Does LCN2 Play a Critical Role in the Pathogenesis of Depression?

Integrated SERS-magnetic capture platform for multiplex detection of early tubular injury biomarkers in diabetic kidney disease progression

Rutin outperforms gallic acid in mitigating carbon tetrachloride-induced nephrotoxicity: Integrated in silico (docking, MD simulations, DFT) and in vivo mechanistic validation.

Development of a novel high-affinity anti-NGAL monoclonal antibody pair for sensitive detection of acute kidney injury.

Urinary NGAL as an early marker of subclinical kidney injury in adults with substance use disorder: A case-control study.

Sickle cell disease (SCD) is characterized by chronic hemolysis, inflammation, and progressive kidney injury which leads to renal failure and increased mortality rates with limited therapeutic options available. Neuregulin-1 (NRG-1) is a cytoprotective growth factor with anti-inflammatory and antioxidant properties and an established clinical safety profile in humans. Using Townes humanized sickle cell (HbSS) mice, we investigated whether NRG-1 mitigates kidney injury by reducing hemolytic and inflammatory mediators and enhancing renal cytoprotective and repair factors. NRG-1 treatment reduced plasma heme, lactate dehydrogenase, and pro-inflammatory cytokines levels, while increasing the proportion of circulating fetal hemoglobin-containing red blood cells (F-cells). Treatment mitigated urinary cystatin C and neutrophil gelatinase-associated lipocalin (NGAL)elevations and improved renal histopathology, including reduced iron deposition, glomerular congestion, and sclerosis. NRG-1 also enhanced heme oxygenase-1 (HO-1) expression in HbSS kidneys and increased urinary renal repair biomarkers clusterin and epidermal growth factor (EGF). Collectively, these findings provide new mechanistic insight supporting further exploration of NRG-1 as a therapeutic agent for mitigating kidney injury in SCD.

Diagnostic accuracy of NGAL and HBP for the diagnosis of acute bacterial meningitis.

Prostate cancer (PCa) is a hormone-dependent tumor and one of the most prevalent cancers in men worldwide. PCa progression is influenced by its interaction with the surrounding tumor microenvironment, highlighting the role of periprostatic adipose tissue (PPAT), which modulates PCa behavior through the secretion of bioactive molecules (e.g., adipokines). However, the influence of this complex cell communication, particularly under altered metabolic conditions, remains to be fully elucidated. We performed multiomic/bioinformatic approaches integrating transcriptomic, proteomic, and metabolomic data from PPATs and their secretome and circulating/urinary of lipocalin-2 (LCN2) levels using a well-characterized cohort [75 PCa-patients vs. 22 control subjects with benign prostate hyperplasia (BPH)]. Different prostate cell models [normal-like (PNT2) and PCa cells (DU145/LNCaP/22Rv1/PC-3)] were used to test the role of the LCN2/SLC22A17 axis in PCa cell via multiple functional (proliferation/apoptosis/migration/invasion/colony-formation/tumorsphere assays), molecular (transcriptomic/phospho-proteomic/targeted inflammatory proteomics), and preclinical (in vivo xenograft) analyses. External validation was performed using TCGA, Grasso, and Taylor cohorts, alongside longitudinal proteomic data from patient-derived xenograft models. A signature of significantly dysregulated adipokines was identified in PPAT of PCa vs. BPH patients. Unsupervised clustering analyses revealed two distinct molecular phenotypes (T1/T2) with unique adipokine fingerprints associated with differential obesity-related comorbidities (BMI/diabetes/dyslipidemia), being LCN2 the only adipokine showing consistent dysregulation at the transcriptomic/proteomic levels. Functional experiments demonstrated that LCN2 and its receptor SLC22A17 exert context- and transformation state-dependent effects [i.e., in vitro LCN2 and SLC22A17 overexpression promoting migration capacity in normal-like cells, while suppressing aggressive phenotypes (proliferation/invasion/stemness) in malignant models; these findings being also confirmed on in vivo xenograft models]. SLC22A17 expression was progressively lost during PCa progression and associated with significantly poorer survival across multiple independent cohorts. Mechanistically, LCN2 modulated critical oncogenic and inflammatory pathways, including NF-κB, TGF-β, JAK/STAT, and inflammasome-related signaling, and showed obesity-specific associations with arachidonic acid and complement components in the PPAT secretome. These results demonstrate a profound dysregulation of the PPAT-derived adipokine profile in PCa associated with obesity-related comorbidities, and reveal a paradoxical, stage- and context-dependent dual role of the LCN2/SLC22A17 axis as a key modulator of PPAT-PCa microenvironment interactions, with potential implications for inflammation, metabolic signaling, and tumor progression.

Peripheral neutrophil levels in amyotrophic lateral sclerosis (ALS) inversely correlate with survival, suggesting a role for neutrophils in disease progression. Here, we characterize markers of several neutrophil activation pathways and evaluate their associations with survival to identify potential mechanisms of disease. Blood samples were obtained from participants at the University of Michigan ALS Clinic or from healthy controls. Exvivo neutrophil extracellular trap (NET) formation was quantified via image analysis of primary neutrophils. Neutrophil function markers of general activation (calprotectin), migration (matrix-metalloproteinase 9 [MMP9]), and degranulation (neutrophil gelatinase-associated lipocalin [NGAL]) were then quantified in plasma via ELISA; NET formation (double-stranded DNA [dsDNA]) was assessed via fluorescence assay. These markers were then associated with ALS survival using Cox proportional hazard regression models, and analyses were stratified by sex. Spontaneous exvivo NET formation (N = 20 controls, 66 ALS) was increased in ALS (1.0% vs. 9.7%; p = 0.017). In plasma (N = 233 controls, 178 ALS), calprotectin (294 vs. 372 ng/mL; p < 0.001), MMP9 (106 vs. 152 ng/mL; p < 0.001), and NGAL (61 vs. 66 ng/mL; p = 0.01) were elevated in ALS. Calprotectin, MMP9, and NGAL levels were not associated with ALS survival; however, dsDNA was associated with poorer ALS survival but only in females (HR = 1.77 [95% CI, 1.20-2.61]; p = 0.004). Neutrophil function is altered in ALS, and NET formation is a potential mechanism by which neutrophils contribute to ALS, particularly in females.

Periprosthetic joint infection (PJI) remains one of the most serious complications after joint arthroplasty, and accurate diagnosis continues to pose significant challenges. A reliable distinction between septic and aseptic failure is essential for appropriate surgical and antibiotic management. This systematic review and meta-analysis evaluate the most recent clinical evidence on the diagnostic accuracy, methodological quality, and standardization potential of established "classical" and emerging serum and synovial biomarkers for PJI diagnosis. This systematic review and meta-analysis were conducted in accordance with PRISMA-DTA guidelines, with PRISMA used as a general reporting framework. Selected items from the STARD checklist were used solely to inform data extraction and were not applied as a reporting guideline. Clinical studies published between January 1, 2020, and October 31, 2025, were identified through PubMed, Scopus, and Web of Science. Eligible studies reported sensitivity, specificity, and/or diagnostic thresholds for serum or synovial biomarkers based on MSIS, ICM, or EBJIS criteria for PJI definition. Study quality was assessed using the QUADAS-C tool, and a meta-analysis of chronic PJI cohorts was performed. Twenty-six studies were included (8 serum, 18 synovial). Among serum biomarkers, C-reactive protein and erythrocyte sedimentation rate showed moderate diagnostic accuracy (Area Under the ROC curve [AUC] 0.82-0.90), while fibrinogen demonstrated comparable performance in selected cohorts. D-dimer and other coagulation indices showed variable results. Synovial biomarkers demonstrated superior diagnostic performance. α-defensin, D-lactate, calprotectin (CP), and neutrophil gelatinase-associated lipocalin achieved excellent accuracy (AUC > 0.90; sensitivity and specificity > 90%). Synovial white blood cell count (WBC) and polymorphonuclear percentage (PMN%) remained reliable and cost-effective. Meta-analysis confirmed high pooled diagnostic performance for WBC (0.88/0.97) and PMN% (0.84/0.97). Traditional serum biomarkers remain useful first-line diagnostic tools, whereas synovial biomarkers-particularly α-defensin, D-lactate, CP, and WBC indices-demonstrate superior diagnostic accuracy and may be especially valuable in culture-negative PJI. However, substantial heterogeneity and risk of bias identified by QUADAS-C-particularly in patient selection, reference standards, and threshold derivation-suggest that pooled estimates may represent optimistic upper-bound performance, limiting generalizability. Future diagnostic strategies should integrate multimodal biomarker panels with molecular diagnostics and artificial intelligence-based approaches to improve diagnostic precision and clinical applicability.

Effect of perioperative fluid therapy on urinary biomarkers in preeclamptic women who underwent caesarean section - A randomised controlled trial.

Abstract Background Bone-derived hormones, including lipocalin-2 (LCN2) and osteocalcin, are increasingly recognized for their roles in glucose metabolism and insulin sensitivity. Their patterns across normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM) remain underexplored. Objectives To evaluate serum LCN2 and osteocalcin levels in obese and non-obese T2DM cases, prediabetic individuals, and healthy controls, and to assess their associations with insulin resistance (IR) and metabolic parameters. Methods In this case–control study, 124 adults aged 30–60 years were equally allocated into four groups: obese T2DM, non-obese T2DM, prediabetes, and healthy controls ( n = 31 each). Anthropometric data, fasting and postprandial glucose, HbA1c, insulin, lipid profile, serum LCN2, and osteocalcin were measured. Results LCN2 levels were significantly lower in diabetics (8.0 ± 1.0 ng/mL) and higher in prediabetics (8.7 ± 0.5 ng/mL) compared to controls (8.7 ± 0.3 ng/mL; p &lt; 0.001). Osteocalcin was higher in diabetics (median 6.6 ng/mL) than in prediabetics (6.1 ng/mL) and controls (5.4 ng/mL), though differences were not significant ( p = 0.327). In multivariate analysis, decreased LCN2 (OR = 0.24, 95% CI 0.07–0.76), higher TGs (OR = 1.03 per mg/dL), and higher insulin (OR = 1.13 per µU/mL) independently predicted T2DM. For prediabetes, TGs were the strongest predictor (OR = 1.03 per mg/dL). LCN2 correlated negatively with fasting glucose ( r =–0.44) and 2-hour postprandial glucose ( r =–0.58) in prediabetes, and positively with osteocalcin in both groups. ROC analysis for LCN2 in predicting diabetes showed an AUC of 0.66 (cut-off ≤ 8.3 ng/mL; 44% sensitivity, 77% specificity). Conclusion LCN2 and osteocalcin demonstrate potential as early markers of metabolic disturbance. Altered LCN2 patterns suggest an inflammation-related response in prediabetes and depletion in overt diabetes.

Sacubitril/valsartan shows benefits in heart failure and may have kidney protective effects. Its impact on kidney tubular health in chronic kidney disease (CKD) remains unclear. We evaluated the effects of sacubitril/valsartan on urinary markers of tubular dysfunction and injury in UK Heart and Renal Protection-III (HARP III, ISRCTN:11958993). Urine tubular biomarkers were measured at baseline, 3 and 6 months using first morning void or spot urine samples among 411 participants from UK HARP III. A mixed model repeated measures approach was used to quantify the study average effect of treatment on the urine biomarkers. Compared to allocation to irbesartan, allocation to sacubitril/valsartan reduced neutrophil-gelatinase associated lipocalin (NGAL), a marker secreted in the distal tubules after ischemia and reperfusion, by 18% (95% CI: -32% to -1%). No significant changes were observed for the other biomarkers, and there was no evidence of effect modification by key baseline characteristics across all biomarkers studied. In UK HARP-III, sacubitril/valsartan reduced urinary NGAL compared with irbesartan but did not affect other tubular biomarkers of injury, ischemia and fibrosis, suggesting limited tubular benefits, consistent with no observed effect on kidney function.

The hippocampus is a brain region critically involved in learning and memory and is particularly vulnerable to metabolic and inflammatory stresses. Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is associated with cognitive decline and structural alterations in the hippocampus, a condition commonly referred to as diabetic encephalopathy (DE). Lipocalin-2 (LCN-2), an acute-phase glycoprotein involved in iron homeostasis and innate immunity, has emerged as an important mediator of neuroinflammation and glial reactivity in the central nervous system. Although LCN-2 has been implicated in several neurodegenerative disorders, its region-specific role in hippocampal dysfunction during T2DM remains incompletely understood. Unlike prior reviews that address DE broadly, the present review synthesizes current experimental and clinical evidence linking hippocampal LCN-2 to neuroinflammation, synaptic dysfunction, and cognitive impairment in T2DM, with particular emphasis on astrocyte-microglia crosstalk. We further discuss the potential therapeutic strategy of selectively modulating LCN-2 signaling as an alternative to broad anti-inflammatory approaches, along with its potential advantages and limitations.

Objective Gestational diabetes mellitus (GDM) refers to glucose intolerance, insulin sensitivity, and beta islet cell dysfunction during pregnancy. GDM pathogenesis is associated with hypertension, impaired placental and renal function, oxidative stress, and increased circulating CD4+ T cells. There are limited animal models to explore GDM pathology and treatment. This study sought to determine a role for GDM placental CD4+ T cells to parallel manifestations of the GDM phenotype in pregnant athymic nude rats. Methods GDM placental CD4+ T cells (GDM T cells) were isolated upon delivery and injected into pregnant nude rats on gestational day (GD) 12. Mean arterial pressure and markers of renal injury, proteinuria, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin, were assessed on GD19. Glucose, insulin tolerance, and glucose tolerance tests were also performed. Renal and pancreatic tissues were stained using Periodic acid Schiff and hematoxylin and eosin, respectively. A one-way ANOVA was used for statistical analysis. Results Adoptive transfer of GDMT cells increased blood pressure (120.8 ± 2.2 mmHg, p < 0.05) compared to controls (105.4 ± 2.8 mmHg) and normotensive Tcell recipients (96.3 ± 3.9 mmHg). Metformin or MitoTEMPO attenuated this response. GDM T cell recipients had elevated blood glucose (p < 0.05) and impaired glucose tolerance and insulin sensitivity, which improved with metformin or MitoTEMPO treatment. Renal injury was more severe in GDM T cell recipients, but attenuated with metformin or MitoTEMPO. Pancreatic morphology showed reduced beta islet numbers in GDM T cell recipients. Conclusion GDM CD4+ T cells contribute to hypertension, glucose intolerance, and renal dysfunction, improved byMitoTEMPO. These findings supports optional therapeutics that support mitochondrial function during pregnancy.

Urinary neutrophil Gelatinase-Associated lipocalin as an early and reliable biomarker of diabetic nephropathy in type 2 diabetes mellitus.

Lipocalin-2 links spinal cord injury to neurogenic lung injury through MAPK/ERK-ferroptosis signaling: Preliminary evidence for a spinal cord-lung axis.

Patients admitted to the emergency department, the intensive care unit (ICU), and after cardiac surgery are at increased risk of developing adverse kidney events. Assessment of neutrophil gelatinase-associated lipocalin (NGAL) may facilitate renal risk prediction. However, the difference in NGAL-concentrations at admission in patients developing and not developing adverse events is unclear. An ancillary meta-analysis to a previous systematic review and meta-analysis using reanalyzed individual study-data from prospective clinical studies to compare NGAL concentrations measured using clinical laboratory platforms at patient admission. The study followed the Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data guideline. Studies of adults investigating acute kidney injury (AKI) of all stages, severe AKI (stage injury or failure), and acute initiation of renal replacement therapy (RRT) in the setting of cardiac surgery, emergency department, or intensive care unit using either urinary or plasma NGAL concentrations measured on clinical laboratory platforms. Data inclusion was limited to the individual study-level data from the predecessor study. This study used individual study-level data acquired using the protocol of a previous study, which was accomplished by individual authors' reassessment of their study data. Classification of AKI was harmonized among studies. Prespecified data comparison was performed for urine and plasma specimens for the outcome measures AKI, severe AKI, and acute RRT-initiation. Random effects meta-analyses were performed using the inverse variance method and the DerSimonian and Laird heterogeneity estimator. In total, 30 data sets from 26 studies were included. The estimated mean difference of urine NGAL concentrations was 125 (95% CI, 57.33-193.54) ng/mL for AKI, 317 (95% CI, 134.95-499.82) ng/mL for severe AKI, and 331 (95% CI, 71.36-592.06) ng/mL for RRT. For plasma NGAL concentrations, the estimated mean differences were 86.04 (95% CI, 51.74-120.34) ng/mL for AKI, 150.52 (95% CI, 80.27-220.76) ng/mL for severe AKI, and 129.83 (95% CI, 79.03-180.63) ng/mL for RRT. There were subgroup differences for the clinical setting, but not for the use of the urine output criterion. Multiple studies showed elevated NGAL concentrations in patients without serum creatinine concentration-based AKI, likely identifying patients with suspected AKI stage 1S (subclinical AKI). Imperfect harmonization of data across studies because of their original protocols. NGAL concentration differences may facilitate identification of patients at risk of AKI or with suspected AKI stage 1S at admission. Heterogeneity and variability across studies, specimen types, and settings emphasize the importance of interpreting NGAL values within the specific clinical context and patient population. The International Database of Prospectively Registered Systematic Reviews reg. no.: CRD42016042735. Version of Record 1.2.

Aging is associated with a decline in kidney function and increased susceptibility to renal injury and fibrosis. Several factors contribute to age-related structural changes and functional decline in the kidney. Time-restricted feeding (TRF) has potential anti-aging properties, but its effect on kidney health is unclear. The objective of this study is to determine the impact of TRF on kidney function and health in aged mice. We hypothesize that TRF will improve markers of kidney function and injury in aged mice compared with ad libitum (AL) age-matched mice. Male C57BL/6 mice, aged 6 and 18 months, were fed an AL high-salt diet (4.0% NaCl). A subset of aged mice was placed on a TRF schedule (8-hour feeding window during the active period) for five weeks. Tissues were collected at the beginning of the inactive period of the mice at the end of the feeding schedule. Immunohistochemistry was performed to assess the structural integrity of glomeruli. Daily food intake and activity levels were similar between AL and TRF groups in aged mice (N=5-6). Renal injury biomarkers kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed using multiplex immunoassay and immunoblotting, respectively. Cortical KIM-1 levels were higher in TRF mice compared to AL (P=0.05). Cortical KIM-1 concentration was also higher in aged mice compared to the young (P=0.0002; young AL: 17 ± 3; aged AL: 106 ± 15; aged TRF: 202 ± 39 pg/mL/protein; N=5-6). Medullary KIM-1 levels following TRF were similar to AL in aged mice (P=NS); however, KIM-1 increased in aged mice compared to young (P=0.001). Medullary NGAL expression was similar following TRF in aged mice and in aged vs young mice (P=NS). Similarly, there was no effect of TRF or age on serum creatinine and blood urea nitrogen levels (P=NS). Nephrin staining was used to assess glomeruli count and area. Glomerular quantity was not affected by TRF or age (P=NS; N=5-6). Glomerular size was similar following TRF compared to AL in aged mice (P=NS). Aged AL mice had larger glomeruli on average than young mice (P=0.04; young AL: 244 ± 18; aged AL: 318 ± 27; aged TRF: 279 ± 20 pixels/glomerular number; N=5-6). In conclusion, aging led to increased levels of particular kidney injury markers in mice on a high salt diet. However, TRF did not improve any of these markers in aged mice. Interestingly, KIM-1 was higher following TRF in aged mice. Future studies will determine the causes of this increase and whether kidney function is affected in response to TRF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

DNA-engineered immunosensing platform for ultrasensitive detection of clinical protein biomarkers.