Glycoprotein Alpha Research Articles

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

BackgroundThis multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD).MethodsPatients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC.ResultsA total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426).ConclusionsSerum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Expression of Zinc Alpha-2 Glycoprotein in Oral Squamous Cell Carcinoma and Oral Dysplasia

Expression of Zinc Alpha-2 Glycoprotein in Oral Squamous Cell Carcinoma and Oral Dysplasia

Evaluation of Serum Leucine-Rich Alpha-2 Glycoprotein as a New Inflammatory Biomarker of Inflammatory Bowel Disease.

Studies on serum leucine-rich alpha-2 glycoprotein (LRG) in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are scarce; the methods for estimating disease activity are less established, particularly for CD. This study is aimed at evaluating the utility of serum LRG as a potential inflammatory marker for IBD and to investigate the LRG gene expression in peripheral blood mononuclear cells (PBMCs) as a possible source of serum LRG. Overall, 98 patients with UC and 96 patients with CD were prospectively enrolled and clinically evaluated; 92 age-matched individuals served as the healthy controls. The blood samples were analyzed for serum LRG levels and routine laboratory parameters. Disease activity was assessed clinically and endoscopically. Finally, LRG gene expression in the PBMCs from a different cohort (41 patients with UC, 34 patients with CD, and 30 healthy controls) was examined. The serum LRG levels were higher during active disease than during inactive disease; additionally, serum LRG levels were positively correlated with clinical disease activity, C-reactive protein (CRP) levels, and other laboratory parameters in patients with UC and CD and with endoscopic disease activity in UC. UC and CD showed comparable areas under the curve (AUC) values for determining clinical remission and differentiating between endoscopic remission associated with LRG and CRP. The levels of LRG mRNA were also increased in PBMCs from patients with UC and CD and reflected disease activity. These data suggest that serum LRG, originated partially from PBMCs, is an inflammatory marker in UC and CD. A large-scale well-designed study should be conducted in the future to more accurately reveal the clinical significance of LRG in patients with IBD.

Pancreatic Cancer Risk Prediction Model Using a Multi-biomarker Panel

The pancreatic ductal adenocarcinoma (PDAC) has dismal survival rate due to late detection. Thus, many researches have been tried to discover diagnostic biomarkers for early detection of PDAC. Previously, we developed the triple marker panel, including leucine-rich alpha-2 glycoprotein (LRG1), transthyretic (TTR), and CA 19-9, with sensitivity of 82.5%; specificity of 92.1% 1. Now, in this study, using this panel, we were to discover a risk prediction model for pancreatic cancer for early diagnosis with the enzyme-linked immunosorbent assay (ELISA). There were 744 samples assessed with ELISA, including PDACs (n=396) and normal samples (n=348). We proposed a risk prediction model with machine-learning method, logistic regression (LR), and compared it with support vector machine (SVM) and random forest (RF). To commercialize this model, we searched two optimal thresholds to distinguish three risk groups (high, intermediate, and low) that reliably satisfy four measurements, negative predictive value (NPV), positive predictive value (PPV), sensitivity (SEN), and specificity (SPE), simultaneously greater than 0.95%. The Pearson correlation between the triple marker panel examined with ELISA and the individual marker panel examined with ELISA 1 was 0.884. The risk prediction model distinguished pancreatic cancer from normal individuals with AUC 0.935. The thresholds in between low, intermediate and high groups were 0.11 and 0.77, that satisfied NPV 95.15%, PPV 97.55%, SEN 97.55%, and SPE 95.15%.We first validated reproducibility of the performance of the triple marker panel in this study. And our risk prediction model for pancreatic cancer achieved high accuracy prediction, which can be easily used in the clinic.

Evaluation of leucine-rich alpha-2 glycoprotein as a biomarker of fetal infection.

This study aimed to determine the association between umbilical cord leucine-rich alpha-2 glycoprotein (LRG) and fetal infection and investigate the underlying mechanism of LRG elevation in fetuses. We retrospectively reviewed the medical records of patients who delivered at Osaka University Hospital between 2012 and 2017 and selected those with histologically confirmed chorioamnionitis (CAM), which is a common pregnancy complication that may cause neonatal infection. The participants were divided into two groups: CAM with fetal infection (CAM-f[+] group, n = 14) and CAM without fetal infection (CAM-f[−] group, n = 31). Fetal infection was defined by the histological evidence of funisitis. We also selected 50 cases without clinical signs of CAM to serve as the control. LRG concentrations in sera obtained from the umbilical cord were unaffected by gestational age at delivery, neonatal birth weight, nor the presence of noninfectious obstetric complications (all, p > 0.05). Meanwhile, the LRG levels (median, Interquartile range [IQR]) were significantly higher in the CAM-f(+) group (10.37 [5.21–13.7] μg/ml) than in the CAM-f(−) (3.61 [2.71–4.65] μg/ml) or control group (3.39 [2.81–3.93] μg/ml; p < 0.01). The area under the receiver operating characteristic (ROC) curve of LRG for recognizing fetal infection was 0.92 (optimal cutoff, 5.08 μg/ml; sensitivity, 86%; specificity, 88%). In a mouse CAM model established by lipopolysaccharide administration, the fetal LRG protein in sera and LRG mRNA in the liver were significantly higher than those in phosphate-buffered saline (PBS)-administered control mice (p < 0.01). In vitro experiments using a fetal liver-derived cell line (WRL68) showed that the expression of LRG mRNA was significantly increased after interleukin (IL)-6, IL-1β, and tumor necrosis factor- alpha (TNF-α) stimulation (p < 0.01); the induction was considerably stronger following IL-6 and TNF-α stimulation (p < 0.01). In conclusion, LRG is an effective biomarker of fetal infection, and fetal hepatocytes stimulated with inflammatory cytokines may be the primary source of LRG production in utero.

Leucine-rich alpha-2 glycoprotein (LRG): A novel acute phase protein expressed in Stage 3 Grade C periodontitis before and after periodontal therapy.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel acute phase protein involved in inflammation-associated diseases and that considered to be induced by multiple proinflammatory cytokines. This study aimed to investigate gingival crevicular fluid (GCF) and serum levels of LRG, interleukin (IL)-6 and tumor necrosis factor (TNF)-α in patients with Stage 3 periodontitis before and after non-surgical periodontal treatment. Twenty-five Stage 3 periodontitis and twenty-five periodontally healthy individuals were enrolled in the study. Clinical periodontal measurements were recorded; periodontitis patients received non-surgical periodontal treatment, and GCF and serum samples were obtained at baseline and at 6weeks after treatment. LRG, IL-6 and TNF-α were determined by ELISA. GCF and serum LRG, IL-6 and TNF-α were significantly higher in periodontitis group than healthy controls (P<.001). A significant decrease in GCF and serum LRG, IL-6 and TNF-α was detected after periodontal treatment compared with baseline values of periodontitis patients (P<.001). Our findings revealed that LRG expression was increased in Stage 3 periodontitis both locally and systemically, and non-surgical periodontal therapy was effective in reducing LRG levels in GCF and serum of these patients.

Childhood anemia and iron deficiency in sub-Saharan Africa – risk factors and prevention: A review

Iron deficiency and iron deficiency anemia are public health issues recognised by the World Health Organisation, especially in sub-Saharan Africa. In some countries on this continent, the prevalence of anemia exceeds 60% in the pediatric population. Iron supplementation could prevent around one third of anemia cases in children in Africa and could decrease morbidity and mortality. A number of factors are behind this anemia, including iron deficiency caused by an inadequate diet, pica and geophagia, as well as chronic inflammation (malaria, digestive and urinary parasites, etc.). Ferritin is a good indicator of the body's iron stores, but it is not a specific reflection, with both inflammation and infection causing an increase. Ferritin could be interpreted according to C-reactive protein (CRP) or alpha-1 glycoprotein (AGP), or by adjusting the ferritin threshold to 30μg/L. The treatment of malaria and digestive or urinary worms, the correction of factors that stimulate inflammation, the fight against geophagia, as well as more hygienic living conditions, are all prerequisites for overcoming iron deficiency. A number of campaigns using iron supplements have proven to be effective, especially in schools, to fight against iron deficiency and malnutrition. Biofortification is an innovative and promising cultivation technique that increases the content of bioavailable iron in local produce such as beans. It will become a lever in the fight against iron deficiency.

LABEL-FREE QUANTITATIVE PROTEOMICS REVEALS TIME-SERIES PROTEIN SIGNATURE OF FIRST 24 HOURS AFTER CLINICAL HEART TRANSPLANTATION

Purpose: Cardiac allografts are subjected to ischemic preservation before transplantation, and subsequent ischemia-reperfusion injury (IRI) after the surgery. IRI increases the risk for acute rejection development, and more detailed detection methods for early allograft injury and rejection are therefore warranted. Systemic molecular phenotyping by proteomics is a novel method for investigating the underlaying pathophysiology. Plasma protein expressions reflect the ongoing clinical state of the patients, therefore enabling real-time screening of biomarkers for allograft injury or treatment efficacy.Here, we systemically analyze the proteomic signature of recipients within first 24h after transplantation. Methods: This study is a post hoc analysis of data collected from 50 heart transplant recipients that participated in a separate clinical trial. Plasma samples from 1 and 24 hours after transplantation were analyzed with quantitative label-free proteomics in high definition MSE mode (HDMSE). Results: With two or more unique proteins per identification, 463 proteins were quantified. A complete separation between 1h and 24h based on a set of 270 identified proteins (p-value <0.05) was seen in supervised and unsupervised classification techniques, such as orthogonal projections on latent structure-discriminant analysis (OPLS-DA) and self-organizing maps. Identified proteins were studied further by pathway, network, and protein-protein interaction analyses. Using OPLS-DA approach, we obtained a set of 13 S-plot proteins (Hemoglobin subunit beta, Hemoglobin subunit alpha, Keratin type I cytoskeletal 9, Malate dehydrogenase, Electron transfer flavoprotein beta subunit lysine methyltransferase, Zona pellucida-binding protein 1, Carbonic anhydrase 1, 14-3-3 protein epsilon, Rootletin, C-reactive protein, Serum amyloid A-1 protein, Leucine-rich alpha-2 glycoprotein and Alpha-1-antichymotrypsin) that most significantly separated recipients at 1h from 24h. Conclusion: We show the change in proteomic signature of the first 24h after heart transplantation in human blood samples with open-label proteomics. We will further compare the proteomic data to clinical parameters in order to search for prognostic factors for rejection and mortality.

Improving the iron status of school children through a school noon meal programme with meals prepared using a multiple micronutrient-fortified salt in Tamil Nadu, India.

To improve the iron status of school children through noon meals prepared using a multiple micronutrient-fortified salt. Children from a randomly selected school who consumed (intervention) and did not consume (reference) a noon meal prepared using a multiple micronutrient- fortified salt were studied over 1 year. A pre-post-test design for children aged 5-17years in reference (n=100) and intervention (n=128) groups was used. Levels of serum ferritin, soluble transferrin receptor (sTfR), alpha glycoprotein (AGP), and C-reactive protein (CRP) were assessed at baseline and at 1 year. In a subsample, urinary iodine was assessed. sTfR decreased in the intervention group (-0.80 mg/L) but increased in the reference group (0.47 mg/L) at 1 year (p=0.0001).Body iron stores (BIS) increased in the intervention group (0.09 mg/kg body weight) and decreased (-0.58 mg/kg body weight) in the reference group at 1 year (p=0.028).These findings indicate an increase in iron deficiency in the reference group and a decrease in the intervention group. However, no changes in serum ferritin and urinary iodine were observed in either group or between groups. Iron status can be improved in schoolchildren in Tamil Nadu by increasing the amount of micronutrients in the fortified salt used for preparing noon-time school meals.

Zinc α-2 Glycoprotein (ZAG) a Novel Biomarker for the Detection of Oral Squamous Cell Carcinoma

Oral cancer, the most challenging and life threatening disease in the field of dentistry, may start as a reactive lesion due to constant stimulus from tobacco consumption, transform into a pre-malignant lesion (dysplastic lesion) and ultimately develop into a cancerous lesion (Invasive carcinoma). There is a fundamental revolution taking place in the analyzing methods; extraction of biological protein from the saliva rather than from tissues or blood. Several of the biomarkers have been studied with pro-carcinogenic effects like Interleukins (ILs), tumor necrosis factor (TNF) and leptin, but only a few have been stated in the literature, which show anti-cancer characteristics like adiponectin and zinc alpha-2 glycoprotein. This review explored the diagnostic and prognostic values of a biomarkers zinc alpha-2 glycoprotein (ZAG) in adults suspected of oral squamous cell carcinoma (OSCC). The PubMed, EMBASE and Google Scholar were searched for scientific studies reported on the potential mechanism of zinc alpha-2 glycoprotein. All the research articles were selected in which ZAG is applied solely or in conjunction with other biomarkers in oral cancer and other cancers. These literatures were carefully assessed to find out and compile the diagnostic and prognostic values and to inquire therapeutic action of ZAG in the process of carcinogenesis.

Leucine-rich alpha-2 glycoprotein 1, high mobility group box 1, matrix metalloproteinase 3 and annexin A1 as biomarkers of ulcerative colitis endoscopic and histological activity.

The LRG, HMGB1, MMP3 and ANXA1 proteins have been implicated in different inflammatory pathways in ulcerative colitis (UC), but their role as specific biomarkers of both endoscopic and histological activity has yet to be elucidated. In the present study, we aimed to evaluate the LRG1, HMGB1, MMP3 and ANXA1 as potential serum biomarkers for UC endoscopic and histological activity. This cross-sectional study included UC patients under 5-ASA, and healthy controls (HC) undergoing colonoscopy. Blood and biopsy samples were obtained and endoscopic Mayo sub-score (Ms) was recorded for the UC patients. Intramucosal calprotectin as a marker of histologic activity was evaluated in all biopsy samples and serum LRG1, HMGB1, MMP3 and ANXA1 levels were measured in the blood samples. The HCs ANXA1 level was lower compared to that of the UC group [P = 0.00, area under the curve (AUC) = 0.881] and so was the HCs MMP3 level compared to that of patients (P = 0.00, AUC = 0.835). The HCs ANXA1 levels were also lower compared to these of the independent Ms groups, even to the Ms = 0 (P = 0.00, AUC = 0.913). UC endoscopic activity was associated with MMP3 levels (r = 0.54, P = 0.000) but not with ANXA1, LRG1 and HMGB1 levels CONCLUSION: Serum ANXA1 is a potential diagnostic biomarker of UC and serum MMP3 is a potential biomarker of UC endoscopic and histological activity.

Targeted mutation of secretogranin-2 disrupts sexual behavior and reproduction in zebrafish

The luteinizing hormone surge is essential for fertility as it triggers ovulation in females and sperm release in males. We previously reported that secretoneurin-a, a neuropeptide derived from the processing of secretogranin-2a (Scg2a), stimulates luteinizing hormone release, suggesting a role in reproduction. Here we provide evidence that mutation of the scg2a and scg2b genes using TALENs in zebrafish reduces sexual behavior, ovulation, oviposition, and fertility. Large-scale spawning within-line crossings (n = 82 to 101) were conducted. Wild-type (WT) males paired with WT females successfully spawned in 62% of the breeding trials. Spawning success was reduced to 37% (P = 0.006), 44% (P = 0.0169), and 6% (P < 0.0001) for scg2a-/- , scg2b-/- , and scg2a-/-;scg2b-/- mutants, respectively. Comprehensive video analysis indicates that scg2a-/-;scg2b-/- mutation reduces all male courtship behaviors. Spawning success was 47% in saline-injected WT controls compared to 11% in saline-injected scg2a-/-;scg2b-/- double mutants. For these mutants, spawning success increased 3-fold following a single intraperitoneal (i.p.) injection of synthetic secretoneurin-a (P = 0.0403) and increased 3.5-fold with injection of human chorionic gonadotropin (hCG). Embryonic survival at 24 h remained on average lower in scg2a-/-;scg2b-/- fish compared to WT injected with secretoneurin-a (P < 0.001). Significant reductions in the expression of gonadotropin-releasing hormone 3 in the hypothalamus, and luteinizing hormone beta and glycoprotein alpha subunits in the pituitary provide evidence for disrupted hypothalamo-pituitary function in scg2a and scg2b mutant fish. Our results indicate that secretogranin-2 is required for optimal reproductive function and support the hypothesis that secretoneurin is a reproductive hormone.

MON-480 Isolated Hyperthyroxinemia - Does Everyone Needs Treatment?

Background: Raised free thyroxine (T4) with normal thyroid stimulating hormone (TSH) levels should be identified and interpreted with caution. Some of these conditions do not need treatment. We present three cases with similar biochemical abnormalities from three different causes. Case 1: A 62-year-old clinically asymptomatic lady was referred to us with Free T4 34.9 pmol/L (10.0 – 24.0 pmol/L), TSH 0.81 mU/L (0.2 – 5.0 mu/L) and negative TSH receptor antibodies (<0.9 IU/L). She was trialled on antithyroid drugs for 6 months. Her Free T4 stayed elevated between 29.0 – 35.0 pmol/L with normal TSH. We worked up for assay interference by running tests on two analysers, Roche Cobas e801 and Siemens ADIVA Centaur CP, both yielded similar results. Alpha1 glycoprotein subunits and SHBG were normal with clinical euthyroid status making TSHoma less likely. Serum protein electrophoresis did not detect any abnormal albumin. We were unable to perform equilibrium dialysis due to non-availability of facility at our centre. Due to strong clinical suspicion and family history of thyroid dysfunction that never needed a treatment, we tested her genetically for familial dysalbumineic hyperthyroxinemia (FDH) using mutation surveyor and fluorescent sequence analysis showed her to be heterozygous for c.725G>A ALB variant confirming diagnosis of FDH. Case 2: A 65-year-old clinically asymptomatic lady, was referred to us with Free T4 28.8 pmol/L (10.0 – 24.0 pmol/L) and TSH 2.50 mU/L (0.2 – 5.0 mu/L). Given inappropriately normal TSH levels, we repeated her TFTs using 3 different analysers, Roche cobas e801, Siemens ADIVA centaur CP and Abbot ARCHITECT i1000SR. Roche and Siemens assays yielded similar results, however Abbot assay showed normal thyroid function tests with TSH 1.01 mu/L (0.4-5.0 mu/L) and free T4 18.7pmol/L (9.0-19.0 pmol/L), confirming assay interference. As Siemens and Roche uses streptavidin-biotin immobilizing system while Abbot uses a magnetic bead-based capture system, the abnormal results could be due to biotin interference. Case 3: A 65-year-old lady, clinically asymptomatic was referred to us with Free T4 29.2 pmol/L (10.0 – 24.0 pmol/L) and TSH 1.59 mU/L (0.2 – 5.0 mu/L), 3 months after stopping amiodarone, which she took for 3 weeks for atrial fibrillation. This was thought to be due to amiodarone, owing to its long half-life of 58 days. We repeated thyroid function tests in 3 months from first clinical encounter i.e. 6 months after stopping amiodarone that showed Free T4 24.2pmol/L and TSH 2.30 mU/L and repeated further 3 months later that were normal, confirming amiodarone induced abnormal biochemical profile requiring no treatment. Conclusion: Hyperthyroxinaemia with normal TSH need to be interpreted with caution as illustrated above. Some of them do not need treatment and inappropriate interpretation can potentially cause anxiety for the patient and harm due to unnecessary treatment.

Leucine-rich alpha 2 glycoprotein is a new marker for active disease of tuberculosis

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health problem. At present, prior exposure to Mtb can be determined by blood-based interferon-gamma release assay (IGRA), but active TB is not always detectable by blood tests such as CRP and ESR. This study was undertaken to investigate whether leucine-rich alpha-2 glycoprotein (LRG), a new inflammatory biomarker, could be used to assess active disease of TB. Cynomolgus macaques pretreated with or without Bacille Calmette-Guerin (BCG) vaccination were inoculated with Mtb to induce active TB. Blood was collected over time from these animals and levels of LRG as well as CRP and ESR were quantified. In the macaques without BCG vaccination, Mtb inoculation caused extensive TB and significantly increased plasma CRP and LRG levels, but not ESR. In the macaques with BCG vaccination, whereas Mtb challenge caused pulmonary TB, only LRG levels were significantly elevated. By immunohistochemical analysis of the lung, LRG was visualized in epithelioid cells and giant cells of the granulation tissue. In humans, serum LRG levels in TB patients were significantly higher than those in healthy controls and declined one month after anti-tubercular therapy. These findings suggest that LRG is a promising biomarker when performed following IGRA for the detection of active TB.

Gene expression of leucine-rich alpha-2 glycoprotein in the polypoid lesion of inflammatory colorectal polyps in miniature dachshunds.

Inflammatory colorectal polyps (ICRPs) in miniature dachshunds (MDs) are speculated to be a breed-specific inflammatory bowel disease (IBD). Leucine-rich alpha-2 glycoprotein (LRG) has been identified as a novel biomarker of human IBD. The aim of this study was to examine LRG gene expression in the polypoid lesions of ICRPs. Polypoid lesion specimens were collected from 24 MDs with ICRPs. Nonpolypoid colonic mucosa was collected from 18 MDs with ICRPs and 10 controls. The gene expression of LRG, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and IL-22 was examined. The expression of LRG gene was significantly increased in the polypoid lesions of ICRPs and correlated with that of the four cytokines. In conclusion, the LRG gene was expressed within the polypoid lesions of ICRPs and might be associated with local cytokine expression.

Abstract 663: Diagnostic screen for lung cancer using high throughput metabolomics screen

Abstract Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States, cigarette smoking being leading cause of lung cancer. There are two main types of lung cancer small cell and non-small cell lung cancer (NSCLC). The most common type being NSCLC which accounts for 80-85% of all reported cases. The ability to rapidly detect / diagnose lung cancer at an early stage is critical to successful treatment selection and patient survival. The use of metabolic profiling in biomedical applications metabolic profiling is being deployed as a method for finding novel, mechanistic, biomarkers of disease with obvious potential for improving diagnosis, and patient stratification. Here we present a rapid, simple and reliable high throughput targeted LC/MS single platform, for the quantification/monitoring of small molecule metabolites, lipids and peptides. The methodology employs a single set of LC/MS conditions which facilitate TCA cycle, bile acids, biogenic amine, free fatty acids, acyl carnitines, lipids and 100 protein panel without need for user intervention. Plasma from pilot cohort of lung cancer a health control samples were evaluated using this new methodology. The methodology showed excellent reproducibility and accuracy. The peptide analysis showed that 10 peptides were shown to be markers of lung cancer, these are listed in Table 1. Acylcarnitines were quantified over a range of 5 - 625ng/mL data showed that the C14:2 tetradecadienoyl carnitine and C16:1 palmitoleoyl carnitine were elevated in lung cancer samples whereas the C8:1 octenoyl carnitine level was reduced in the lung cancer samples . Although deoxycholic acid and chendeoxycholic acid appeared to be reduced in the lung cancer samples this was determined to be not statistically relevant. A total of 29 amino acids were measured during the analysis. Using t-test with p-value FDR cutoff adjusted to 0.01 the data clearly showed that sarcosine was highly over-expressed in lung cancer samples. Table 1P02749Apolipoprotein HP19652Alpha-1-acid glycoprotein 2P68871Hemoglobin subunit betaP02671Fibrogen alpha chainP02656Apolipoprotein C-IIIP02750Leucine-rich alpha 2-glycoprotein (LRG)P00738HaptoglobinP02748Complement component C9P02763Alpha-1-acid glycoprotein 1P01011Alpha-1-antichymotrypsin Note: This abstract was not presented at the meeting. Citation Format: Robert S. Plumb, Lee Gethings, Andrew Peck. Diagnostic screen for lung cancer using high throughput metabolomics screen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 663.

Quantitative profiling of tear proteome reveals down regulation of zinc alpha-2 glycoprotein in Aspergillus flavus keratitis patients

Corneal mycotic ulceration is predominantly due to Aspergillus and Fusarium solani infection in tropical countries. In this study, we examined the proteome profile of tear samples from A. flavus keratitis patients at various stages of infection. The proteome was profiled using 2D PAGE and the protein levels were quantified using 2D DIGE. Alpha-1-antitrypsin, apolipoprotein, haptoglobin, lactoferrin and albumin were up regulated while cystatin SA III precursor, lacrimal lipocalin precursor, lacritin precursor and Zinc alpha-2 glycoprotein (ZAG) were down regulated in tear fluid. In the case of ZAG all proteoforms were down regulated as the disease progressed from early to late stage of infection. Western blot analysis confirmed the results observed using DIGE. Further, there were no gender specific differences in the levels of ZAG expression in keratitis patient tear film. Published results show up regulation of ZAG in Fusarium keratitis patient tear indicating subtle changes in the early events of host response to these two fungal pathogens. We conclude that ZAG level could be used as an indicator of A. flavus or F. solani infection, even during the early stage of the disease.

Erratum: Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis.

Erratum: Leucine-rich Alpha-2 Glycoprotein is a Serum Biomarker of Mucosal Healing in Ulcerative Colitis.

Zinc alpha2 glycoprotein protects against obesity-induced hepatic steatosis.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, impaired insulin sensitivity, and chronic low-grade inflammation. Our previous studies indicated that zinc alpha2 glycoprotein (ZAG) alleviates palmitate (PA)-induced intracellular lipid accumulation in hepatocytes. This study is to further characterize the roles of ZAG on the development of hepatic steatosis, insulin resistance (IR), and inflammation. ZAG protein levels in the livers of NAFLD patients, high-fat diet (HFD)-induced or genetically (ob/ob) induced obese mice, and in PA-treated hepatocytes were determined by western blotting. C57BL/6J mice injected with an adenovirus expressing ZAG were fed HFD for indicated time to induce hepatic steatosis, IR, and inflammation, and then biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations in these mice. The molecular mechanisms underlying ZAG-regulated hepatic steatosis were further explored and verified in mice and hepatocytes. ZAG expression was decreased in NAFLD patient liver biopsy samples, obese mice livers, and PA-treated hepatocytes. Simultaneously, ZAG overexpression alleviated intracellular lipid accumulation via upregulating adiponectin and lipolytic genes (FXR, PPARα, etc.) while downregulating lipogenic genes (SREBP-1c, LXR, etc.) in obese mice as well as in cultured hepatocytes. ZAG improved insulin sensitivity and glucose tolerance via activation of IRS/AKT signaling. Moreover, ZAG significantly inhibited NF-ĸB/JNK signaling and thus resulting in suppression of obesity-associated inflammatory response in hepatocytes. Our results revealed that ZAG could protect against NAFLD by ameliorating hepatic steatosis, IR, and inflammation.

Leucine-rich alpha-2 glycoprotein in the cerebrospinal fluid is a potential inflammatory biomarker for meningitis

BackgroundLeucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for inflammatory diseases. We evaluated the levels of LRG, interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the cerebrospinal fluid (CSF) of children with meningitis. MethodsCSF samples from 10 patients with bacterial meningitis (BM) and 10 with aseptic meningitis (AM) were evaluated. Samples from 10 patients with febrile status (FS) were used as controls. LRG levels were measured using a two-site enzyme immunoassay. IL-6 and TNF-α levels were measured using a multiplex bead-based assay. CSF examination of patients with BM at the convalescent stage was also conducted. ResultsLRG and TNF-α levels in patients with BM, and IL-6 levels in patients with BM and AM showed significant increase compared with those in FS. Patients with BM at the convalescent stage showed significantly diminished LRG and IL-6 levels. LRG and IL-6 levels in CSF were indicated to be effective predictors for BM (LRG, AUC = 0.91; IL-6, AUC = 0.85). Only LRG levels showed a significant difference between patients with BM and AM (AUC = 0.78, P = 0.034). ConclusionsLRG level could be a sensitive inflammatory biomarker for inflammatory diseases of the central nervous system, comparable with IL-6 level.