Serum Lipocalin-2 Research Articles

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.

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<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.

Serum Lipocalin-2 Levels as a Biomarker in Pre- and Post-Pubertal Klinefelter Syndrome Patients: A Pilot Study.

Klinefelter syndrome (KS) is a male genetic disease caused by the presence of an extra X chromosome, causing endocrine disorders mainly responsible for a high rate of infertility and metabolic disorders in adulthood. Scientific research is interested in identifying new biomarkers that can be predictive or prognostic of alterations strictly connected to KS. Lipocalin-2 (LCN-2, also known as NGAL) is a small protein initially identified within neutrophils as a protein related to innate immunity. Serum LCN-2 estimation seems to be a useful tool in predicting the metabolic complications caused by several pathological conditions. However, little is known about its potential role in infertility conditions. The present pilot study aims to investigate the presence of LCN-2 in the serum of a group of pre-pubertal and post-pubertal children affected by KS, compared to healthy controls. We demonstrated for the first time the presence of elevated levels of LCN-2 in the serum of KS patients, compared to controls. This increase was accompanied, in pre-pubertal KS patients, by the loss of correlation with LH and HDL, which instead was present in the healthy individuals. Moreover, in all KS individuals, a positive correlation between LCN-2 and inhibin B serum concentration was found. Despite the limited size of the sample analyzed, our preliminary data encourage further studies to confirm the findings and to extend the study to KS adult patients, to verify the predictive/prognostic value of LCN-2 as new biomarker for metabolic diseases and infertility associated with the pathology.

P130 High serum lipocalin-2 expression at the diagnosis in children with ulcerative colitis: a pilot study

Abstract Background The identification of new biomarker is a main challenge in inflammatory boweldisease. Lipocalin-2 (LCN-2) is a pleiotropic mediator of various inflammatory processes. We determined the serum levels of LCN-2 in a cohort of newly diagnosed UC children, and we compared them with healthy controls. Methods Prospective cross-sectional observational study conducted at the Pediatric Gastroenterology, hepatology, and nutrition Unit of the Umberto I Hospital in Rome and at the IBBC – Institute of Biochemistry and Cell Biology – CNR in Rome. All children aged 6-18 years of age, newly diagnosed with UC at the Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, were consecutively enrolled. Blood withdrawal was conducted upon diagnosis. Human serum LCN-2 (Cat. No. DY1757) was measured using a sandwich enzyme-linked-immunosorbent assay (ELISA) kits (R&D Systems, Minneapolis, MN, USA), according to the protocols provided by the manufacturer. Clinical, demographic, biochemical and endoscopic data were recorded. Results Thirty-two children with a new diagnosis of UC [11 (34%) female, mean age 12,7 ± 4] and 38 age- and sex-matched healthy control [21 (55%) females, mean age 11.71 ± 4] were consecutively enrolled. Serum LCN-2 levels were significantly higher in cases compared to controls (280 ± 152 ng/mL vs 66 ± 55 ng/mL), p < 0,001]. Among UC children, significantly higher LCN2 levels were measured in pancolitis (363.7± 155.2 ng/mL) compared to proctitis, left-sided and extensive colitis (184.9 ± 74.65 ng/mL; p = 0.0003). A significant inverse correlation was observed between LCN-2 and albumin levels at the diagnosis by the Spearman coefficient correlation (r = −0.455; P = 0.03) and a significant direct correlation was observed between LCN-2 and CRP values at the diagnosis (r = 0.44; p <0.05). Conclusion Serum LCN-2 levels are significantly higher in children with UC compared to the healthy control group, with the highest levels observed in children with the most extensive disease. Such results as well as and its correlation with the actual disease monitoring tool, make this protein an interesting candidate biomarker.

Serum Lipocalin-2 in Patients with Psoriasis Vulgaris in Relation to Itching and Psoriasis Severity

Serum Lipocalin-2 in Patients with Psoriasis Vulgaris in Relation to Itching and Psoriasis Severity

Lipocalin-2 Serum Levels in Rheumatoid Arthritis Patients Treated with Adalimumab and Its Correlation with Proinflammatory Factors.

Obesity is associated with an increased risk for different chronic diseases such as osteoarthritis (OA) or rheumatoid arthritis (RA). In fact, adipose tissue is now recognized as an endocrine organ able to secrete a wide variety of factors called adipokines, which have been demonstrated to participate in the pathophysiology of RA by regulating inflammation and immunity. LCN2 is one of these adipose tissue-derived factors. However, scarce information is available about the levels of this adipokine in different rheumatic diseases. Therefore, we aimed to analyze LCN2 serum levels in healthy, OA, and RA patients under different treatments. Serum levels of LCN2, among other proinflammatory and chemotactic factors, have been measured by ELISA or Multiplex in the following four groups of individuals: healthy, OA, and RA patients treated with conventional treatment or adalimumab. We found increased serum levels of LCN2 in OA and RA patients. Interestingly, LCN2 serum levels show a similar pattern to that observed for different proinflammatory and chemotactic factors, being increased in RA conventional treated patients in comparison to RA patients treated with adalimumab. Also, RA patients under conventional treatment revealed a positive and significant correlation between LCN2 and CCL2, CCL3, IL-8, IL-1β, IL-6, and CRP. In patients with RA treated with adalimumab, only IL-6 and CRP correlated significantly with LCN2. Our results clearly suggest that LCN2 is modulated and associated with inflammation in rheumatic diseases. Therefore, the serum levels of this adipokine might be used as an additional biomarker of the inflammatory/disease activity.

Altered IL-3 and lipocalin-2 levels are associated with the pathophysiology of major depressive disorder: a case-control study

BackgroundMajor Depressive Disorder (MDD) is a common mental ailment and is the primary reason for disability. It manifests a severe impact on moods, thoughts, and physical health. At present, this disorder has become a concern in the field of public health. Alteration of neurochemicals is thought to be involved in the pathogenesis of many psychiatric disorders. Therefore, we aimed to evaluate serum IL-3 and lipocalin-2 in MDD patients and healthy controls (HCs).MethodWe included a total of 376 participants in this study. Among them, 196 were MDD patients, and 180 were age-sex-matched HCs. MDD patients were recruited from the Psychiatry Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), but the controls were from different parts of Dhaka. All study participants were evaluated by a psychiatrist using the DSM-5 criteria. To assess the severity of the depression, we used the Hamilton depression (Ham-D) rating scale. Serum IL-3 and lipocalin-2 levels were measured using commercially available enzyme-linked immune-sorbent assay kits (ELISA kits).ResultsAccording to this study, we observed elevated serum levels of IL-3 (1,024.73 ± 29.84 pg/mL) and reduced levels of serum lipocalin-2 (29.019 ± 2.073 ng/mL) in MDD patients compared to HCs (911.11 ± 20.55 pg/mL and 48.065 ± 3.583 ng/mL, respectively). No associations between serum levels of IL-3 and lipocalin-2 and depression severity were observed in patients.ConclusionsAccording to the present findings, alterations of serum IL-3 and lipocalin might be associated with the pathogenesis of MDD. These results support that altered serum neurochemicals can serve as early risk assessment markers for depression. Further interventional studies are recommended for a better understanding of the role of IL-3 and lipocalin-2 in the pathophysiology of depression.

Hemorrhagic Fever with Renal Syndrome Patients Exhibit Increased Levels of Lipocalin-2, Endothelin-1 and NT-proBNP.

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by viruses of the Orthohantavirus genus. This syndrome is characterized by renal and cardiopulmonary implications detectable with different biomarkers. Here, we explored the role of serum and urine levels of lipocalin-2, endothelin-1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in HFRS pathology. A total of twenty-eight patients hospitalized due to a Puumala orthohantavirus infection were included, with serum and urine samples collected on patient admission (acute phase) and discharge (convalescent phase). In comparison to healthy individuals, patients exhibited significantly higher acute-phase serum and urine levels of lipocalin-2, serum levels of endothelin-1 and serum and urine levels of NT-proBNP. Patients in the convalescent phase showed a significant decrease in urine lipocalin-2, serum endothelin-1 and serum and urine NT-proBNP levels. We recorded a strong correlation between serum levels of lipocalin-2 and endothelin-1 and urine levels of lipocalin-2 with several kidney injury markers, such as serum creatinine, urea, urine white blood cell count and proteinuria. We also demonstrated an independent correlation of serum and urine lipocalin-2 levels with acute kidney injury in HFRS. All in all, our results show an involvement of NT-proBNP, lipocalin-2 and endothelin-1 in the renal and cardiac pathology of HFRS.

ЛИПОКАЛИН СЫВОРОТКИ КРОВИ БОЛЬНЫХ ОСТРЫМ ПАНКРЕАТИТОМ

Abstract. Introduction. Acute pancreatitis is a severe inflammatory disease of the pancreas. In case of severe acute pancreatitis, mortality rate reaches 36-50%. The most challenging issue is the prediction of its severity and clinical outcome due to the limitations of clinical scoring systems and biochemical markers, which are still being studied intensely. Aim: To study serum lipocalin levels in patients with acute pancreatitis of varying severity. Materials and Methods. Our study included 68 patients diagnosed with acute pancreatitis and treated in the inpatient facility of Kazan City Clinical Hospital 7 over the years 2017-2019. Patients were stratified by severity, gender, and age. As a comparison group, 20 healthy volunteers without any gastrointestinal issues were examined. Specimen to be studied were the sera of patients with acute pancreatitis and those of healthy volunteers. Blood was sampled from the patients upon admission to the hospital and before their discharge from it. Lipocalin levels were registered using BioVendor’s Human Lipocalin-2/NGAL ELISA kit. The findings were processed statistically at their normal distribution. Results and Discussion. Our study showed a significant excess of lipocalin levels in patients with acute pancreatitis as compared with healthy volunteers. In healthy volunteers this value varied within 4.91±6.55 ng/ml, while it was 78.19±89.09 ng/ml (p<0.05) in acute pancreatitis patients. Conclusions. Our study of serum lipocalin in patients with acute pancreatitis showed a significant and statistically reliable excess of this indicator as compared to healthy volunteers. The highest lipocalin levels were found in patients with severe acute pancreatitis. Conventional therapy reduced these levels in mild, moderate, and severe cases, although there was no statistically significant difference before and after treatment. Keywords: pancreatic necrosis, lipocalin, prediction.

Serum and Tissue Lipocalin-2 Expression in Chronic Kidney Disease Pruritic Patients.

Uremic pruritus is an irritating symptom for patients with end-stage kidney disease. Lipocalin-2 (LCN2) has relevant importance in several biological cellular processes and immunity. It is also a major player in the progression of many disorders, such as renal injury. To evaluate LCN2 expression in chronic kidney disease (CKD) pruritic patients in serum together with immunohistochemical expression in skin samples and further correlation of their results with the studied clinicopathologic parameters. Serum level of LCN2 (assessed by enzyme-linked immunosorbent assay) and skin immunohistochemical expression were investigated in 25 CKD patients and 25 healthy controls. Ten patients were subjected to narrowband ultraviolet B phototherapy for 12 weeks then re-evaluated for serum and tissue LCN2 after therapy. LCN2 expression was increased significantly in both the epidermis and dermal adnexa in CKD patients over controls. Also, serum LCN2 level was higher in patients than in healthy subjects and was significantly associated with itching severity, grades of CKD, urea, and creatinine serum level. Tissue and serum levels of LCN2 were significantly diminished in CKD patients following narrowband therapy along with improvement of the severity of pruritus. The increased serum and tissue LCN2 expression in CKD pruritic patients and its pronounced decrease, in addition to the improvement of pruritus after treatment, suggest a major pathogenic role of LCN2 in uremic pruritus.

Evaluation of Serum Lipocalin-2 Level and Its Relation to Insulin Resistance in Patients with Inflammatory Acne Vulgaris

Abstract Introduction Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit. It is characterized by the formation of non-inflammatory comedones and inflammatory papules, pustules, nodules and cysts. Lipocalin-2 (LCN2) is an attractive biomarker of inflammation, ischemia, infection, and kidney damage. Aim of the Study The current study aimed to evaluate serum Lipocalin-2 levels in inflammatory acne vulgaris patients and to reveal the possible relation between its serum levels and the insulin resistance status in acne patients. Patients and Methods The study included 60 patients suffering from inflammatory acne vulgaris and 60 healthy control subjects. Full general and dermatological examination were performed, recording of BMI, GAGS score was done. Then, measurement of fasting insulin and fasting glucose was performed to calculate HOMA-IR. Results Serum lipocalin-2, fasting insulin and HOMA-IR levels were significantly higher in acne patients compared to control subjects. Conclusion Inflammatory acne vulgaris patients have higher levels of serum lipocalin-2 which might be related to acne pathogenesis.

Higher serum lipocalin 2 is associated with post-stroke depression at discharge

Background and aimsPost-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge.MethodsA total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis.ResultsIn our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317–5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%.ConclusionsHigh serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

Association between lipocalin-2 and mild cognitive impairment or dementia: A systematic review and meta-analysis of population-based evidence.

The associations between lipocalin-2 (LCN2) with mild cognitive impairment (MCI) and dementia have gained growing interest. However, population-based studies have yielded inconsistent findings. Therefore, we conducted this essential systematic review and meta-analysis to analyze and summarize the existing population-based evidence. PubMed, EMBASE, and Web of Science were systematically searched until Mar 18, 2022. Meta-analysis was performed to generate the standard mean difference (SMD) of peripheral blood and cerebrospinal fluid (CSF) LCN2. A qualitative review was performed to summarize the evidence from postmortem brain tissue studies. In peripheral blood, the overall pooled results showed no significant difference in LCN2 across Alzheimer's disease (AD), MCI and control groups. Further subgroup analysis revealed higher serum LCN2 levels in AD compared to controls (SMD =1.28 [0.44;2.13], p=0.003), while the difference remained insignificant in plasma (SMD =0.04 [-0.82;0.90], p=0.931). Besides, peripheral blood LCN2 were higher in AD when age difference between AD and controls ≥4 years (SMD =1.21 [0.37;2.06], p=0.005). In CSF, no differences were found in LCN2 across groups of AD, MCI and controls. However, CSF LCN2 was higher in vascular dementia (VaD) compared to controls (SMD =1.02 [0.17;1.87], p=0.018), as well as compared to AD (SMD =1.19 [0.58;1.80], p<0.001). Qualitative analysis supported that LCN2 was increased in the brain tissue of AD-related areas, especially in astrocytes and microglia; while LCN2 increased in infarct-related brain areas and over-expressed in astrocytes and macrophages in mixed dementia (MD). The difference in peripheral blood LCN2 between AD and controls may be affected by the type of biofluid and age. No differences were found in CSF LCN2 across AD, MCI and controls groups. In contrast, CSF LCN2 was elevated in VaD patients. Moreover, LCN2 was increased in AD-related brain areas and cells in AD, while in infarcts-related brain areas and cells in MD.

Features of coronary pathology and its relationship with myocardial fibrosis markers in patients with resistant hypertension

Aim. To evaluate the severity of coronary atherosclerosis and its association with biochemical markers of fibrosis in patients with coronary artery disease (CAD) and resistant hypertension (RHT).Material and methods. The study included 39 patients with CAD and RHT. All patients underwent 24-hour blood pressure (BP) monitoring, office BP numbers were measured. Laboratory diagnostics included routine tests, as well as determination of serum lipocalin, plasma concentration of matrix metalloproteinases 2 and 9 (­MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinases-1 (TIMP 1). Coronary atherosclerosis in patients was assessed retrospectively according to medical records with an assessment of the protocols of invasive coronary angiography and multislice computed tomography, performed no more than a year ago from the moment of inclusion in the study with no clinical signs of CAD progression. Obstructive atherosclerosis was considered a coronary artery narrowing by more than 50%.Results. Considering the results of previous coronary angiography, the patients were divided into two groups. In the first group (n=20), coronary artery stenosis was &lt;50%, in the second (n=19) &gt;50% (p&lt;0,05). The compared groups of patients were comparable in sex, age, duration of hypertension, blood pressure level, and the number of antihypertensive drugs taken. There were no differences in blood lipid profile, basal glycemia, uric acid levels, and the frequency of previous cerebral accidents. However, the incidence of diabetes in group 2 was significantly higher (p&lt;0,05). Additionally, there was a significant difference in serum levels of lipocalin and MMP-2 with higher values of these indicators in patients with coronary atherosclerosis stenosis (p=0,02).Conclusion. In patients with RHT with symptoms and signs of myocardial ische­­mia, the incidence of obstructive coronary atherosclerosis according to coronary angiography is 50%. Diabetes in this category of patients indicates a more frequent obstruction of coronary bed. An increase in the level of MMP-2 and lipocalin in this category of patients is associated with more severe coronary damage and can be considered as an indirect indicator of obstructive coronary atherosclerosis.

Correlation of lipocalin 2 and glycolipid metabolism and body composition in a large cohort of children with osteogenesis imperfecta

PurposeLipocalin 2 (LCN2) is a newly recognized bone-derived factor that is important in regulation of energy metabolism. We investigated the correlation of serum LCN2 levels and glycolipid metabolism, and body composition in a large cohort of patients with osteogenesis imperfecta (OI).MethodsA total of 204 children with OI and 66 age- and gender-matched healthy children were included. Circulating levels of LCN2 and osteocalcin were measured by enzyme-linked immunosorbent assay. Serum levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C) were measured by automated chemical analyzers. The body composition was measured by dual-energy X-ray absorptiometry. Grip strength and timed-up-and-go (TUG) were tested to evaluate the muscle function.ResultsSerum LCN2 levels were 37.65 ± 23.48 ng/ml in OI children, which was significantly lower than those in healthy control (69.18 ± 35.43 ng/ml, P < 0.001). Body mass index (BMI) and serum FBG level were significantly higher and HDL-C levels were lower in OI children than healthy control (all P < 0.01). Grip strength was significantly lower (P < 0.05), and the TUG was significantly longer in OI patients than healthy control (P < 0.05). Serum LCN2 level was negatively correlated to BMI, FBG, HOMA-IR, HOMA-β, total body, and trunk fat mass percentage, and positively correlated to total body and appendicular lean mass percentage (all P < 0.05).ConclusionsInsulin resistance, hyperglycemia, obesity, and muscle dysfunction are common in OI patients. As a novel osteogenic cytokine, LCN2 deficiency may be relevant to disorders of glucose and lipid metabolism, and dysfunction of muscle in OI patients.

Assessment of Serum Lipocalin-2 Level as Early Predictor Marker to Severe COVID-19 Disease

Assessment of Serum Lipocalin-2 Level as Early Predictor Marker to Severe COVID-19 Disease

Serum Osteocalcin, Sclerostin and Lipocalin-2 Levels in Adolescent Boys with Obesity over a 12-Week Sprint Interval Training.

The aim of the study was to examine the effects of supervised cycling sprint interval training (SIT) on serum osteocalcin, lipocalin-2 and sclerostin levels, and bone mineral characteristics among obese adolescent boys. Untrained obese adolescent boys aged 13.4 ± 0.3 were assigned to either a 12-week SIT group (3 sessions/week), or a non-exercising control group who continued with their habitual everyday life. Serum osteocalcin, lipocalin-2 and sclerostin concentrations, and bone mineral values were assessed before and after intervention. After 12-week intervention, where 14 boys in both groups ended the study, there were no significant differences in serum osteokine levels between the groups after 12 weeks, while whole body bone mineral content and lower limb bone mineral density increased in the SIT group (p < 0.05). Change in body mass index was negatively correlated with the change in osteocalcin (r = -0.57; p = 0.034), and positively correlated with the change in lipocalin-2 levels (r = 0.57; p = 0.035) in the SIT group. Supervised 12-week SIT intervention improved bone mineral characteristics, but did not change osteocalcin, lipocalin-2 or sclerostin levels in adolescent boys with obesity.

Circulating lipocalin-2 as a novel biomarker for early neurological deterioration and unfavorable prognosis after acute ischemic stroke.

Lipocalin-2 (LCN2) is an acute-phase protein that could mediate neuroinflammation after brain injury. We aimed to evaluate if LCN2 level was associated with early neurological deterioration (END) in acute ischemic stroke patients, thus hindering clinical recovery. We conducted a prospective study of acute ischemic stroke patients between June 2021 and February 2022. Serum LCN2 concentration was measured after admission using an enzyme-linked immunosorbent assay. Outcomes included END and 90-day poor functional outcome (modified Rankin Scale 3-6). The National Institutes of Health Stroke Scale increment ≥4 points within 72h after admission was defined as END. A total of 253 acute ischemic stroke patients (mean age, 65.2±13.4 years; 64.0% male) were recruited. In the multivariate adjustment, increased serum LCN2 levels (per 1-SD increase of LCN2) were associated with a higher risk of END (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.20-2.25; p=.002) and 90-day poor outcome (OR, 1.73; 95% CI, 1.22-2.45; p=.002). Restricted cubic splines found a linear relationship between LCN2 level and 90-day unfavorable outcome (END, p=.001 for linearity; 90-day poor outcome, p=.013 for linearity). Subgroup analysis further confirmed the significant association of LCN2 with clinical outcomes. This study demonstrated that higher circulating LCN2 level was associated with an increased risk of early clinical worsening and 90-day unfavorable outcomes in ischemic stroke patients.

LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia

BackgroundCancer cachexia is a deadly wasting syndrome that accompanies various diseases (including ~ 50% of cancers). Clinical studies have established that cachexia is not a nutritional deficiency and is linked to expression of certain proteins (e.g., interleukin-6 and C-reactive protein), but much remains unknown about this often fatal syndrome.MethodsFirst, cachexia was created in experimental mouse models of lung cancer. Samples of human lung cancer were used to identify the association between the serum lipocalin 2 (LCN2) level and cachexia progression. Then, mouse models with LCN2 blockade or LCN2 overexpression were used to ascertain the role of LCN2 upon ferroptosis and cachexia. Furthermore, antibody depletion of tissue-infiltrating neutrophils (TI-Neu), as well as myeloid-specific-knockout of Lcn2, were undertaken to reveal if LCN2 secreted by TI-Neu caused cachexia. Finally, chemical inhibition of ferroptosis was conducted to illustrate the effect of ferroptosis upon tissue wasting.ResultsProtein expression of LCN2 was higher in the wasting adipose tissue and muscle tissues of experimental mouse models of lung cancer cachexia. Moreover, evaluation of lung cancer patients revealed an association between the serum LCN2 level and cachexia progression. Inhibition of LCN2 expression reduced cachexia symptoms significantly and inhibited tissue wasting in vivo. Strikingly, we discovered a significant increase in the number of TI-Neu in wasting tissues, and that these innate immune cells secreted high levels of LCN2. Antibody depletion of TI-Neu, as well as myeloid-specific-knockout of Lcn2, prevented ferroptosis and tissue wasting in experimental models of lung cancer cachexia. Chemical inhibition of ferroptosis alleviated tissue wasting significantly and also prolonged the survival of cachectic mice.ConclusionsOur study provides new insights into how LCN2-induced ferroptosis functionally impacts tissue wasting. We identified LCN2 as a potential target in the treatment of cancer cachexia.

Increased visinin-like protein-1, YKL-40, lipocalin-2, and IL-23 levels in patients with migraine

ABSTRACT Background Migraine is a type of primary headache caused by changes in the trigeminal system and has been reported to be associated with neurovascular inflammation of cerebral and extracerebral vessels. Objective It is known that inflammation is an important process in the pathogenesis of migraine. It has been shown that the molecules of visinin-like protein 1 (Vilip-1), YKL-40, lipocalin-2 and interleukin (IL)-23 play a role in the inflammatory process. Our aim is to investigate the role of this molecule in the metabolic pathway of migraine disease. Methods Fifty migraine patients with and without aura in the interictal period were included in the study. Vilip-1, YKL-40, lipocalin-2, and IL-23 levels were measured by ELISA method. Results Serum vilip-1, YKL-40, lipocalin-2, and IL-23 levels were found to be significantly higher in migraine patients compared to the control group. We found that this molecule increased significantly in migraine subgroups compared to the control group (p < 0.001). A positive significant correlation was found between vilip-1 level and YKL-40 and lipocalin-2 levels in migraine patients. In addition, a positive correlation was observed between visual analogue scale score, number of days with pain and vilip-1 level (p < 0.01). The results of our study showed that activation of inflammatory mediators may play a role in the pathogenesis of migraine disease. In addition, our study is valuable in that inflammatory molecules are high in the interictal period and these biomarkers have never been analyzed in migraine patients. However, we still believe that larger studies are needed to explain the role of vilip-1, YKL-40, lipocalin-2, and IL-23 in the molecular mechanism of migraine disease.