Neutrophil Gelatinase-associated Lipocalin Research Articles

Evaluation Between Serum Concentrations of Lipocalin-2 and Metabolic Syndrome and its Components in Korean-Chinese and Han-Chinese Individuals from Yanbian Area.

Objectives: To investigate the association between the blood concentration of lipocalin-2 (LCN2) in local multiethnic residents and the increased risk for the development of metabolic syndrome (MS) in the Yanbian Korean Autonomous Prefecture population. Methods: A total of 2078 subjects with (study group) or without (control group) MS (1217 Korean-Chinese and 861 Han-Chinese subjects) were included in this study. MS subjects were divided into five groups according to ethnicity and MS components. They were assessed for smoking history, drinking history, past medical history, general demographic characteristics, and LCN2 concentrations. Results: LCN2 concentrations were higher in all ethnic MS groups than in the control group, and the highest concentrations were detected in Han-Chinese subjects with dyslipidemia. Moreover, LCN2 concentrations were significantly higher in Korean-Chinese individuals with all MS components than in the control group. Logistic regression analyses were conducted. In the unadjusted models, Korean-Chinese and Han-Chinese individuals with high LCN2 concentrations both faced a risk of MS with odds ratios (ORs) of 2.339 (95% confidence interval [CI]: 1.632-3.352) and 1.523 (95% CI: 1.101-2. 108), respectively. After the adjustment, the risk only remained in Korean-Chinese individuals, with an OR of 1.818 (95% CI: 1.031-3.207). Conclusion: Elevated circulating LCN2 was associated with the increased incidence of MS, and the effect in Korean-Chinese individuals was stronger than that in Han-Chinese individuals.

Lipocalin-2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension.

Aerobic glycolysis is involved in the pathogenesis of pulmonary hypertension (PH). The mechanisms by which glycolysis is increased and how it contributes to pulmonary vascular remodelling are not yet fully understood. In this study, we demonstrated that elevated lipocalin-2 (LCN2) in PH significantly enhances aerobic glycolysis in human pulmonary artery smooth muscle cells (PASMCs) by up-regulating LDHA expression. Knockout of Lcn2 or having heterozygous LDHA deficiency in mice significantly inhibits the progression of hypoxic PH. Our study reveals that LCN2 stimulates LDHA expression by activating Akt-HIF-1α signalling pathway. Inhibition of Akt or HIF-1α reduces LDHA expression and proliferation of PASMCs. Both Akt and HIF-1α play critical roles in the development of PH and are suppressed in the pulmonary vessels of hypoxic PH mice lacking LCN2. These findings shed light on the LCN2-Akt-HIF1α-LDHA axis in aerobic glycolysis in PH.

Assessment of cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin to distinguish acute kidney injury from other diseases in dogs.

Cell cycle arrest biomarkers (tissue inhibitor of metalloproteinase-2 [uTIMP-2] and insulin-like growth factor binding protein 7 [uIGFBP7]), and neutrophil gelatinase-associated lipocalin (NGAL) variables are valuable biomarkers for early diagnosis of acute kidney injury (AKI) in people. To evaluate uTIMP-2, uIGFBP7, fractional excretion of NGAL (FeNGAL), and urinary to serum NGAL ratio (u/sNGAL) in healthy dogs, dogs with AKI, dogs with chronic kidney disease (CKD), and critically ill (CI) dogs. Forty-two client-owned dogs (healthy, n = 10; AKI, n = 11; CKD, n = 11; CI, n = 10). Prospective, observational study. After assessment of routine renal biomarkers, stress (uTIMP-2, uIGFBP7) and damage (NGAL) biomarkers were measured, using ELISA kits, and normalized to urinary creatinine (uCr). Normalized uTIMP-2 and [uTIMP-2] × [uIGFBP7]/uCr were significantly higher in the AKI group (median 151.9 [range, 2.2-534.2] and 62.9 [1.1-266.8] pg/mL respectively), compared to healthy dogs (0.3 [0.2-74.7]; P < .001 and 0.16 [0.1-58.1] pg/mL; P < .001), dogs with CKD (0.7 [0.3-742.5]; P = .04 and 0.37 [0.2-180.1] pg/mL; P = .03) and CI dogs (1.9 [0.2-37.0]; P = .03 and 0.8 [0.1-16.1] pg/mL; P = .02). Fractional excretion of NGAL was significantly higher in dogs with AKI (54.17 [7.93-155.32] %), than in healthy (0.03 [0.01-0.21] %; P < .001) and CI dogs (3.05 [0.05-28.86] %; P = .02). Normalized uTIMP-2, [uTIMP-2] × [uIGFBP7]/uCr, and FeNGAL can be valuable renal biomarkers for early diagnosis of AKI in dogs.

Withaferin A protects against epilepsy by promoting LCN2-mediated astrocyte polarization to stopping neuronal ferroptosis

BackgroundEpilepsy is among the most frequent severe brain diseases, with few treatment options available. Neuronal ferroptosis is an important pathogenic mechanism in epilepsy. As a result, addressing ferroptosis appears to be a promising treatment approach for epilepsy. Withaferin A (WFA) is a C28 steroidal lactone that has a broad range of neuroprotective properties. Nonetheless, the antiepileptic action of WFA and the intrinsic mechanism by which it inhibits ferroptosis following epilepsy remain unknown. PurposeThis study aimed at investigating to the antiepileptic potential of WFA in epilepsy, as well as to propose a potential therapeutic approach for epilepsy therapy. MethodsWe conducted extensive research to examine the impacts of WFA on epilepsy and ferroptosis, using the kainic acid (KA)-treated primary astrocyte as an in vitro model and KA-induced temporal lobe epilepsy mice as an in vivo model. To analyze the neuroprotective effects of WFA on epileptic mice, electroencephalogram (EEG) recording, Nissl staining, and neurological function assessments such as the Morris water maze (MWM) test, Y-maze test, Elevated-plus maze (O-maze) test, and Open field test were used. Furthermore, the mechanism behind the neuroprotective effect of WFA in epilepsy was investigated using the transcriptomics analysis and verified on epileptic patient and epileptic mouse samples using Western blotting (WB) and immunofluorescence (IF) staining. In addition, WB, IF staining and specific antagonists/agonists were used to investigate astrocyte polarization and the regulatory signaling pathways involved. More critically, ferroptosis was assessed utilizing lipocalin-2 (LCN2) overexpression cell lines, siRNA knockdown, JC-1 staining, WB, IF staining, flow cytometry, electron microscopy (TEM), and ferroptosis-related GSH and MDA indicators. ResultsIn this study, we observed that WFA treatment reduced the number of recurrent seizures and time in seizure, and the loss of neurons in the hippocampal area in in epileptic mice, and even improved cognitive and anxiety impairment after epilepsy in a dose depend. Furthermore, WFA treatment was proven to enhance to the transformation of post-epileptic astrocytes from neurotoxic-type A1 to A2 astrocytes in both in vivo and in vitro experiments by inhibiting the phosphoinositide 3-kinase /AKT signaling pathway. At last, transcriptomics analysis in combination with functional experimental validation, it was discovered that WFA promoted astrocyte polarity transformation and then LCN2 in astrocytes, which inhibited neuronal ferroptosis to exert neuroprotective effects after epilepsy. In addition, we discovered significant astrocytic LCN2 expression in human TLE patient hippocampal samples. ConclusionsTaken together, for the first, our findings suggest that WFA has neuroprotective benefits in epilepsy by modulating astrocyte polarization, and that LCN2 may be a novel potential target for the prevention and treatment of ferroptosis after epilepsy.

Sodium selenite attenuates inflammatory response and oxidative stress injury by regulating the Nrf2/ARE pathway in contrast-induced acute kidney injury in rats

BackgroundContrast-induced acute kidney injury (CI-AKI) is an acute renal complication that occurs after intravascular contrast agent administration. Sodium selenite (SS) is an inorganic source of Se and has potent antioxidant properties. This study intends to examine its anti-inflammatory and antioxidant effects in CI-AKI.MethodsA rat CI-AKI model was established with the pretreatment of SS (0.35 mg/kg). Hematoxylin-eosin staining was employed for histopathological analysis of rat kidney specimens. Biochemical analysis was conducted for renal function detection. Tissue levels of oxidative stress-related markers were estimated. Reverse transcription-quantitative polymerase chain reaction revealed the mRNA levels of proinflammatory cytokines. Western blotting showed the Nrf2 signaling-related protein expression in the rat kidney.ResultsSS administration alleviated the renal pathological changes and reduced the serum levels of serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, cystatin C, and urinary level of kidney injury molecule-1 in CI-AKI rats. SS attenuated oxidative stress and inflammatory response in CI-AKI rat kidney tissues. SS activated the Nrf2 signaling transduction in the renal tissues of rats with CI-AKI.ConclusionSS ameliorates CI-AKI in rats by reducing oxidative stress and inflammation via the Nrf2 signaling.

Qualified kidney injury biomarkers demonstrate value during early clinical drug development.

Drug-induced kidney injury (DIKI) is of significant concern, both during drug development and in clinical practice. We report a patient-centric approach for clinical implementation of the FDA-qualified kidney safety biomarker panel, highlighting Phase 1 and 2 trials for candidate therapeutics in Pfizer's portfolio (PFE-1 and PFE-2, respectively) that induced kidney tubular injury in rat toxicity studies. Clusterin (CLU), cystatin-C (CysC), kidney injury molecule-1 (KIM-1), N-acetyl-beta-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin (OPN) were measured in urine samples from (i) Phase 1 healthy volunteers (HVs; n = 12) dosed with PFE-1, (ii) Phase 2 rheumatoid arthritis (RA) patients (n = 266) dosed with PFE-2, (iii) lupus patients on standard-of-care therapies (n = 121), and (iv) healthy volunteers (n = 60). The FDA-defined composite measure (CM), calculated as the geometric mean response across the 6 biomarkers, was increased ∼30% in HVs administered 100 mg PFE-1 relative to placebo, providing evidence of DIKI. In contrast, the CM for RA patients dosed with PFE-2 was comparable to placebo controls, helping to de-risk the concern for DIKI at clinically relevant doses. Comparing individual biomarker concentrations across disease states revealed that CLU, KIM-1, NAG, NGAL, and OPN are elevated in the urine of RA and lupus patients (those without severe active proliferative lupus nephritis) relative to HVs. Overall, these case studies demonstrate the value of using the FDA-qualified kidney biomarker panel to guide risk assessment, dose selection, and clinical decision making for novel therapeutics, both in HVs and patient populations.

Effects of normal saline versus isotonic balanced crystalloid on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries

BackgroundNormal saline (NS) infusion in large volumes may result in hyperchloremic metabolic acidosis and renal compromise. Balanced crystalloid (BC) with physiochemical composition akin to that of plasma may avoid these problems associated with NS. The present study aimed to evaluate effects of NS versus BC on acid–base balance and renal functions in patients undergoing intracranial tumor resection surgeries.MethodsFifty adult patients scheduled to undergo elective neurosurgery for intracranial tumor resection were randomized to receive either NS or BC as intraoperative or maintenance fluid. Metabolic and renal parameters were estimated prior to induction (baseline), at 1 h and 2 h after induction, at the end of surgery and 4 h after extubation. Serum neutrophil gelatinase-associated lipocalin (NGAL) was measured postoperatively. Brain relaxation score was assessed by the operating surgeon.ResultsBaseline values of variables were similar between the groups. At rest of the observed time-points, pH was significantly lower, while blood urea, serum creatinine, sodium, chloride, NGAL and plasma osmolality were significantly higher in the NS group as compared to the BC group. Brain relaxation score, serum bicarbonate and base excess were comparable between the two groups.ConclusionUse of balanced crystalloid (plasmalyte) resulted in better metabolic and renal profile as compared to normal saline in neurosurgical patients.

Plasma matrix metalloproteinases and tissue inhibitors of metalloproteinases explored in relation to the severity and progression of diabetic retinopathy in patients with type 1 diabetes: baseline and prospective analyses

AimsTo explore whether circulating matrix metalloproteinase-2 (MMP-2), MMP-9, MMP-9/neutrophil gelatinase-associated lipocalin, MMP-9/tissue inhibitor of metalloproteinase-1 (TIMP-1), MMP-14, TIMP-2 and TIMP-3 were associated with the severity and progression of diabetic retinopathy...

Urinary neutrophil gelatinase-associated lipocalin as early biomarker for renal disease in dogs with leishmaniosis

Canine leishmaniosis (CanL), caused by Leishmania sp., presents a wide array of symptoms; renal dysfunction is frequently observed in these dogs and is associated with a poor prognosis and increased mortality. The traditional biomarkers namely urea and creatinine can detect renal damage but only in advanced stages of the disease. However, it has been shown that the symmetric dimethylarginine assay (SDMA) or the protein/creatinine ratio (UPC) and are early biomarkers of renal dysfunction. Their elevation occurs earlier than that of creatinine, but other novel biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) are currently under investigation. Our objective was to determine whether the urine NGAL-creatinine ratio (uNGAL/c) can provide very early diagnosis of kidney disease in CanL. In total, 68 dogs were included in the study: 15 healthy dogs and 53 dogs with CanL who were classified according to International Renal Interest Society (IRIS) classification: IRIS 1 (N= 34), IRIS 2 (N= 9) and IRIS 3/4 (N= 10). IRIS 1 was subdivided according to proteinuria in IRIS 1NP (13 dogs with UPC < 0.2), IRIS 1BL (8 dogs with UPC = 0.2–0.5) and IRIS 1 P (13 dogs with UPC > 0.5). Blood samples were collected for complete hematological and biochemistry analysis including plasma NGAL. Urinalysis included specific gravity, UPC, CysC and NGAL expressed as a ratio with creatinine. The mean concentrations of pCysC and SDMA in CanL, show a statistically significant increase from IRIS 1NP, not being statistically significant for pCysC in the IRIS 1BL group. The UPC show a statistically significant increase from IRIS 1NP. In all groups with CanL for uCysC/c and uNGAL/c was observed a statistically significant increase. The uNGAL/c in the group proteinuric animals, presents a positive correlation with all renal biomarkers studied. In the group of non-proteinuric animals, the uNGAL/c presents a positive correlation with SDMA and UPC. The uNGAL/c can be considered a reliable indicator of renal disease in dogs diagnosed with CanL who are non-azotemic and non-proteinuric.

Using SWATH-MS to identify new molecular biomarkers in gingival crevicular fluid for detecting periodontitis and its response to treatment.

To identify new biomarkers to detect untreated and treated periodontitis in gingival crevicular fluid (GCF) using sequential window acquisition of all theoretical mass spectra (SWATH-MS). GCF samples were collected from 44 periodontally healthy subjects and 40 with periodontitis (Stages III-IV). In the latter, 25 improved clinically 2 months after treatment. Samples were analysed using SWATH-MS, and proteins were identified by the UniProt human-specific database. The diagnostic capability of the proteins was determined with generalized additive models to distinguish the three clinical conditions. In the untreated periodontitis vs. periodontal health modelling, five proteins showed excellent or good bias-corrected (bc)-sensitivity/bc-specificity values of >80%. These were GAPDH, ZG16B, carbonic anhydrase 1, plasma protease inhibitor C1 and haemoglobin subunit beta. GAPDH with MMP-9, MMP-8, zinc-α-2-glycoprotein and neutrophil gelatinase-associated lipocalin and ZG16B with cornulin provided increased bc-sensitivity/bc-specificity of >95%. For distinguishing treated periodontitis vs. periodontal health, most of these proteins and their combinations revealed a predictive ability similar to previous modelling. No model obtained relevant results to differentiate between periodontitis conditions. New single and dual GCF protein biomarkers showed outstanding results in discriminating untreated and treated periodontitis from periodontal health. Periodontitis conditions were indistinguishable. Future research must validate these findings.

Upconverting Nanoparticle-based Enhanced Luminescence Lateral-Flow Assay for Urinary Biomarker Monitoring.

Development of efficient portable sensors for accurately detecting biomarkers is crucial for early disease diagnosis, yet remains a significant challenge. To address this need, we introduce the enhanced luminescence lateral-flow assay, which leverages highly luminescent upconverting nanoparticles (UCNPs) alongside a portable reader and a smartphone app. The sensor's efficiency and versatility were shown for kidney health monitoring as a proof of concept. We engineered Er3+- and Tm3+-doped UCNPs coated with multiple layers, including an undoped inert matrix shell, a mesoporous silica shell, and an outer layer of gold (UCNP@mSiO2@Au). These coatings synergistically enhance emission by over 40-fold and facilitate biomolecule conjugation, rendering UCNP@mSiO2@Au easy to use and suitable for a broad range of bioapplications. Employing these optimized nanoparticles in lateral-flow assays, we successfully detected two acute kidney injury-related biomarkers─kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)─in urine samples. Using our sensor platform, KIM-1 and NGAL can be accurately detected and quantified within the range of 0.1 to 20 ng/mL, boasting impressively low limits of detection at 0.28 and 0.23 ng/mL, respectively. Validating our approach, we analyzed clinical urine samples, achieving biomarker concentrations that closely correlated with results obtained via ELISA. Importantly, our system enables biomarker quantification in less than 15 min, underscoring the performance of our novel UCNP-based approach and its potential as reliable, rapid, and user-friendly diagnostics.

Urine-derived renal epithelial cells isolated after kidney transplant are sensitive to neutrophil gelatinase-associated lipocalin exposure during in vitro culture

Urine-derived renal epithelial cells (URECs) are highly voided after kidney transplant and express typical kidney markers, including markers of kidney epithelial progenitor cells. Recently URECs have shown promising immunomodulatory properties when cultured with Peripheral Blood Mononuclear Cells (PBMCs), promoting an increase in the T regulatory cells. In vivo, kidney cells are highly exposed to damage associated molecules during both acute and chronic kidney injury. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most -known early marker of acute and chronic kidney damage. However, its role on the evolution of renal damage has not yet been fully described, nor has its impact on the characteristics of renal-derived cells during in vitro culture. The aim of this study is to investigate the effect of NGAL on the characteristics of URECs isolated after kidney transplant, by exposing these cells to the treatment with NGAL during in vitro culture and evaluating its effect on UREC viability, proliferation, and immunomodulatory potential. The exposure of URECs to NGAL reduced their viability and proliferative capacity, promoting the onset of apoptosis. The immunomodulatory properties of URECs were partially inhibited by NGAL, without affecting the increase of Treg cells observed during UREC-PBMCs coculture. These results suggest that the exposure to NGAL may compromise some features of kidney stem and specialized cell types, reducing their viability, increasing apoptosis, and partially altering their immunomodulatory properties. Thus, NGAL could represent a target for approaches acting on its inhibition or reduction to improve functional recovery.

Sakuranetin counteracts polyethylene microplastics induced nephrotoxic effects via modulation of Nrf2/Keap1 pathway

Polyethylene microplastics (PEMPs) are widely distributed in environment and exerts deleterious effects on animal as well as human health. Sakuranetin (SKN) is a natural flavonoid that manifests profound therapeutic potential. Albino rats (n = 24) were partitioned into 4 groups i.e., Control, PEMPs 1.5 mg/kg, PEMPs 1.5 mg/kg + SKN 10 mg/kg and SKN 10 mg/kg administered group. After 30 days of treatment, our results revealed that PEMPs exposure reduced nuclear factor erythroid 2–related factor 2 (Nrf-2) and antioxidant genes while enhancing the expression of kelch-like ECH-associated protein 1(Keap-1). Besides, PEMPs intoxication reduced the level of renal biomarkers i.e., creatinine clearance and increased the level of creatinine, urea, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Additionally, it lessened the activities of glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT), glutathione peroxidase (GPx) and heme oxygenase-1 (HO-1) whereas the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were increased. Conversely, it increased the levels of nuclear factor-kappa B (NF-kB), tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b) and IL-6 as well as escalated the activity of cyclooxygenase-2 (COX-2). Furthermore, the expression of bcl-2-associated X protein (Bax) and caspase-3 were elevated, while the expression of B-cell lymphoma 2 (Bcl-2) was lowered. However, SKN treatment significantly (P < 0.05) restored aforementioned renal impairments. Therefore, it is proposed that SKN may be applied as a nephroprotective agent against the PEMPs-prompted renal toxicity.

Association of protein intake with neutrophil gelatinase-associated lipocalin (NGAL) in adult critically ill patients

Nutritional support is very important for critically ill individuals considering that in this condition there are quite large metabolic changes. The American Society of Parenteral and Enteral Nutrition recommends an adequate protein diet in the early stages of severe illness. Critically ill patients experience inflammation and organ failure, resulting in elevated levels of neutrophil gelatinase-associated lipocalin (NGAL). NGAL has gained significant attention for its potential utility as an early predictor of specific organ injury and response to inflammation. Therefore, this narrative review aims to comprehensively explore the existing literature regarding the association of protein intake with NGAL levels in adult critically ill patients. The literature study method with online-based scientific databases on research engines, including Google Scholar, PubMed, Nature, and ScienceDirect, is used in this study. From this investigation, it was found that adequate protein consumption was linked to considerably lower hospital mortality rates, duration of hospitalization, and may lower NGAL levels in patients in critical condition. Based on the review of data in previous studies, it was shown that a lower protein intake at the beginning and at the mid-end of treatment may be beneficial, providing actionable insights for the care of critically ill patients.

Role of Lipocalin-2 Levels in Non-Alcoholic Fatty Pancreatic Disease and its Association with Non-Alcoholic Fatty Liver Disease

Abstract Background Lipocalin-2 (LCN2) is a 25-kDa secretory protein with great importance as a sensitive and specific screening and diagnostic biomarker for hepatic inflammation, acute hepatic injury, hepatic cancer, and radiation-induced early phase hepatic damage and lipid abnormalities. However, little is known about LCN2's functions in the homeostasis and metabolism of hepatic lipids or in the development of steatosis as well as its actual role in the event of inflammation. Aim and Objectives To establish a correlation between the levels of lipocalin as a useful biomarker with increasing severity of steatosis in NAFLD and NAFPD patients. Subjects and Methods This was observational prospective case–control study, was conducted at Hepatology Unit of Ain Shams University Hospital on 50 patients diagnosed with NAFPD and 50 healthy age and sex-matched volunteers without NAFPD during a period of 6 months. All patients were subjected to; Full history taking and thorough clinical examination, Anthropometric measurements, Laboratory investigations, and abdominal ultrasonography. Result There was a significant Positive correlation between Lipocalin 2, BMI, LDL (mg/dL), Cholesterol (mg/dL), Insulin (μU/mL) and HOMA-IR in patient group(P-value ≤ 0.001), Conclusion; lipocalin-2 is a good blood biomarker for detection of hepatic and Pancreatic steatosis. The lipocalin levels increase with increasing severity of steatosis. In addition to this, lipocalin will be useful for early diagnosis of NAFLD, NAFPD and convenient to do with other blood tests. The early intervention may prevent high morbidity and mortality and to manage the disease properly.

Value of Urinary NGAL for Predicting Acute Kidney Injury Secondary to Decompensated Cirrhosis

Abstract Background Physicians caring for patients with cirrhosis should recognize the acute or chronic character of renal disease; the causes of renal injury; the clinical conditions leading concomitantly to acute kidney injury (AKI) and liver dysfunction, and the prognostic factors associated with the progression of AKI. Hypovolemia (due to diuretics, hemorrhage, diarrhea), acute tubular necrosis, sepsis, nephrotoxic agents (such as non steroidal anti-inflammatory drugs, aminoglycosides radiological contrasts) and hepatorenal syndrome-type 1 are the most common causes of AKI in cirrhotic patients. Aim of the Work The aim of this study was to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis. Patients and Methods This was a cross sectional study done in patients with liver cirrhosis hospitalized at the Gastroenterology Department of the Ain shams university hospital. Results We found that in the comparison between HRS and AKI regarding HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, there was highly statistically significant difference found between two groups regarding Urinary Na and Fe Na%, Platelets, AST, Bilirubin and Na, and there was no statistically significant difference found between two groups regarding HB, WBCs, ALT, Albumin, INR, Urea, Creatinine and Urinary Cr. While in the Correlation between NGAL With Age, HB, WBCs, Platelets, ALT, AST, Albumin, INR, Bilirubin, Urea, Creatinine, Na, Urinary Cr, Urinary Na and FeNa%, we found that there was Non statically significant correlation Between NGAL, Age, HB, WBCs, Platelets, ALT, Albumin, INR, Bilirubin, Urea, Creatinine, Na and Urinary Cr, and there was statically significant Negative correlation Between NGAL, Urinary Na and FeNa%, and there was statically significant positive correlation Between NGAL and AST. Conclusion It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. NGAL is a newly identified member of the lipocalin family that is signifcantly expressed in injured epithelial cells. It can lead to rapid increases in NGAL secretion from glomeruli, thus increasing NGAL concentrations in the urine. In addition, its concentration often increases within 2 h of kidney injury. Urinary NGAL has the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI. These findings, if confirmed in larger cohorts, could lead to the development of biomarker algorithms to rapidly identify patients with HRS and ATN and accurately predict prognosis.

Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study. Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL-0) and 24 h after (NGAL-24). Similar analysis of C-reactive protein (CRP) was performed for additional comparison. Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL-0 (164 vs. 95 ng/mL; p < 0.001) and NGAL-24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL-0 and NGAL-24 were similar within the AKI and non-AKI groups. Using ROC curve analysis, NGAL-0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80-0.96), compared with NGAL-24 (0.783, 95% CI 0.74-0.85), CRP-0 (0.701, 95% CI 0.58-0.83), and CRP-24 (0.781, 95% CI 0.66-0.90). The optimal NGAL-0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value. Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI.

The Protecting Role of Black Seed Oil and Its Nano-Formulation in LPS-Induced Acute Kidney Injury in Mice: Evaluation of Oxidative Stress, Biochemical & Molecular Parameters.

Acute kidney injury (AKI) is a medical concern that is accompanied by the rapid deterioration of kidney function. It can be triggered by lipopolysaccharide (LPS) of gram-negative bacteria as it activates a complicated immune response, resulting in widespread inflammation and potential organ dysfunction. Black seed oil (BSO) is rich in beneficial constituents and has been widely used owing to its nutritional advantages. This research is aimed to investigate the potential protective effects of BSO and its nano-formulation on AKI induced by LPS. It also aimed to compare their anti-inflammatory activity with indomethacin, a known synthetic anti-inflammatory drug. Forty-eight mice were placed randomly into 8 groups. A single intraperitoneal (i.p.) injection of 2.5 mg/kg B.W. of LPS was used to trigger inflammation, and pretreatment with BSO and its nano-formulation was at 0.2 mL/kg/day for 14 consecutive days. Indomethacin was used as a reference drug and its efficacy was tested alone or in combination with BSO at lower doses. Renal function was assessed using urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). Also, oxidative and inflammatory markers were assessed by measuring levels of reduced glutathione (GSH), nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), and toll-like receptor-4 (TLR-4). Histopathological examination of the kidney tissues was also performed. The study showed that BSO and its nano-formulation had anti-inflammatory effects comparable to or better than those of indomethacin. They greatly decreased the oxidative stress and inflammatory markers induced by LPS. Their protective effect against pathological alterations in kidney tissues was significantly noticed. BSO and its nano-formulation could be used as nephroprotective and anti-inflammatory supplements.

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice.

Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hippocampal neuronal cultures showed that lipocalin-2 (LCN2), derived from reactive astrocytes, mediated neuroinflammation and induced cognitive impairment by decreasing the LTP through the reduction of neuronal NMDA receptors. Sustained chemogenetic stimulation of hippocampal astrocytes provided similar results. Conversely, these phenomena were attenuated by a metabolic inhibitor of astrocytes. Fiber photometry using GCaMP revealed a high level of hippocampal astrocyte activation in the neuroinflammation model. Our findings suggest that reactive astrocytes in the hippocampus are sufficient and required to induce cognitive decline through LCN2 release and synaptic modulation. This abnormal glial-neuron interaction may contribute to the pathogenesis of cognitive disturbances in neuroinflammation-associated brain conditions.

Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C: potential biomarkers for early prediction of acute kidney injury in pediatric male patients

Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C: potential biomarkers for early prediction of acute kidney injury in pediatric male patients