878及0.982,三者联合评估优于单独评估(Z_(三者联合-LRG1)=3.148、Z_(三者联合-NGAL)=3.937、Z_(三者联合-PGC-1α)=3.125,P<0.05)。结论肾积水术后DRF<45%的患儿血清中LRG1、NGAL水平升高,PGC-1α水平降低,三者联合检测对于术后DRF具有一定的预测价值。

PTEN、CA125、sVEGFR1、NGAL在子宫内膜癌患者血清中的表达及与病理特征的关系

目的 探讨第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)、糖类抗原125(CA125)、可溶性血管内皮生长因子受体-1(sVEGFR1)、中性粒细胞明胶酶相关脂质载运蛋白(NGAL)在子宫内膜癌(EC)患者血清中的表达及与病理特征的关系。方法 选取2019年1月至2021年6月于在邯郸市第一医院行全子宫切除术并经病理诊断的120例EC患者为研究组,选择同期80例良性病变子宫内膜患者为对照组,用酶联免疫吸附法检测并比较2组患者血清PTEN、CA125、sVEGFR1、NGAL水平,收集2组临床病理资料,分析血清PTEN、CA125、sVEGFR1、NGAL与研究组患者病理特征的关系。结果 研究组血清CA125、NGAL水平高于对照组,血清PTEN、sVEGFR1水平低于对照组(P<0.05)。分化程度越低血清CA125、NGAL水平越高,血清PTEN、sVEGFR1水平越低(P<0.05);临床分期Ⅲ~Ⅳ期患者血清PTEN高于Ⅰ~Ⅱ期(P<0.05);临床分期Ⅲ~Ⅳ期、有淋巴结转移、浸润深度≥50%患者血清CA125、NGAL水平升高,血清sVEGFR1水平降低(P<0.05)。血清PTEN与临床分期呈负相关,与分化程度呈正相关(P<0.05);血清CA125、NGAL与临床分期、淋巴结转移、浸润深度呈正相关,与分化程度呈负相关(P<0.05);血清sVEGFR1与临床分期、淋巴结转移、浸润深度呈负相关,与分化程度呈正相关(P<0.05)。结论 CA125、NGAL在EC患者血清中呈高表达,PTEN、sVEGFR1呈低表达,均与EC患者病理特征有一定相关性,可作为EC早期诊断与疾病进展的潜在生物学标志物。

急、慢性肾损伤患者血清中生物标志物的研究与验证

目的:探讨血清中中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及其他生物标志物在急、慢性肾损伤患者中的临床应用价值。方法:选取2022年1月~2023年7月在广州市中山大学附属第三医院就诊的急性肾损伤(acute kidney injury,AKI)患者171例及慢性肾脏病(chronic kidney disease,CKD)患者209例。收集各组成员的钾(K)、钠(Na)、氯(Cl)、二氧化碳(CO_(2))、尿素(Urea)和葡萄糖(GLU)数据。选取同时期健康体检者94例作为健康对照组,并用胶乳免疫比浊法检测3组成员血清中的NGAL水平。分析血清NGAL和其他生物标志物在鉴定急性和慢性肾损伤中的诊断有效性。采用多因素logistic回归方程分析影响AKI和CKD患者发生的因素。此外,还构建了受试者工作特征(receiver operating characteristic,ROC)曲线,以评估这些生物标志物在肾损伤患者中的临床意义。结果:通过生物信息学分析,提示NGAL可能是肾损伤的检测标志物。一般资料显示,在AKI组及CKD组中,K、Na、CO_(2)、Urea、GLU和NGAL水平均高于健康对照组(P<0.05)。多因素logistic回归方程分析显示,Na、Urea、GLU和NGAL水平均为AKI或者CKD疾病发生的独立危险因素(P<0.05)。ROC曲线分析结果显示,在AKI组中,Na、Urea、GLU和NGAL的曲线下面积(area under curve,AUC)分别为0.711、0.960、0.793和0.841(P<0.01);在CKD组中,Na、Urea、GLU和NGAL的AUC分别为0.681、0.990、0.703和0.930(P<0.01)。NGAL和Urea联合诊断AKI的灵敏度和特异性分别是81.9%和61.1%,诊断CKD的灵敏度和特异性分别是62.7%和80.0%。结论:血清NGAL可作为急、慢性肾损伤的指标,联合其他生物标志物在急、慢性肾损伤中也有一定的临床应用价值。