Lipocalin-2 Levels Research Articles

Preliminary evidence of immune infiltration and neutrophil degranulation in peripheral blood of non-obese OSA patients related to cognitive decline

Obstructive sleep apnea (OSA) patients have varying degrees of cognitive impairment, but the specific pathogenic mechanism is still unclear. Meanwhile, poor compliance with continuous positive airway pressure (CPAP) in OSA prompts better solutions. This study aimed to identify differentially expressed genes between the non-obese OSA patients and healthy controls, and to explore potential biomarkers associated with cognitive impairment. Cohorts of healthy control (n = 20) and non-obese, treatment-naïve OSA patients (n = 20) were recruited. We collected their peripheral blood mononuclear cells and neutrophils, and their cognitive performances were evaluated by the Montreal Cognitive Assessment (MoCA). The differentially expressed genes were identified by bioinformatic analysis and confirmed by PCR. Imbalanced immune cell proportions were assessed by Cibersort. Biomarkers related to enriched cellular pathways were measured by ELISA. OSA patients showed a significant decline in overall cognitive function and were associated with higher daytime sleepiness scores. Multiple signaling pathways were enriched in the non-obese OSA cohort, including upregulation of neutrophil-degranulation. Increased monocyte proportion and decreased NK cell proportion were figured out. The relevant genes, including upregulated defensin alpha 4 (DEFA4), haptoglobin (HP), survivin (BIRC5), and suppressed interferon gamma (IFNG) expression were detected. The relative expression of DEFA4 was significantly correlated with the MoCA score and sleep parameters. Biomarkers such as myeloperoxidase (MPO), H2O2, and lipocalin-2, as representatives of neutrophils’ activation, elevated significantly in the OSA group. The data demonstrated a positive correlation between MPO and oxygen desaturation index (ODI) and a negative correlation between MPO and lowest oxygen saturation (LSaO2). The level of Lipocalin-2 was positively correlated with apnea-hypopnea index (AHI) and ODI and negatively correlated with LSaO2 and MoCA score. We also observed a negative correlation between H2O2 and mean oxygen saturation (MSaO2). Degranulation of neutrophils was activated in non-obese OSA patients without other complications. The process is related to OSA severity and cognitive impairment, implying its role in pathogenesis.

Elevated Fecal Lipocalin-2 Levels During Early Life Are Associated with Maternal Inflammatory Bowel Disease Diagnosis.

Fecal lipocalin-2 (LCN2) is a biomarker of neutrophil activation, which is elevated in patients with inflammatory bowel disease (IBD); however, its dynamic changes during pregnancy and early life are largely unknown. We characterized LCN2 levels by maternal IBD diagnosis, offspring feeding behavior, and gut microbiota composition. In the prospective MECONIUM (Exploring Mechanisms of Disease Transmission In Utero through the Microbiome) study, we analyzed 559 fecal samples from 91 pregnant women with IBD, 78 healthy controls, and their 147 offspring for LCN2 levels at each trimester of pregnancy and multiple time points during early life using linear mixed-effects model and multiple logistic regression analyses. Gut microbiota community compositions were evaluated following 16S rRNA gene sequencing. IBD cases had higher LCN2 levels throughout pregnancy compared to controls. In offspring, significantly higher LCN2 was found in babies born to mothers with IBD, compared to those without IBD, at 3months, 1year, and 4years (all p < 0.03), with offspring LCN2 levels being predictive of maternal IBD case status with > 85% accuracy at ages 1 and 4. We also detected correlations between LCN2 levels and certain IBD-associated bacterial taxa in both mothers and babies. Exclusively breastfed babies had lower LCN2 in the first weeks of life compared to formula or mixed-fed counterparts. Babies born to mother with IBD had significantly higher LCN2 during early life compared to controls with exclusive breastfeeding impacting LCN2 levels early on. LCN2 levels correlated with IBD-associated microbial taxa in both mothers and babies. Future studies should identify the biological drivers and health-related consequences of elevated LCN2 during early childhood.

The lipocalin saga: Insights into its role in cancer-associated cachexia.

Cancer-associated cachexia (CAC) is a debilitating condition, observed in patients with advanced stages of cancer. It is marked by ongoing weight loss, weakness, and nutritional impairment. Lower tolerance of chemotherapeutic agents and radiation therapy makes it difficult to treat CAC. Anorexia is a significant contributor to worsening CAC. Anorexia can be found in the early or advanced stages of cancer. Anorexia in cancer patients arises from a confluence of factors. Tumor-related inflammatory cytokines can directly impact the gastrointestinal tract, leading to dysphagia and compromised gut function. Additionally, increased serotonin and hormonal disruptions lead to early satiety, suppressing appetite. Due to the complexities in the pathogenesis of the disease, identifying druggable targets is a challenge. Research is ongoing to identify novel targets for the treatment of this condition. Recent research suggests a potential link between elevated levels of Lipocalin 2 (LCN2) and cachexia in cancer patients. LCN2, a glycoprotein primarily released by neutrophils, is implicated in numerous illnesses, including skin disorders, cancer, atherosclerosis, and type 2 diabetes. LCN2 suppresses hunger by binding to the melanocortin-4 receptors. Several in vitro, in vivo, and clinical studies indicate the association between LCN2 levels and appetite suppression. Further research should be explored emphasizing the significance of well-crafted clinical trials to confirm LCN2's usefulness as a therapeutic target and its ability to help cancer patients who are suffering from the fatal hallmark of cachexia. This review explores LCN2's function in the multifaceted dynamics of CAC and anorexia.

Evaluation of the serum level of Lipocalin 2 in vitiligo.

Vitiligo is considered as depigmenting skin disorder where patches of skin losing their pigment. Lipocalin-2 (LCN2) is one of the Inflammatory adipokines that has a potential role in skin disorders and other inflammatory diseases as well. To measure the concentration level of LCN2 in vitiligo patients compared to healthy controls and to investigate its relation to disease activity and other clinical data to evaluate its role in the pathogenesis of the disease. Eighty individuals subdivided equally into two groups (vitiligo and controls) were enrolled in the study. The serum level of LCN2 was measured by ELISA where from all participants, a 5-mL venous blood was withdrawn in plain tube from each subject. There were high significant difference of LCN2 in serum between both groups where LCN2 was higher in vitiligo patients than than controls with mean and standard deviations of 399.2 ± 134.6 and 257.2 ± 42.5 respectively (p < 0.001). The level of LCN2 tended to increase in vitiligo patients with sudden onset than gradual patients showing a significant difference with p-value 0.030. Regarding the severity of the disease results showed that the level of LCN2 tended to increase in moderate and severe patients than mild but with no significant difference between the groups. LCN2 may play a vital role and a good marker for the early diagnosis and the pathogenesis of vitiligo disease.

Independent prognostic value of lipocalin-2 in congenital heart disease-associated pulmonary artery hypertension.

Timely and accurate evaluation of the patient's pulmonary arterial pressure (PAP) is of great significance for the treatment of congenital heart disease. Currently, there is no non-invasive gold standard method for evaluating PAP. To assess the prognostic value of lipocalin-2 (LCN2) in relation to PAP in patients with congenital heart disease associated with pulmonary artery hypertension. We conducted a retrospective analysis of 69 pediatric patients diagnosed with ventricular septal defects. The patients' clinical and laboratory data were collected. The serum LCN2 concentrations were compared between the pulmonary arterial hypertension (PAH) group and the nonPAH group. The correlation of LCN2 concentration with PAH classification was evaluated using binary logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic potential of LCN2 for PAH. Serum LCN2 concentration significantly correlated with patients' mean PAP (r = 0.544, P < 0.001), but not correlated with creatinine (P = 0.446) or blood urea nitrogen (P = 0.747). LCN2 levels were significantly correlated with PAH in both univariate [odds ratio (OR) 1.107, 95%CI: 1.033-1.185, P = 0.004)] and multivariate regression analysis (OR 1.150, 95%CI: 1.027-1.288, P = 0.015). ROC curve analysis revealed an area under the curve of 0.783 for LCN2. At the cutoff value of 19.42 ng/mL, the sensitivity and specificity of LCN2 for diagnosing PAH is 90.19% and 55.56%, respectively. LCN2 concentration also significantly correlated with the post-repair mean PAP in patients with congenital heart disease (r = 0.532, P = 0.009). LCN2 is emerging as a candidate biomarker for assessing PAP in patients with congenital heart disease. Its high sensitivity in diagnosing PAH makes it a valuable tool in patient management.

Circulating lipocalin-2 across the adult lifespan.

Lipocalin-2 (LCN2), a hormone produced by adipocytes, osteoblasts, and renal tubular cells, is implicated in age-related diseases, including cardio-metabolic disease. To understand the role LCN2 may play in pathological states, we first need to elucidate the relationship between circulating LCN2 with indices of cardio-metabolic health during "normal" aging. This study examined the relationship between serum levels of LCN2, age, and cardio-metabolic measures across the adult lifespan in males and females. We conducted a pooled cohort analysis including 124 community-dwelling males (n = 52) and females (n = 72) (age 20-87yr, median BMI 25.92 [23.04, 29.81] kg/m2). Serum LCN2 was analyzed using a two-step chemiluminescent microparticle monoclonal immunoassay. The relationship between LCN2 and age was evaluated by linear regression and cubic spline. Simple linear regressions were performed to investigate the relationship between LCN2 and the following variables: BMI, VO2peak, serum glucose, and body composition (DXA). For every 1yr increase in age, LCN2 levels were 0.26mg/L higher (P= .007, 95% CI [0.07, 0.45]). Each 1 unit increase in BMI (kg/m2) was associated with 0.88mg/L higher LCN2 levels (P= .027, [0.10, 1.66]) and each 1 unit increase in VO2peak (mL/kg/min) was associated with 0.38mg/L lower LCN2 (p= .003, [-0.63, -0.13]).There was no significant relationship between LCN2 and sex, glucose levels or body composition (all p> .05). LCN2 increased linearly across the adult lifespan while it decreased as fitness level increased. Future research should build on these findings to determine whether LCN2 can be used as a biomarker for chronic disease and if exercise can mitigate age-related disease associated with LCN2 changes.

Effect of Low- and Moderate-Intensity Aerobic Training on Body Composition Cardiorespiratory Functions, Biochemical Risk Factors and Adipokines in Morbid Obesity.

Obesity poses an enormous public health and economic burden worldwide. Visceral fat accumulation is associated with various metabolic and cardiovascular consequences, resulting in an increased prevalence of atherosclerotic conditions. We aimed to examine the impact of low-and moderate-intensity aerobic training on several anthropometric and cardiorespiratory parameters and markers of atherosclerosis, including inflammation, serum levels of lipoproteins and adipokines of extremely obese patients in poor condition. Forty severely obese patients were recruited and randomized into two groups, Group 1 and Group 2, for a six-week inpatient study. Group 1 received moderate-intensity (40-60% heart rate reserve) and Group 2 received low-intensity (30-39% of heart rate reserve) aerobic training combined with resistance training. The patients' cardiorespiratory functions were assessed by ergospirometry. Anthropometric data were recorded, body composition was analyzed and functional tests were performed. We also investigated serum lipids and high-sensitive C-reactive protein levels and calculated the homeostatic model assessment-insulin resistance indices and adipokine levels as predictive biomarkers. Functional abilities and some biochemical parameters, such as homeostatic model assessment-insulin resistance, serum lipids, apolipoprotein A and apolipoprotein-B improved in both groups in a positive direction. However, cardiorespiratory capacity and the serum levels of high-sensitive C-reactive protein and Lipocalin-2 decreased, while irisin and paraoxonase 1 increased significantly, but only in Group 1. Six weeks of aerobic training, regardless of its intensity, could induce favorable changes in functional tests, body composition and serum lipids, even in severely obese, extremely unconditioned patients in both groups. However, moderate-intensity aerobic training should at least increase cardiorespiratory capacity and yield a better lipid profile oxidative status and inflammation profile.

Diagnostic utility of lipocalin 2 and metalloproteinase 9 levels in early-stage endometrial cancer

Background Endometrial cancer (EC) is the fourth most common gynecologic malignancy among women. Histopathologic examination is considered gold-standard for diagnosis of EC. However, these examinations sometimes not be useful in distinguishing early stage types of EC. Objectıves The current study aimed to investigate the clinicopathological significance of Lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), and ferritin in tumor progression. Methods A total of 98 patients (55 women newly diagnosed with early-stage endometrial cancer [study group] and 43 women with benign endometrial pathologies [control group]) were enrolled. Results There was a significant difference between diagnosis (p &lt; 0.001), surgical procedure (p &lt; 0.001), pathology (p = 0.002), stage (p &lt; 0.001), lymphovascular invasion (LVI) (p = 0.002), myometrial invasion (p &lt; 0.001), and staining intensity (p &lt; 0.001), MMP9 (p = 0.023), LCN2 (p &lt; 0.001), glucocorticoid (GC) (p = 0.048), tumor necrosis factor-alpha (TNF-α) (p = 0.044), menopause duration (p = 0.001), body weight (p &lt; 0.001), and body mass index (BMI) (p &lt; 0.001) were found to be higher, and ferritin levels (p = 0.047) were lower in the endometrial adenocarcinoma group compared to the benign endometrial pathologies. Conclusıon LCN2, MMP9, and ferritin are practical markers in early cases of endometrial cancer. Serum LCN2 and MMP9 levels may be good clinical tools for the auxiliary diagnosis of early-stage endometrial cancer. Ferritin was also significantly sensitive. Therefore, detecting these markers together may be more beneficial for cancer diagnosis.

Lipocalin-2 as a marker of inflammation, bone density, and triglyceride-glucose index for new-onset arthritis patients in Mosul, Iraq.

Lipocalin-2 is an acute phase-associated adipokine that can serve as an inflammatory and biomarker indicator of cartilage deterioration in osteoarthritis. However, its role in the musculoskeletal system remains not fully understood. Hence, this study aimed to evaluate lipocalin-2 and its relationship with markers of inflammation (Interferon-gamma, ESR, and CRP), bone density (vitamin D3 and calcium), and the triglyceride-glucose index in new-onset arthritis patients in Mosul, Iraq. This study included 125 participants aged 20 to 65, divided into two groups. The Arthritis Patient Group comprised 70 participants (37 females and 33 males) attending the Bone Diseases Consultation Unit at the Ibn Sina Teaching Hospital in Mosul, Iraq. The Control Group comprised 31 females and 24 males. Ethical approval was obtained from the Iraqi Ministry of Health - Nineveh Health (No. 2022095). Commercial ELISA kits were used to measure serum lipocalin-2, Interferon-gamma, ESR, and CRP as inflammation markers, vitamin D3, and calcium as bone density markers. Moreover, the Triglyceride Glucose (TYG) Index was evaluated. The findings revealed a significant increase in lipocalin-2 levels in males compared to females, with LCN-2 increasing with age. Arthritis patients showed a significant increase (72%) in lipocalin-2 levels. Inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, interferon-gamma) displayed significant increases (46%, 1200%, and 581%, respectively). Glucose (23%), triglycerides (71%), and TYG index (21%) also exhibited significant increases. Meanwhile, bone density indicators (vitamin D3 and calcium) found a significant decrease (53% and 20%, respectively) in arthritis patients. Linear correlation coefficient (R) analysis revealed a significant positive relationship between lipocalin-2 and indicators of inflammation, glucose, TG, and TYG index. This study's findings suggest that LCN-2 serum levels were higher in patients with new-onset arthritis than in controls in Mosul, and LCN-2 serum increased in males compared with females and getting older serum LCN-2 increased for the patients and control groups. Furthermore, a significant correlation was found between the Triglyceride Glucose Index, which measures metabolic disorders, and serum LCN-2 levels and inflammatory indicators in new-onset arthritis patients in Mosul, Iraq.

A systematic review of the implications of lipocalin-2 expression in periodontal disease.

Evidence suggests that lipocalin-2 (LCN-2), a bone-derived protein, is upregulated in periodontal diseases. This systematic review aimed to evaluate LCN-2 concentrations in individuals with periodontal diseases, identifying the most suitable body fluids for its detection, the type of periodontal disease with the highest LCN-2 expression, its association with other inflammatory markers and systemic diseases, and whether its expression can be modified by periodontal treatment. A systematic search of Google Scholar, PubMed, and ProQuest up to August 2024 was conducted. The studies were screened and selected by the authors according to specific eligibility criteria. Quality assessment of the included studies was performed according to the study type using STROBE statement for observational studies or the modified Jadad scale for experimental studies. The review was registered in PROSPERO (CRD42023458565). In total, three thousand six hundred and thirty-eight reports were identified, of which twenty-seven were full-text assessed for eligibility, including eleven articles. Seven articles were observational, and four were experimental. Significantly elevated LCN-2 levels were reported in patients with periodontal disease across 9 studies, being higher in periodontitis rather than gingivitis. LCN-2 was mainly detected in gingival crevicular fluid (GCF) and saliva. LCN-2 expression is related to the increment of inflammatory markers, and periodontal therapy decreases LCN-2 concentrations. LCN-2 levels were aggravated when periodontitis was accompanied by obesity and type 2 diabetes. LCN-2 is implicated in periodontal diseases, probably through the inflammation process.

Diagnostic and prognostic value of plasma lipocalin-2 levels in patients with metabolic dysfunction–associated steatotic liver disease

Abstract Background Non-Alcoholic Fatty Liver Disease, recently better recognised as Metabolic Dysfunction–Associated Steatotic Liver Disease, is the most prevalent form of chronic liver disease at present time. It is estimated to impact 32% of the world's population, hence representing a significant health burden. Aim of the work To assess the significance of plasma Lipocalin-2 (LCN2) levels in the diagnosis and prognosis of NAFLD patients. Patients and methods In this retrospective case–control study we recruited 102 subjects aged between 18 and 70 years. The included participants were split into two study groups. Group I: 51 NAFLD patients (61% men, 39% females) and Group II: 51 healthy controls (51% men and 49% females), for whom plasma LCN2 levels were assessed and correlated with NAFLD fibrosis score, FIB4 and fatty liver index. Results In this study, LCN2 levels in NAFLD patients were significantly greater compared to individuals in the control group (p &lt; 0.001), with a mean of 1893.214 ± 1002.852 ng/dL in the cases and a mean of 466.020 ± 397.699 ng/dL in the controls. This suggests the use of LCN2 as a possible diagnostic marker of NAFLD. The mean LCN2 levels in this study also significantly increased as the grade of fatty liver increased from I to III (p &lt; 0.001). This in turn proposes the use of LCN2 as a prognostic marker for NAFLD progression. LCN2 also significantly correlated with the fatty liver index and NAFLD Fibrosis scoring systems, but not with Fib-4. With an area under the ROC of 0.906, it demonstrated excellent diagnostic performance with 84% sensitivity, 90% specificity, 89.6% PPV and 85.2% NPV for the prediction of NAFLD patients. Conclusion Lipocalin-2 performs as a diagnostic and a possible prognostic marker for metabolic dysfunction-associated steatotic liver disease.

Associations between plasma markers and symptoms of anxiety and depression in patients with breast cancer

Background and purposeAmong patients with solid tumors, those with breast cancer (BC) experience the most severe psychological issues, exhibiting a high global prevalence of depression that negatively impacts prognosis. Depression can be easily missed, and clinical markers for its diagnosis are lacking. Therefore, this study in order to investigate the diagnostic markers for BC patients with depression and anxiety and explore the specific changes of metabolism.Method and resultsThirty-eight BC patients and thirty-six matched healthy controls were included in the study. The anxiety and depression symptoms of the participants were evaluated by the 17-item Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA). Plasma levels of glial fibrillary acidic protein (GFAP) and lipocalin-2 (LCN2) were evaluated using enzyme linked immunosorbent assay, and plasma lactate levels and metabolic characteristics were analyzed.ConclusionThis study revealed that GFAP and LCN2 may be good diagnostic markers for anxiety or depression in patients with BC and that plasma lactate levels are also a good diagnostic marker for anxiety. In addition, specific changes in metabolism in patients with BC were preliminarily explored.

Effects of neutrophilic granule protein on the expression of lipocalin 2 in inflammatory macrophages

To explore the effects of neutrophilic granule protein (NGP) on the expression of lipocalin 2 (LCN2) in inflammatory macrophages and its mechanism. NGP-high-expressed RAW264.7 cells (NGP/RAW cells) and negative control RAW264.7 cells (NC/RAW cells) were cultured in vitro. Primary peritoneal macrophages of NGP-high-expressed mice and wild-type C57BL/6 mice were extracted, then cultured in vitro. The cell inflammatory model was established by stimulating with 10 mg/L lipopolysaccharide (LPS, LPS group), and the phosphate buffer solution (PBS) control group was set up. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of LCN2 in different types of cells. The protein expression of phosphorylated signal transduction and activator of transcription 1 (p-STAT1) was detected with Western blotting. Other NGP/RAW cells and NC/RAW cells were treated with 10 mg/L LPS, 5 mg/L STAT1 pathway inhibitor (fludarabine)+10 mg/L LPS, respectively. The PBS control group was set up. ELISA was used to detect the level of LCN2. In different types of cells, the levels of LCN2 were increased significantly after LPS stimulation in the LPS group as compared with those in the PBS control group, and peaked at 24 hours (μmol/L: 25.61±1.02 vs. 0.46±0.02 in NC/RAW cells, 74.51±2.14 vs. 0.25±0.04 in NGP/RAW cells, 10.13±0.22 vs. 0.01±0.01 in primary macrophages of wild-type C57BL/6 mice, 28.35±0.61 vs. 0.08±0.01 in primary macrophages of NGP-high-expressed mice, all P < 0.05), indicating that the expression of LCN2 in macrophages altered during inflammation reaction. The level of LCN2 in NGP/RAW cells was found significantly increased at different time points after LPS stimulation comparing with that in NC/RAW cells (μmol/L: 8.32±0.22 vs. 3.12±0.11 at 6 hours, 23.12±0.86 vs. 8.12±0.32 at 12 hours, 74.51±2.14 vs. 25.61±1.02 at 24 hours, all P < 0.05), along with the expression of p-STAT1 was significantly up-regulated. The level of LCN2 in the primary macrophages of NGP-high-expressed mice was also significantly increased at 24 hours after LPS stimulation comparing with that in the primary macrophages of wild-type C57BL/6 mice (μmol/L: 28.35±0.61 vs. 10.13±0.22, P < 0.05). However, after pretreated with STAT1 pathway inhibitors, the production of LCN2 in NGP/RAW cells was decreased significantly comparing with that in the LPS group (μmol/L: 6.81±0.19 vs. 22.54±0.58, P < 0.05). But the inhibitors had no significant effect on LCN2 production in NC/RAW cells showing no significant difference as compared with LPS group (μmol/L: 8.04±0.20 vs. 7.86±0.15, P > 0.05), indicating that NGP could up-regulate the expression of LCN2 in macrophages stimulated by LPS by promoting STAT1 activation. NGP could positively regulate LCN2 expression in inflammatory macrophages by activating STAT1 pathway.

The Role of Nitric Oxide, Lipocalin-2, and Proinflammatory Cytokines on Proteinuria and Insulin Resistance in Type 2 Diabetes Mellitus Subgroups.

Nitric oxide (NO) is a bioactive signaling molecule that mediates various physiological and biological processes. Type 2 diabetes mellitus (T2DM) can be categorized into several subgroups according to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) levels. Few studies have closely examined the effect of NO and lipocalin-2 on albuminuria and insulin resistance in T2DM subgroups. This study investigated the role of NO, lipocalin-2, and proinflammatory cytokines on the development of proteinuria and insulin resistance in patients with T2DM subgroups. A total of 256 subjects, including 191 patients with T2DM and 65 non-diabetic healthy individuals, were evaluated. NO metabolites (NOx), lipocalin-2, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured. Patients with T2DM were classified into three subgroups: patients with FPG-defined diabetes (PG-DM), those with HbA1c-defined diabetes (HA-DM), and those who met the criteria for both FPG and HbA1c (PG/HA-DM). The albumin-to-creatinine ratio (ACR) and the homeostasis model assessment of β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated. NOx, lipocalin-2, and TNF-α levels were significantly higher in patients with T2DM than in healthy individuals. Patients with PG/HA-DM had significantly higher NOx levels than those with PG-DM or HA-DM. Of the patients with high NOx levels, patients with lipocalin-2 elevation exhibited higher ACR and HOMA-IR than those without lipocalin-2 elevation. NOx was positively correlated with lipocalin-2, ACR, HOMA-IR, and TNF-α but not with HOMA-B and IL-6. The upper quartile of NOx levels led to a 1.2-fold increase in the risk of albuminuria (odds ratio: 1.215; 95% CI: 1.012-2.418; p < 0.001). NO plays a crucial role in proteinuria and insulin resistance by collaborating with lipocalin-2 and TNF-α, showing significantly higher levels in patients with PG/HA-DM than in those with PG-DM or HA-DM.

GDF15 and LCN2 for early detection and prognosis of pancreatic cancer

BackgroundThe prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain. MethodsCirculating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated. FindingsOur results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity. InterpretationOur findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.

Defining age-specific reference intervals for biomarkers distinguishing bacterial from viral infection in paediatrics

Differentiating bacterial from viral infections in children is a common clinical challenge. Novel host immune biomarkers have the potential to aid thediagnosis of infection aetiology and identify children who require antibiotics. Data on novel infection biomarkers gender and age-specific correlations, and reference intervals in healthy paediatrics is lacking. This study reports the plasma levels of three novel biomarkers that can aid in the differentiation of bacterial and viral infection in a healthy group of paediatrics. The levels of (Interferon-Gamma Inducible Protein 10 kDa (IP-10), Lipocalin-2 (LCN2) and TNF-Related Apoptosis-Inducing Ligand (TRAIL) were quantified in 199 plasma samples from healthy paediatrics aged 2 to 16 years old from across the UK. Reference intervals (2.5th and 97.5th) were determined, and biomarker levels were examined for sex and age associations. Reference intervals for IP-10, LCN2 and TRAIL for ages 2–16 years were 36.7–168.1 pg/ml, 14.2–123.3 ng/ml, 57.4–71.4 pg/ml respectively. No biomarker showed an association with sex and IP-10 did not show any association with age. TRAIL levels had a weak continuous negative correlation with age and LCN2 levels had a continuous positive correlation with age. Specific cut-offs for LCN2 in two age categories were identified, while TRAIL did not require age partitions. This study provides age-appropriate reference intervals for three biomarkers of infection in healthy children. These findings have the potential to improve the impact of future research on these biomarkers, the accuracy of clinical decision-making in children with infection, paediatric patient care and outcomes, and antimicrobial stewardship.

Lipocalin-2 as a fundamental protein in type 2 diabetes and periodontitis in mice.

Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility. A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA. Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic β cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur. LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic β-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture. In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.

Aloe-emodin alleviates inflammatory bowel disease in mice by modulating intestinal microbiome homeostasis via the IL-4/IL-13 axis

IntroductionInflammatory bowel disease (IBD) is a global health concern. Aloe-emodin (AE) has diverse pharmacological benefits, including anti-inflammatory effects. However, its role in IBD remains unclear, prompting our investigation of its regulatory effects and mechanisms in an IBD mouse model. MethodsWe studied the therapeutic efficacy of AE in alleviating symptoms and modulating cytokine secretion in a murine model of dextran sulfate sodium (DSS)-induced colitis. BALB/c mice were administered DSS to induce colitis and were subsequently treated with varying doses of AE. Changes in body weight, fecal lipocalin-2 (LCN2) levels, colon tissue histology, and serum cytokine concentrations were evaluated to assess the effects of AE treatment. Additionally, 16 S rRNA sequencing was used to analyze alterations in the composition of the gut microbiota following AE intervention. Finally, the database was used to analyze the signaling pathways associated with IBD in AE and to detect the expression levels of interleukin (IL)-4 pathway using real-time quantitative reverse transcription PCR. Exogenous IL-4 was used in rescue experiments to observe its effects on the disease process of IBD under AE regulation. ResultsAE treatment resulted in a dose-dependent mitigation of weight loss, reduction in fecal LCN2 levels, and amelioration of histological damage in DSS-induced colitis in mice. The levels of superoxide dismutase and catalase increased, whereas malondialdehyde decreased following AE treatment, indicating a dose-dependent alleviation of colitis symptoms. Furthermore, AE administration attenuated the secretion of pro-inflammatory cytokines, including IL-17, tumor necrosis factor-alpha (TNF-α), and chemokine ligand 1, while promoting the expression of anti-inflammatory cytokines IL-4 and IL-13. Analysis of the gut microbiota revealed that AE effectively suppressed the overgrowth of colitis-associated bacterial species and restored microbial homeostasis. Finally, we found that overexpression of IL-4 was able to reverse the therapeutic effect of AE for DSS-induced IBD. ConclusionAE shows promise in alleviating colitis severity, influencing inflammatory cytokines, and modulating the gut microbiota in an IBD mouse model via the IL-4/IL-13 pathway, suggesting its potential as a natural IBD remedy.

Lipocalin-2 Level in Patients with Polycystic Ovary Syndrome: Association with Insulin Resistance and Metformin Therapy

Abstract Background PCOS appears to be associated with an increased risk of metabolic aberrations, including insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease throughout womens’ lifespan. Aim of the Work The aim of this study is to: Assess the association of Lipocalin-2 with polycystic ovary syndrome in a sample of the Egyptian female. Study the effect of metformin therapy on Lipocalin-2 level in female patients with polycystic ovary syndrome Patients and Methods Our study was conducted on 52 females. Their age ranged between 17-43 years old. They were collected from the outpatient obstetrics and gynaecology clinics of Ain Shams University Hospitals, assess the association of Lipocalin-2 with polycystic ovary syndrome in a sample of Egyptian females and its association with insulin resistance. It was conducted from June 2018 to March 2019. The study was explained to all patients and control subjects, and written consent was obtained before starting the study. Results Serum lipocalin-2 levels did not differ between patients with PCOS and BMI-matched healthy controls (P-value 0.193). In the present study, there was no significant difference between the 2 studied groups as regard HOMA-IR (p = 0.375). Metformin therapy for 3 months in patients with PCOS in the present study, resulted in significant reduction in lipocalin-2 level (p- value&amp;lt;0.01), (mean 54.2±15.3 ng/ml before metformin therapy vs 42.9±14.2 ng/ml after metformin therapy). In our study metformin therapy in PCOS group resulted in significant reduction in weight, BMI, waist circumference and HOMA-IR. Furthermore, linear regression analysis for the parameters affecting lipocalin level in our study, showed that BMI was the only significant confounder affecting lipocalin level. So the reduction in lipocalin level following metformin therapy in PCOS group in our study may be due to weight reduction perse. Conclusion In conclusion, our results show that PCOS per se is not associated with elevated serum lipocalin-2 levels. Weight loss induces a significant reduction in serum lipocalin-2 levels in overweight/obese patients with PCOS. Treatment with metformin of patients with PCOS also induces a reduction in serum lipocalin-2 levels.

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.