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Sample records for serum biomarker profiling

  1. Serum Metabolomics Profiling to Identify Biomarkers for Unstable Angina

    OpenAIRE

    Wei Yao; Yuxia Gao; Zheng Wan

    2017-01-01

    Although statistical evidence is clear regarding the dangerousness of unstable angina (UA), a form of coronary heart disease (CHD) characterised by high mortality and morbidity globally, it is important to recognise that diagnostic precision for the condition is unfavourable. In the present research, to gain insight into candidate biomarkers, the author draws on 1H NMR-based serum metabolic profiling to analyze the unstable angina pectoris (UAP) metabolic signatures; this constitutes an effec...

  2. Serum Metabolomics Profiling to Identify Biomarkers for Unstable Angina

    Directory of Open Access Journals (Sweden)

    Wei Yao

    2017-01-01

    Full Text Available Although statistical evidence is clear regarding the dangerousness of unstable angina (UA, a form of coronary heart disease (CHD characterised by high mortality and morbidity globally, it is important to recognise that diagnostic precision for the condition is unfavourable. In the present research, to gain insight into candidate biomarkers, the author draws on 1H NMR-based serum metabolic profiling to analyze the unstable angina pectoris (UAP metabolic signatures; this constitutes an effective way to produce medical diagnosis. 101 unstable angina pectoris patients and 132 healthy controls were enrolled and 22 serum samples from each group were analyzed. Effective separation was noted regarding the UAP and control groups, and, for the former group considered in relation to their counterpart, the serum concentrations of Lac, m-I, lipid, VLDL, 3-HB, and LDL were higher whereas the concentrations of Thr, Cr, Cho, PC/GPC, Glu, Gln, Lys, HDL, Ile, Leu, and Val were lower. The conclusion drawn in view of the results is that the plasma metabolomics examined by 1H NMR displayed promise for biomarker identification for UA. In addition to this, the analysis illuminated the metabolic processes of UA.

  3. Serum Metabolomics Profiling to Identify Biomarkers for Unstable Angina.

    Science.gov (United States)

    Yao, Wei; Gao, Yuxia; Wan, Zheng

    2017-01-01

    Although statistical evidence is clear regarding the dangerousness of unstable angina (UA), a form of coronary heart disease (CHD) characterised by high mortality and morbidity globally, it is important to recognise that diagnostic precision for the condition is unfavourable. In the present research, to gain insight into candidate biomarkers, the author draws on (1)H NMR-based serum metabolic profiling to analyze the unstable angina pectoris (UAP) metabolic signatures; this constitutes an effective way to produce medical diagnosis. 101 unstable angina pectoris patients and 132 healthy controls were enrolled and 22 serum samples from each group were analyzed. Effective separation was noted regarding the UAP and control groups, and, for the former group considered in relation to their counterpart, the serum concentrations of Lac, m-I, lipid, VLDL, 3-HB, and LDL were higher whereas the concentrations of Thr, Cr, Cho, PC/GPC, Glu, Gln, Lys, HDL, Ile, Leu, and Val were lower. The conclusion drawn in view of the results is that the plasma metabolomics examined by (1)H NMR displayed promise for biomarker identification for UA. In addition to this, the analysis illuminated the metabolic processes of UA.

  4. Overlap in serum metabolic profiles between non-related diseases: Implications for LC-MS metabolomics biomarker discovery.

    Science.gov (United States)

    Lindahl, Anna; Forshed, Jenny; Nordström, Anders

    2016-09-23

    Untargeted metabolic profiling has generated large activity in the field of clinical biomarker discovery. Yet, no clinically approved metabolite biomarkers have emerged with failure in validation phases often being a reason. To investigate why, we have applied untargeted metabolic profiling in a retrospective cohort of serum samples representing non-related diseases. Age and gender matched samples from patients diagnosed with pneumonia, congestive heart failure, lymphoma and healthy controls were subject to comprehensive metabolic profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The metabolic profile of each diagnosis was compared to the healthy control group and significant metabolites were filtered out using t-test with FDR correction. Metabolites found to be significant between each disease and healthy controls were compared and analyzed for overlap. Results show that despite differences in etiology and clinical disease presentation, the fraction of metabolites with an overlap between two or more diseases was 61%. A majority of these metabolites can be associated with immune responses thus representing non-disease specific events. We show that metabolic serum profiles from patients representing non-related diseases display very similar metabolic differences when compared to healthy controls. Many of the metabolites discovered as disease specific in this study have further been associated with other diseases in the literature. Based on our findings we suggest non-related disease controls in metabolomics biomarker discovery studies to increase the chances of a successful validation and future clinical applications. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Relevance of pre-analytical blood management on the emerging cardiovascular protein biomarkers TWEAK and HMGB1 and on miRNA serum and plasma profiling.

    Science.gov (United States)

    Basso, Daniela; Padoan, Andrea; Laufer, Thomas; Aneloni, Vittorio; Moz, Stefania; Schroers, Hannah; Pelloso, Michela; Saiz, Anna; Krapp, Medea; Fogar, Paola; Cornoldi, Paola; Zambon, Carlo-Federico; Rossi, Elisa; La Malfa, Marco; Marotti, Alberto; Brefort, Thomas; Weis, Tanja M; Katus, Hugo A; Plebani, Mario

    2017-03-01

    Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers. An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0.5, 3, 6 and 9h) and centrifugation (one or two-step). Aliquots of all processed samples were immediately frozen (-80°C) before analysis. Proteins were assayed by ELISAs, miRNA expression profile by microarray and peptidome profiling by MALDI-TOF/MS. Temperature, time and centrifugation had no impact on TWEAK and HMGB1 results, which were significantly influenced by matrix type, TWEAK levels being significantly higher (F=194.7, p<0.0001), and HMGB1 levels significantly lower (F=36.32, p<0.0001) in serum than in any other plasma type. Unsuitable miRNA results were obtained using Heparin-plasma. Serum miRNA expression profiles depended mainly on temperature, while EDTA-plasma miRNA expression profiles were strongly affected by the centrifugation method used. MALDI-TOF/MS allowed the identification of seven features as indices of pre-analytical serum (m/z at 1206, 1350, 1865 and 2021) or EDTA-plasma (m/z 1897, 2740 and 2917) degradation. Serum and EDTA-plasma allow the analysis of both proteins and miRNA emerging biomarkers of heart diseases. Refrigerated storage prevents an altered miRNA expression profile also in cases of a prolonged time-interval between blood drawing and processing. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. Characterization of Serum MicroRNAs Profile of PCOS and Identification of Novel Non-Invasive Biomarkers

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    Wei Long

    2014-04-01

    Full Text Available Background: Polycystic ovary syndrome (PCOS, the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. Method and Results: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC curve (AUC is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852 that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Conclusion: Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS.

  7. Glycoblotting method allows for rapid and efficient glycome profiling of human Alzheimer's disease brain, serum and cerebrospinal fluid towards potential biomarker discovery.

    Science.gov (United States)

    Gizaw, Solomon T; Ohashi, Tetsu; Tanaka, Masakazu; Hinou, Hiroshi; Nishimura, Shin-Ichiro

    2016-08-01

    Understanding of the significance of posttranslational glycosylation in Alzheimer's disease (AD) is of growing importance for the investigation of the pathogenesis of AD as well as discovery research of the disease-specific serum biomarkers. We designed a standard protocol for the glycoblotting combined with MALDI-TOFMS to perform rapid and quantitative profiling of the glycan parts of glycoproteins (N-glycans) and glycosphingolipids (GSLs) using human AD's post-mortem samples such as brain tissues (dissected cerebral cortices such as frontal, parietal, occipital, and temporal domains), serum and cerebrospinal fluid (CSF). The structural profiles of the major N-glycans released from glycoproteins and the total expression levels of the glycans were found to be mostly similar between the brain tissues of the AD patients and those of the normal control group. In contrast, the expression levels of the serum and CSF protein N-glycans such as bisect-type and multiply branched glycoforms were increased significantly in AD patient group. In addition, the levels of some gangliosides such as GM1, GM2 and GM3 appeared to alter in the AD patient brain and serum samples when compared with the normal control groups. Alteration of the expression levels of major N- and GSL-glycans in human brain tissues, serum and CSF of AD patients can be monitored quantitatively by means of the glycoblotting-based standard protocols. The changes in the expression levels of the glycans derived from the human post-mortem samples uncovered by the standardized glycoblotting method provides potential serum biomarkers in central nervous system disorders and can contribute to the insight into the molecular mechanisms in the pathogenesis of neurodegenerative diseases and future drug discovery. Most importantly, the present preliminary trials using human post-mortem samples of AD patients suggest that large-scale serum glycomics cohort by means of various-types of human AD patients as well as the normal

  8. DI/LC-MS/MS-Based Metabolic Profiling for Identification of Early Predictive Serum Biomarkers of Metritis in Transition Dairy Cows.

    Science.gov (United States)

    Zhang, Guanshi; Deng, Qilan; Mandal, Rupasri; Wishart, David S; Ametaj, Burim N

    2017-09-27

    The objectives of this study were to evaluate alterations of metabolites in the blood of dairy cows before, during, and after diagnosis of metritis and identify predictive serum metabolite biomarkers for metritis. DI/LC-MS/MS was used to analyze serum samples collected from both healthy and metritic cows during -8, -4, disease diagnosis, +4, and +8 wks relative to parturition. Results indicated that cows with metritis experienced altered concentrations of serum amino acids, glycerophospholipids, sphingolipids, acylcarnitines, and biogenic amines during the entire experimental period. Moreover, two sets of predictive biomarker models and one set of diagnostic biomarker models for metritis were developed, and all of them showed high sensitivity and specificity (e.g., high AUC values by the ROC curve evaluation), which indicate that serum metabolites identified have pretty accurate predictive, diagnostic, and prognostic abilities for metritis in transition dairy cows.

  9. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    Thevenon J, Callier P, Poquet H, Bache I, et al. (2014) 3q27.3 microdeletional syndrome : a recognizable clinical entity associating dysmorphic...1 2 3 Figure 2. Assessment of proteins that bind to ASD1. The ASD1 peptoid was immobilized and incubated with pooled serum from ASD or TD

  10. Serum biomarker profiles of interleukin-6, tumor necrosis factor alpha, matrix-metalloproteinase-2, and vascular endothelial growth factor in endometriosis staging

    Directory of Open Access Journals (Sweden)

    Wachyu Hadisaputra

    2013-05-01

    Full Text Available Background: The focus of this study was to compare serum biomarkers: interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α, matrix-metalloproteinase-2 (MMP-2 and vascular endothelial growth factor (VEGF in endometriosis stage I-II and stage III-IV. Methods: This is a cross-sectional study. Forty endometriosis patients were diagnosed using laparoscopy procedure. Serum sample was taken before the surgery. The serum biomarkers (IL-6, TNF-α, MMP-2, and VEGF were analyzed with ELISA method at the end of research. Mean of serum biomarkers in endometrosis stage I-II and stage III-IV were compared using unpaired t-test. Variables that show significant mean difference were tested using ROC measurement and the optimal cut-off point was determined. Results: There was no significant difference in mean serum biomarkers level of IL-6, TNF-α, and MMP-2 between endometriosis stage I-II and stage III-IV (1.58 ± 0.78 vs 1.55 ± 0.98 pg/mL, 1.5 ± 0.47 vs 1.49 ± 0.29 pg/mL, and 152.04 ± 27.32 vs 140.98 ± 28.08 ng/mL, respectively. On the other hand, the comparison of VEGF level in endometriosis stage I-II and stage III-IV demonstrated significant difference (289.76 ± 188.13 vs 581.29 ± 512.85 pg/mL (p < 0.05. Mean difference of VEGF had AUC of 74.5%. Optimal cut-off point for VEGF was ≥ 314.75 pg/mL with sensitivity 78.6% and specificity 69.2%. Conclusion: This study showed that serum biomarkers of VEGF level (but not IL-6, TNF-α, and MMP-2 can be used to measure the degree of severity in endometriosis. VEGF level of 314.75 pg/mL represents the cut-off point between lower and higher stage of severity. (Med J Indones. 2013;22:76-82Keywords: Endometriosis, interleukin-6, matrix-metalloproteinase-2, TNF-α, vascular endhothelial growth factor

  11. Do serum biomarkers really measure breast cancer?

    Directory of Open Access Journals (Sweden)

    Yurkovetsky Zoya

    2009-05-01

    Full Text Available Abstract Background Because screening mammography for breast cancer is less effective for premenopausal women, we investigated the feasibility of a diagnostic blood test using serum proteins. Methods This study used a set of 98 serum proteins and chose diagnostically relevant subsets via various feature-selection techniques. Because of significant noise in the data set, we applied iterated Bayesian model averaging to account for model selection uncertainty and to improve generalization performance. We assessed generalization performance using leave-one-out cross-validation (LOOCV and receiver operating characteristic (ROC curve analysis. Results The classifiers were able to distinguish normal tissue from breast cancer with a classification performance of AUC = 0.82 ± 0.04 with the proteins MIF, MMP-9, and MPO. The classifiers distinguished normal tissue from benign lesions similarly at AUC = 0.80 ± 0.05. However, the serum proteins of benign and malignant lesions were indistinguishable (AUC = 0.55 ± 0.06. The classification tasks of normal vs. cancer and normal vs. benign selected the same top feature: MIF, which suggests that the biomarkers indicated inflammatory response rather than cancer. Conclusion Overall, the selected serum proteins showed moderate ability for detecting lesions. However, they are probably more indicative of secondary effects such as inflammation rather than specific for malignancy.

  12. New serum biomarkers for prostate cancer diagnosis

    Science.gov (United States)

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  13. Ambience-associated variation in serum biomarkers of oxidative ...

    African Journals Online (AJOL)

    An investigation was carried out in donkeys to discover serum biomarkers of oxidative stress during moderate and extremely hot conditions. Serum biomarkers included vitamin A, vitamin C, vitamin E, glutathione, catalase, superoxide dismutase, monoamine oxidase, glutathione reductase, xanthine oxidase, oxidase and ...

  14. Serum Cartilage Biomarkers and Shoulder Instability.

    Science.gov (United States)

    Owens, Brett D; Cameron, Kenneth L; Bokshan, Steven L; Clifton, Kari B; Svoboda, Steven J; Wolf, Jennifer Moriatis

    2017-01-01

    Differences in cartilage biomarkers have been noted in patients with anterior cruciate ligament tears, but little is known about any similar relationship with shoulder instability. This study evaluated the relationship between serum cartilage biomarkers and shoulder instability. The authors present a prospective cohort study of young athletes followed from 2006 to 2010. A nested case-control analysis was conducted within this cohort to evaluate the association between preinjury collagen type II cleavage (a marker for type II collagen cleavage) and procollagen II carboxy propeptide (a marker of cartilage synthesis) and the subsequent likelihood of shoulder instability during the 4-year follow-up period. Preinjury collagen type II cleavage and procollagen II carboxy propeptide levels in 51 subjects who had shoulder instability were compared with levels in 210 subjects without documented anterior cruciate ligament or shoulder instability (control group) with commercially available enzyme-linked immunosorbent assay kits. Mean preinjury collagen type II cleavage levels in patients who subsequently had shoulder instability were significantly lower than those in the control group (73.91 vs 79.24 pg/mL, P=.03). No significant difference was found in preinjury procollagen II carboxy propeptide levels compared with the control group (359.94 vs 396.37, P=.24). This study is the first to examine the relationship between baseline collagen biomarkers and subsequent shoulder instability. The finding of lower baseline collagen type II cleavage levels in patients with subsequent shoulder instability may represent a genetic predisposition or a compensatory mechanism by which cartilage degradation is decreased in those who are more likely to have instability. [Orthopedics. 2017; 40(1):34-36.]. Copyright 2016, SLACK Incorporated.

  15. A Synopsis of Serum Biomarkers in Cutaneous Melanoma Patients

    OpenAIRE

    Pierre Vereecken; Frank Cornelis; Nicolas van Baren; Valérie Vandersleyen; Jean-François Baurain

    2012-01-01

    Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found...

  16. Biomarkers of Exposure to Triclocarban in Urine and Serum

    Science.gov (United States)

    Ye, Xiaoyun; Zhou, Xiaoliu; Furr, Johnathan; Ahn, Ki Chang; Hammock, Bruce D.; Gray, Earl L.; Calafat, Antonia M.

    2012-01-01

    3, 4, 4’- Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after administering TCC once (500 mg/kg body weight) by oral gavage. Urine was collected 0–24 hours before dosing, and 0–24 hours and 24–48 hours after dosing. Serum was collected at necropsy 48 h after dosing. We identified several metabolites of TCC in urine and serum by on-line solid phase extraction-high performance liquid chromatography- mass spectrometry. We unambiguously identified two major oxidative metabolites of TCC, 3’-hydroxy-TCC and 2’-hydroxy-TCC, by comparing their chromatographic behavior and mass spectral fragmentation patterns with those of authentic standards. By contrast, compared to these oxidative metabolites, we detected very low levels of TCC in the urine or serum. Taken together these data suggest that in rats, oxidation of TCC is a major metabolic pathway. We also measured TCC and its oxidative metabolites in 50 urine and 16 serum samples collected from adults in the United States. The results suggest differences in the metabolic profile of TCC in rats and in humans; oxidation appears to be a minor metabolic pathway in humans. Total (free plus conjugated) TCC could serve as a potential biomarker for human exposure to TCC. PMID:21635932

  17. Serum MicroRNAs as Diagnostic Biomarkers for Macrosomia.

    Science.gov (United States)

    Jiang, Hua; Wen, Yang; Hu, Lingmin; Miao, Tingting; Zhang, Ming; Dong, Jing

    2015-06-01

    Macrosomia is defined as an infant's birth weight of more than 4000 g. Although microRNAs (miRNAs) have been implicated in the pathogenesis of various diseases, the associations between serum miRNAs and macrosomia have been rarely reported. We used the Taqman Low Density Array followed by quantitative reverse transcriptase polymerase chain reaction assays to screen for miRNAs associated with macrosomia using serum samples collected 1 week before delivery. Profiling results showed that 1 miRNA was significantly upregulated and 10 miRNAs were significantly downregulated in serum samples of macrosomia (ΔΔCt > 3-fold). The expression levels of miR-21 were significantly decreased in macrosomia as compared to the controls in the third trimester. Receiver operating characteristic (ROC) curve analyses showed that the area under the ROC curve for miR-21 was 67.7% (sensitivity = 66.7% and specificity = 70.0%). miR-21 in maternal serum is differentially expressed between macrosomia and controls, and miR-21 could be used as a candidate biomarker to predict macrosomia. © The Author(s) 2014.

  18. Identification of serum protein biomarkers for utrophin based DMD therapy.

    Science.gov (United States)

    Guiraud, Simon; Edwards, Benjamin; Squire, Sarah E; Babbs, Arran; Shah, Nandini; Berg, Adam; Chen, Huijia; Davies, Kay E

    2017-03-02

    Despite promising therapeutic avenues, there is currently no effective treatment for Duchenne muscular dystrophy (DMD), a lethal monogenic disorder caused by the loss of the large cytoskeletal protein, dystrophin. A highly promising approach to therapy, applicable to all DMD patients irrespective to their genetic defect, is to modulate utrophin, a functional paralogue of dystrophin, able to compensate for the primary defects of DMD restoring sarcolemmal stability. One of the major difficulties in assessing the effectiveness of therapeutic strategies is to define appropriate outcome measures. In the present study, we utilised an aptamer based proteomics approach to profile 1,310 proteins in plasma of wild-type, mdx and Fiona (mdx overexpressing utrophin) mice. Comparison of the C57 and mdx sera revealed 83 proteins with statistically significant >2 fold changes in dystrophic serum abundance. A large majority of previously described biomarkers (ANP32B, THBS4, CAMK2A/B/D, CYCS, CAPNI) were normalised towards wild-type levels in Fiona animals. This work also identified potential mdx markers specific to increased utrophin (DUS3, TPI1) and highlights novel mdx biomarkers (GITR, MYBPC1, HSP60, SIRT2, SMAD3, CNTN1). We define a panel of putative protein mdx biomarkers to evaluate utrophin based strategies which may help to accelerate their translation to the clinic.

  19. A New Serum Biomarker for Lung Cancer - Transthyretin

    OpenAIRE

    Liu, Liyun; Sun, Suozhu; Liu, JiFu; WU, SHANSHAN; Songwei DAI; Wang, Xiaomin; Huang, Lingyun; Xueyuan XIAO; He, Dacheng

    2009-01-01

    Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI) technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers we...

  20. Serum proteomic profiling of major depressive disorder

    Science.gov (United States)

    Bot, M; Chan, M K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B W J H

    2015-01-01

    Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models. Pooled analyses of two independent validation cohorts (totaling 78 MDD cases and 156 controls) was carried out to validate our top markers. Twenty-eight analytes differed significantly between cMDD cases and controls (P<0.05), whereas 10 partly overlapping markers differed significantly between rMDD cases and controls. Antidepressant medication use and comorbid anxiety status did not substantially impact on these findings. Sixteen of the cMDD-related markers had been assayed in the pooled validation cohorts, of which seven were associated with MDD. The analytes prominently associated with cMDD related to diverse cell communication and signal transduction processes (pancreatic polypeptide, macrophage migration inhibitory factor, ENRAGE, interleukin-1 receptor antagonist and tenascin-C), immune response (growth-regulated alpha protein) and protein metabolism (von Willebrand factor). Several proteins were implicated in depression. Changes were more prominent in cMDD, suggesting that molecular alterations in serum are associated with acute depression symptomatology. These findings may help to establish serum-based biomarkers of depression and could improve our understanding of its pathophysiology. PMID:26171980

  1. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

    NARCIS (Netherlands)

    Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A|info:eu-repo/dai/nl/413993809; Dalmeijer, Gerdien W|info:eu-repo/dai/nl/343075881; Evelein, Annemieke M V; Fauser, Bart C J M|info:eu-repo/dai/nl/071281932; de Jager, Wilco|info:eu-repo/dai/nl/304816906

    2016-01-01

    OBJECTIVE: To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. DESIGN: Cross-sectional comparison of serum biomarkers. SETTING: University Medical Center Utrecht. PATIENTS: Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n

  2. [A new serum biomarker for lung cancer - transthyretin.].

    Science.gov (United States)

    Liu, Liyun; Sun, Suozhu; Liu, Jifu; Wu, Shanshan; Dai, Songwei; Wang, Xiaomin; Huang, Lingyun; Xiao, Xueyuan; He, Dacheng

    2009-04-20

    Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI) technique. Serum sample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantly decreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR), cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

  3. Current clinical application of serum biomarkers to detect ovarian cancer.

    Science.gov (United States)

    Nowak, Marek; Janas, Łukasz; Stachowiak, Grzegorz; Stetkiewicz, Tomasz; Wilczyński, Jacek R

    2015-12-01

    For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression.

  4. A New Serum Biomarker for Lung Cancer - Transthyretin

    Directory of Open Access Journals (Sweden)

    Liyun LIU

    2009-04-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer death worldwide and very few specific biomarkers could be used in clinical diagnosis at present. The aim of this study is to find novel potential serum biomarkers for lung cancer using Surface Enhanced Laser Desorption/Ionization (SELDI technique. Methods Serumsample of 227 cases including 146 lung cancer, 13 pneumonia, 28 tuberculous pleurisy and 40 normal individuals were analyzed by CM10 chips. The candidate biomarkers were identified by ESI/MS-MS and database searching, and further confirmed by immunoprecipitation. The same sets of serum sample from all groups were re-measured by ELISA assay. Results Three protein peaks with the molecular weight 13.78 kDa, 13.90 kDa and 14.07 kDa were found significantlydecreased in lung cancer serum compared to the other groups and were all automatically selected as specific biomarkers by Biomarker Wizard software. The candidate biomarkers obtained from 1-D SDS gel bands by matching the molecular weight with peaks on CM10 chips were identified by Mass spectrometry as the native transthyretin (nativeTTR, cysTTR and glutTTR, and the identity was further validated by immunoprecipitation using commercial TTR antibodies. Downregulated of TTR was found in both ELISA and SELDI analysis. Conclusion TTRs acted as the potentially useful biomarkers for lung cancer by SELDI technique.

  5. The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Maretty-Kongstad, Katja; Keller, Johnny

    2016-01-01

    cases. Adjusting for confounders such as comorbidity and age is an essential safeguard against erroneous conclusions regarding the possible prognostic value of these biomarkers. The aim of this study was to assess the prognostic value of a battery of pretreatment biomarkers in the serum of patients......, lymphocytes, and sodium were collected from the patient records. The prognostic values of overall and disease-specific mortality were tested for each individual biomarker as well as for the Glasgow prognostic score (GPS) and for a new composite score incorporating five biomarkers (Aarhus composite biomarker...... for comorbidity and other confounders, it was found that elevated levels of CRP, low hemoglobin, low sodium, high GPS, and high ACBS were associated with increased overall mortality. Furthermore, elevated levels of CRP, low hemoglobin, high GPS, and high ACBS were associated with increased disease...

  6. Serum Protein Profile Alterations in Hemodialysis Patients

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G A; Davies, R W; Choi, M W; Perkins, J; Turteltaub, K W; McCutchen-Maloney, S L; Langlois, R G; Curzi, M P; Trebes, J E; Fitch, J P; Dalmasso, E A; Colston, B W; Ying, Y; Chromy, B A

    2003-11-18

    Background: Serum protein profiling patterns can reflect the pathological state of a patient and therefore may be useful for clinical diagnostics. Here, we present results from a pilot study of proteomic expression patterns in hemodialysis patients designed to evaluate the range of serum proteomic alterations in this population. Methods: Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (SELDI-TOFMS) was used to analyze serum obtained from patients on periodic hemodialysis treatment and healthy controls. Serum samples from patients and controls were first fractionated into six eluants on a strong anion exchange column, followed by application to four array chemistries representing cation exchange, anion exchange, metal affinity and hydrophobic surfaces. A total of 144 SELDI-TOF-MS spectra were obtained from each serum sample. Results: The overall profiles of the patient and control samples were consistent and reproducible. However, 30 well-defined protein differences were observed; 15 proteins were elevated and 15 were decreased in patients compared to controls. Serum from one patient exhibited novel protein peaks suggesting possible additional changes due to a secondary disease process. Conclusion: SELDI-TOF-MS demonstrated dramatic serum protein profile differences between patients and controls. Similarity in protein profiles among dialysis patients suggests that patient physiological responses to end-stage renal disease and/or dialysis therapy have a major effect on serum protein profiles.

  7. Haematological and serum enzymes biomarkers of heavy metals in ...

    African Journals Online (AJOL)

    Conversely, accumulation resulted in reducing Haemoglobin and an increased Red Blood Cells and Lymphocyte counts. Haematological and serum enzymes activities are predilective biomarkers for the detection and monitoring of aquatic ecosystems pollution. The inclusion of Allium sativum at 1.5g/kg is therefore ...

  8. A Synopsis of Serum Biomarkers in Cutaneous Melanoma Patients

    Directory of Open Access Journals (Sweden)

    Pierre Vereecken

    2012-01-01

    Full Text Available Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found in body fluids such as the serum. Actually, with the emergence of new targeted therapies for cancer and the increasing range of therapeutic options, the challenge for the clinician is to assess the unique risk/response ratio and the prognosis for each patient. New serum biomarkers of melanoma progression and metastatic disease are still awaited in order to provide efficient rationale for followup and treatment choices. LDH as well as S100B levels have been correlated with poor prognosis in AJCC stage III/IV melanoma patients. However, the poor sensitivity and specificity of those markers and many other molecules are serious limitations for their routine use in both early (AJCC stage I and II and advanced stages of melanoma (AJCC stage III and IV. Microarray technology and proteomic research will surely provide new candidates in the near future allowing more accurate definition of the individual prognosis and prediction of the therapeutic outcome and select patients for early adjuvant strategies.

  9. A synopsis of serum biomarkers in cutaneous melanoma patients.

    Science.gov (United States)

    Vereecken, Pierre; Cornelis, Frank; Van Baren, Nicolas; Vandersleyen, Valérie; Baurain, Jean-François

    2012-01-01

    Many serum biomarkers have been evaluated in melanoma but their clinical significance remains a matter of debate. In this paper, a review of the serum biomarkers for melanoma will be detailed and will be discussed from the point of view of their practical usefulness. The expression of biomarkers can be detected intracellularly or on the cell membrane of melanoma cells or noncancer cells in association with the melanoma. Some of these molecules can then be released extracellularly and be found in body fluids such as the serum. Actually, with the emergence of new targeted therapies for cancer and the increasing range of therapeutic options, the challenge for the clinician is to assess the unique risk/response ratio and the prognosis for each patient. New serum biomarkers of melanoma progression and metastatic disease are still awaited in order to provide efficient rationale for followup and treatment choices. LDH as well as S100B levels have been correlated with poor prognosis in AJCC stage III/IV melanoma patients. However, the poor sensitivity and specificity of those markers and many other molecules are serious limitations for their routine use in both early (AJCC stage I and II) and advanced stages of melanoma (AJCC stage III and IV). Microarray technology and proteomic research will surely provide new candidates in the near future allowing more accurate definition of the individual prognosis and prediction of the therapeutic outcome and select patients for early adjuvant strategies.

  10. Serum Lipid Profiles, Homocysteine Levels And Cardiovascular ...

    African Journals Online (AJOL)

    Despite the difference in the serum lipic profiles of the pregnant and non - pregnant women. Both groups had values of serum concentration of lipids. Folate vitamin B12 and homocysteine that were well within the reference range of values provided by the American Heart Association {AHA}. Conclusion: These result indicate ...

  11. Direct Assessment of Plasma/Serum Sample Quality for Proteomics Biomarker Investigation.

    Science.gov (United States)

    Greco, Viviana; Piras, Cristian; Pieroni, Luisa; Urbani, Andrea

    2017-01-01

    Blood proteome analysis for biomarker discovery represents one of the most challenging tasks to be achieved through clinical proteomics due to the sample complexity, such as the extreme heterogeneity of proteins in very dynamic concentrations, and to the observation of proper sampling and storage conditions. Quantitative and qualitative proteomics profiling of plasma and serum could be useful both for the early detection of diseases and for the evaluation of pathological status. Two main sources of variability can affect the precision and accuracy of the quantitative experiments designed for biomarker discovery and validation. These sources are divided into two categories, pre-analytical and analytical, and are often ignored; however, they can contribute to consistent errors and misunderstanding in biomarker research. In this chapter, we review critical pre-analytical and analytical variables that can influence quantitative proteomics. According to guidelines accepted by proteomics community, we propose some recommendations and strategies for a proper proteomics analysis addressed to biomarker studies.

  12. Serum Biomarkers of (AntiOxidant Status for Epidemiological Studies

    Directory of Open Access Journals (Sweden)

    Eugène Jansen

    2015-11-01

    Full Text Available In this review, we disclose a selection of serum/plasma biomarkers of (antioxidant status related to nutrition, which can be used for measurements in large-scale epidemiological studies. From personal experience, we have come to the following proposal of a set of biomarkers for nutritional intake, (antioxidant status, and redox status. We have selected the individual antioxidant vitamins E and A, and the carotenoids which can be measured in large series by HPLC. In addition, vitamin C was selected, which can be measured by an auto-analyzer or HPLC. As a biomarker for oxidative stress, the ROM assay (reactive oxygen metabolites was selected; for the redox status, the total thiol assay; and for the total antioxidant status the BAP assay (biological antioxidant potential. All of these biomarkers can be measured in large quantities by an auto-analyzer. Critical points in biomarker validation with respect to blood sampling, storage conditions, and measurements are discussed. With the selected biomarkers, a good set is presented for use in the risk assessment between nutrition and (chronic diseases in large-scale epidemiological studies. Examples of the successful application of these biomarkers in large international studies are presented.

  13. Diagnosis of Pancreatic Cancer Using Serum Proteomic Profiling

    Directory of Open Access Journals (Sweden)

    Sudeepa Bhattacharyya

    2004-09-01

    Full Text Available In the United States, mortality rates from pancreatic cancer (PCa have not changed significantly over the past 50 years. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. The objective of this study was to use highthroughput protein profiling technology to identify biomarkers in the serum proteome for the early detection of resectable PCa. Using surface-enhanced laser desorption/ionization mass spectrometry, protein profiles were generated from sera of 49 PCa patients and 54 unaffected individuals after fractionation on an anion exchange resin. The samples were randomly divided into a training set (69 samples and test set (34 samples, and two multivariate analysis procedures, classification and regression tree and logistic regression, were used to develop classification models from these spectral data that could distinguish PCa from control serum samples. In the test set, both models correctly classified all of the PCa patient serum samples (100% sensitivity. Using the decision tree algorithm, a specificity of 93.5% was obtained, whereas the logistic regression model produced a specificity of 100%. These results suggest that high-throughput proteomics profiling has the capacity to provide new biomarkers for the early detection and diagnosis of PCa.

  14. Evaluation of a type 1 diabetes serum cohort by SELDI-TOF MS protein profiling

    DEFF Research Database (Denmark)

    Albrethsen, J.; Kaas, A.; Schonle, E.

    2009-01-01

    Proteomics analysis of serum from patients with type 1 diabetes (T1D) may lead to novel biomarkers for prediction of disease and for patient monitoring. However, the serum proteome is highly sensitive to sample processing and before proteomics biomarker research serum cohorts should preferably...... be examined for potential bias between sample groups. S ELDI-TOF MS protein profiling was used for preliminary evaluation of a biological-bank with 766 serum samples from 270 patients with T1D, collected at 18 different paediatric centers representing 15 countries in Europe and Japan over 2 years (2000...

  15. Methodology and Applications of Disease Biomarker Identification in Human Serum

    Directory of Open Access Journals (Sweden)

    Ziad J. Sahab

    2007-01-01

    Full Text Available Biomarkers are biomolecules that serve as indicators of biological and pathological processes, or physiological and pharmacological responses to a drug treatment. Because of the high abundance of albumin and heterogeneity of plasma lipoproteins and glycoproteins, biomarkers are difficult to identify in human serum. Due to the clinical significance the identification of disease biomarkers in serum holds great promise for personalized medicine, especially for disease diagnosis and prognosis. This review summarizes some common and emerging proteomics techniques utilized in the separation of serum samples and identification of disease signatures. The practical application of each protein separation or identification technique is analyzed using specific examples. Biomarkers of cancers of prostate, breast, ovary, and lung in human serum have been reviewed, as well as those of heart disease, arthritis, asthma, and cystic fibrosis. Despite the advancement of technology few biomarkers have been approved by the Food and Drug Administration for disease diagnosis and prognosis due to the complexity of structure and function of protein biomarkers and lack of high sensitivity, specificity, and reproducibility for those putative biomarkers. The combination of different types of technologies and statistical analysis may provide more effective methods to identify and validate new disease biomarkers in blood.Abbreviations: 2-DE, two-dimensional gel electrophoresis; 2DLC-MS, two-dimensional liquid chromatography mass spectrometry; CA 15.3, cancer antigen 15.3; CA 19–9, cancer antigen 19–9, a tumor-associated antigen; CA125, cancer antigen 125, a mucin-like protein; CEA, carcinoembryonic antigen; CF, Cystic Fibrosis; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay; ESI-MS/MS, electrospray ionization tandem mass spectrometry; FDA, Food and Drug Administration; IPG, immobilized pH gradient; MALDI-TOF-MS, matrix-assisted laser desorption

  16. Correlation between preoperative serum levels of five biomarkers and relationships between these biomarkers and cancer stage in epithelial overian cancer

    National Research Council Canada - National Science Library

    Hwang, Jongyun; Na, Sunghun; Lee, Hyangah; Lee, Dongheon

    2009-01-01

    To examine the correlation among the preoperative serum levels of five biomarkers presumed to be useful for early detection of epithelial ovarian cancer and evaluate the relationships between serum...

  17. Serum biomarkers predictive of depressive episodes in panic disorder.

    Science.gov (United States)

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2016-02-01

    Panic disorder with or without comorbid agoraphobia (PD/PDA) has been linked to an increased risk to develop subsequent depressive episodes, yet the underlying pathophysiology of these disorders remains poorly understood. We aimed to identify a biomarker panel predictive for the development of a depressive disorder (major depressive disorder and/or dysthymia) within a 2-year-follow-up period. Blood serum concentrations of 165 analytes were evaluated in 120 PD/PDA patients without depressive disorder baseline diagnosis (6-month-recency) in the Netherlands Study of Depression and Anxiety (NESDA). We assessed the predictive performance of serum biomarkers, clinical, and self-report variables using receiver operating characteristics curves (ROC) and the area under the ROC curve (AUC). False-discovery-rate corrected logistic regression model selection of serum analytes and covariates identified an optimal predictive panel comprised of tetranectin and creatine kinase MB along with patient gender and scores from the Inventory of Depressive Symptomatology (IDS) rating scale. Combined, an AUC of 0.87 was reached for identifying the PD/PDA patients who developed a depressive disorder within 2 years (n = 44). The addition of biomarkers represented a significant (p = 0.010) improvement over using gender and IDS alone as predictors (AUC = 0.78). For the first time, we report on a combination of biological serum markers, clinical variables and self-report inventories that can detect PD/PDA patients at increased risk of developing subsequent depressive disorders with good predictive performance in a naturalistic cohort design. After an independent validation our proposed biomarkers could prove useful in the detection of at-risk PD/PDA patients, allowing for early therapeutic interventions and improving clinical outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The Association Between Serum Biomarkers of Collagen Turnover and Subsequent Anterior Cruciate Ligament Rupture.

    Science.gov (United States)

    Svoboda, Steven J; Owens, Brett D; Harvey, Travis M; Tarwater, Patrick M; Brechue, William F; Cameron, Kenneth L

    2016-07-01

    No study has attempted to associate the levels of preinjury serum biomarkers of collagen turnover with the subsequent risk of anterior cruciate ligament (ACL) injury. Preinjury serum biomarkers of collagen turnover would be associated with the subsequent risk of ACL injury. Case-control study; Level of evidence, 3. We conducted a case-control study with 45 ACL-injured cases and 45 controls matched for sex, age, height, and weight. In addition to the matching criteria, controls had no history of major joint injury. Baseline preinjury serum samples were obtained from the Department of Defense Serum Repository for all subjects. Samples were assessed for 2 serum biomarkers of collagen synthesis (CPII and CS846) and 2 markers of collagen degradation (C1,2C and C2C) through commercially available enzyme-linked immunosorbent assay (ELISA) kits. All ELISAs were performed in triplicate. Conditional logistic regression models were used to analyze the data. Univariate results suggested that both biomarkers for collagen degradation (C1,2C and C2C) were significantly associated with the subsequent likelihood of ACL injury. Serum C2C and C1,2C concentration at baseline were associated with odds ratios (ORs) of 2.05 (95% CI, 1.30-3.23; P = .001) and 3.02 (95% CI, 1.60-5.71; P = .002), respectively. Baseline serum CPII concentrations were also associated with subsequent ACL injury. Serum CPII concentration at baseline was associated with an OR of 4.41 (95% CI, 1.87-10.38; P = .001). Baseline serum CS846 levels approached significance (OR = 0.77; 95% CI, 0.57-1.03; P = .080). Multivariable models suggested that preinjury CPII and C2C concentrations at baseline are important indicators of subsequent ACL injury risk. Preinjury differences in serum biomarker levels of collagen turnover suggest that collagen metabolism in individuals who go on to tear an ACL may be different when compared with a matched control group with no history of major joint injury. These differences may be

  19. Comparison of peripheral and central schizophrenia biomarker profiles.

    Directory of Open Access Journals (Sweden)

    Laura W Harris

    Full Text Available We have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10 from schizophrenia patients who were mainly chronically ill and drug treated. Twenty-one analytes are differentially expressed in post-mortem brain tissue. Comparison with our previous mRNA profiling studies of the same patient samples in another frontal cortical area showed that 9 of these molecules were also altered at the transcriptional level. Furthermore, 9 of the molecules were also altered in serum from living first onset schizophrenia patients compared to controls. We propose a model in which the brain and periphery are coordinated through hormones and other regulatory molecules released into the blood via the diffuse neuroendocrine system. These findings provide further evidence for the systemic nature of schizophrenia and give added validity to the concept that schizophrenia can be investigated through studies of blood-based biomarkers.

  20. Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

    Energy Technology Data Exchange (ETDEWEB)

    Moser, Virginia C., E-mail: Moser.ginger@epa.gov [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Stewart, Nicholas; Freeborn, Danielle L. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Crooks, James; MacMillan, Denise K. [Analytical Chemistry Research Core/Research Cores Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Hedge, Joan M.; Wood, Charles E. [Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); McMahen, Rebecca L. [ORISE fellow, Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Strynar, Mark J. [Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Herr, David W. [Neurotoxicology Branch/Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

    2015-01-15

    There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects), singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics

  1. Serum Lipid Profile In Xanthelasma

    Directory of Open Access Journals (Sweden)

    Gangopadadhya D N

    1998-01-01

    Full Text Available Forty Patients of Xanthelasma palpebrarum (XP and forty age & sex related controls were collected form the skin OPD of N R S Medical College Hospital and put to clinical and biochemical examinations. XP was found to be more prevalent among female (67.5% than in male (32.5%. Majority (55% of the patients belonged to 31-50 years age group in both the sexes. Family history of XP was found in significantly more number of patients (27.5% than in controls (0%. Family history of diabetes, ischemic heart disease, and hypertension was detected in 20%, 32.5% and 20% of patients respectively and no significant difference was seen from the control. Arcus senilis was detected in25% patients. Forty percent patients were hypercholesterolaemic among which 27.5%. Patients had cholesterol level> 240mg/df whereas 5% controls had the level between 200-240mg/df. Hypertiglyceridaemia was present in 22.5% patients and 5% controls. LDL cholesterol elevation was found in more than30% cases and only slightly elevated in 5% controls. HDL Cholesterol level was below normal in 15% patients and none among control. Overall, 52.5% patients had some form of abnormal lipid profile and only 10% control had the same problem. This difference was statistically highly significant (p<0.001. Electrocardiography was abnormal in 22.5% patients and 5% controls and the difference was significant (p<0.02. Blood sugar level was normal in both the study & the control groups.

  2. Evaluation of a type 1 diabetes serum cohort by SELDI-TOF MS protein profiling

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Kaas, Anne; Schönle, Eugen

    2009-01-01

    -2002). Samples collected 1 (n = 270), 6 (n = 248), and 12 (n = 248) months after T1D diagnosis were grouped across centers and compared. The serum protein profiles varied with collection site and day of analysis; however, markers of sample processing were not systematically different between samples collected......Proteomics analysis of serum from patients with type 1 diabetes (T1D) may lead to novel biomarkers for prediction of disease and for patient monitoring. However, the serum proteome is highly sensitive to sample processing and before proteomics biomarker research serum cohorts should preferably...... be examined for potential bias between sample groups. SELDI-TOF MS protein profiling was used for preliminary evaluation of a biological-bank with 766 serum samples from 270 patients with T1D, collected at 18 different paediatric centers representing 15 countries in Europe and Japan over 2 years (2000...

  3. Biomarkers of Exposure to Triclocarban in Urine and Serum

    OpenAIRE

    Ye, Xiaoyun; Zhou, Xiaoliu; Furr, Johnathan; Ahn, Ki Chang; Hammock, Bruce D.; Gray, Earl L.; Calafat, Antonia M.

    2011-01-01

    3, 4, 4’- Trichlorocarbanilide (triclocarban, TCC) is widely used as an antimicrobial agent in a variety of consumer and personal care products. TCC is considered a potential endocrine disruptor, but its potential toxic effects in humans are still largely unknown. Because of its widespread uses, the potential for human exposure to TCC is high. In order to identify adequate exposure biomarkers of TCC, we investigated the metabolic profile of TCC in adult female Sprague Dawley rats after admini...

  4. Serum Biomarkers Identification by Mass Spectrometry in High-Mortality Tumors

    Directory of Open Access Journals (Sweden)

    Alessandra Tessitore

    2013-01-01

    Full Text Available Cancer affects millions of people worldwide. Tumor mortality is substantially due to diagnosis at stages that are too late for therapies to be effective. Advances in screening methods have improved the early diagnosis, prognosis, and survival for some cancers. Several validated biomarkers are currently used to diagnose and monitor the progression of cancer, but none of them shows adequate specificity, sensitivity, and predictive value for population screening. So, there is an urgent need to isolate novel sensitive, specific biomarkers to detect the disease early and improve prognosis, especially in high-mortality tumors. Proteomic techniques are powerful tools to help in diagnosis and monitoring of treatment and progression of the disease. During the last decade, mass spectrometry has assumed a key role in most of the proteomic analyses that are focused on identifying cancer biomarkers in human serum, making it possible to identify and characterize at the molecular level many proteins or peptides differentially expressed. In this paper we summarize the results of mass spectrometry serum profiling and biomarker identification in high mortality tumors, such as ovarian, liver, lung, and pancreatic cancer.

  5. Deciphering systemic lupus erythematosus-associated serum biomarkers reflecting apoptosis and disease activity.

    Science.gov (United States)

    Delfani, P; Sturfelt, G; Gullstrand, B; Carlsson, A; Kassandra, M; Borrebaeck, C A K; Bengtsson, A A; Wingren, C

    2017-04-01

    Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of potential autoantigen(s); however, the lack of disease-specific protein signatures deciphering SLE and the underlying biological processes is striking and represents a key limitation. In this retrospective pilot study, we explored the immune system as a specific sensor for disease, in order to advance our understanding of SLE. To this end, we determined multiplexed serum protein expression profiles of crude SLE serum samples, using antibody microarrays. The aim was to identify differential immunoprofiles, or snapshots of the immune response modulated by the disease, reflecting apoptosis, a key process in the etiology of SLE and disease activity. The results showed that multiplexed panels of SLE-associated serum biomarkers could be decoded, in particular reflecting disease activity, but potentially the apoptosis process as well. While the former biomarkers could display a potential future use for prognosis, the latter biomarkers might help shed further light on the apoptosis process taking place in SLE.

  6. PROFILEing idiopathic pulmonary fibrosis: rethinking biomarker discovery

    Directory of Open Access Journals (Sweden)

    Toby M. Maher

    2013-06-01

    Full Text Available Despite major advances in the understanding of the pathogenesis of idiopathic pulmonary fibrosis (IPF, diagnosis and management of the condition continue to pose significant challenges. Clinical management of IPF remains unsatisfactory due to limited availability of effective drug therapies, a lack of accurate indicators of disease progression, and an absence of simple short-term measures of therapeutic response. The identification of more accurate predictors of prognosis and survival in IPF would facilitate counseling of patients and their families, aid communication among clinicians, and would guide optimal timing of referral for transplantation. Improvements in molecular techniques have led to the identification of new disease pathways and a more targeted approach to the development of novel anti-fibrotic agents. However, despite an increased interest in biomarkers of IPF disease progression there are a lack of measures that can be used in early phase clinical trials. Careful longitudinal phenotyping of individuals with IPF together with the application of novel omics-based technology should provide important insights into disease pathogenesis and should address some of the major issues holding back drug development in IPF. The PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints study is a currently enrolling, prospective cohort study designed to tackle these issues.

  7. Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections

    OpenAIRE

    Krut, JJ; Zetterberg, H.; Blennow, K.; Cinque, P.; Hagberg, L; Price, Rw; Studahl, M; Gisslén, M.

    2013-01-01

    The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ 1-42 ), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amylo...

  8. Target biomarker profile for the clinical management of paracetamol overdose

    Science.gov (United States)

    Vliegenthart, A D Bastiaan; Antoine, Daniel J; Dear, James W

    2015-01-01

    Paracetamol (acetaminophen) overdose is one of the most common causes of acute liver injury in the Western world. To improve patient care and reduce pressure on already stretched health care providers new biomarkers are needed that identify or exclude liver injury soon after an overdose of paracetamol is ingested. This review highlights the current state of paracetamol poisoning management and how novel biomarkers could improve patient care and save healthcare providers money. Based on the widely used concept of defining a target product profile, a target biomarker profile is proposed that identifies desirable and acceptable key properties for a biomarker in development to enable the improved treatment of this patient population. The current biomarker candidates, with improved hepatic specificity and based on the fundamental mechanistic basis of paracetamol-induced liver injury, are reviewed and their performance compared with our target profile. PMID:26076366

  9. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

    Science.gov (United States)

    Sharman, Matthew J; Kraemer, William J; Love, Dawn M; Avery, Neva G; Gómez, Ana L; Scheett, Timothy P; Volek, Jeff S

    2002-07-01

    Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

  10. Profiling the Serum Albumin Cys34 Adductome of Solid Fuel Users in Xuanwei and Fuyuan, China

    NARCIS (Netherlands)

    Lu, Sixin S; Grigoryan, Hasmik; Edmands, William M B; Hu, Wei; Iavarone, Anthony T; Hubbard, Alan E.; Rothman, Nathaniel; Vermeulen, Roel|info:eu-repo/dai/nl/216532620; Lan, Qing; Rappaport, Stephen M.

    2017-01-01

    Xuanwei and Fuyuan counties in China have the highest lung cancer rates in the world due to household air pollution from combustion of smoky coal for cooking and heating. To discover potential biomarkers of indoor combustion products, we profiled adducts at the Cys34 locus of human serum albumin

  11. Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Shao Qing

    2014-11-01

    Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

  12. Validation of Candidate Serum Ovarian Cancer Biomarkers for Early Detection

    Directory of Open Access Journals (Sweden)

    Feng Su

    2007-01-01

    Full Text Available Objective: We have previously analyzed protein profi les using Surface Enhanced Laser Desorption and Ionization Time-Of-Flight Mass Spectroscopy (SELDI-TOF-MS [Kozak et al. 2003, Proc. Natl. Acad. Sci. U.S.A. 100:12343–8] and identified 3 differentially expressed serum proteins for the diagnosis of ovarian cancer (OC [Kozak et al. 2005, Proteomics, 5:4589–96], namely, apolipoprotein A-I (apoA-I, transthyretin (TTR and transferin (TF. The objective of the present study is to determine the efficacy of the three OC biomarkers for the detection of early stage (ES OC, in direct comparison to CA125.Methods: The levels of CA125, apoA-I, TTR and TF were measured in 392 serum samples [82 women with normal ovaries (N, 24 women with benign ovarian tumors (B, 85 women with ovarian tumors of low malignant potential (LMP, 126 women with early stage ovarian cancer (ESOC, and 75 women with late stage ovarian cancer (LSOC], obtained through the GOG and Cooperative Human Tissue Network. Following statistical analysis, multivariate regression models were built to evaluate the utility of the three OC markers in early detection.Results: Multiple logistic regression models (MLRM utilizing all biomarker values (CA125, TTR, TF and apoA-I from all histological subtypes (serous, mucinous, and endometrioid adenocarcinoma distinguished normal samples from LMP with 91% sensitivity (specifi city 92%, and normal samples from ESOC with a sensitivity of 89% (specifi city 92%. MLRM, utilizing values of all four markers from only the mucinous histological subtype showed that collectively, CA125, TTR, TF and apoA-I, were able to distinguish normal samples from mucinous LMP with 90% sensitivity, and further distinguished normal samples from early stage mucinous ovarian cancer with a sensitivity of 95%. In contrast, in serum samples from patients with mucinous tumors, CA125 alone was able to distinguish normal samples from LMP and early stage ovarian cancer with a sensitivity of

  13. The Janus serum bank and biomarkers of cancer

    Directory of Open Access Journals (Sweden)

    Randi Gislefoss

    2009-10-01

    Full Text Available The Janus serum bank, established in 1973, contains sera stored at –25 degrees collected from 330,000 originally healthy individuals. The number of cancer cases have increased from zero in 1973 to more than 50,000 in 2005, including invasive and non-invasive cancers. Information on cases have been obtained by coupling the Janus file against the Norwegian Cancer Registry. The sera have been used in over 70 different cancers research projects, usually in case-control studies and in collaboration with national and international research groups. The type of biomarker analysed include antibodies against Chlamydia, CMV, Epstein Barr virus, HPV and Helicobacter pylori. Leptin, long chain fatty acids, androgens and other hormones, vitamins as well as environmental toxins such as organochlorines are other types of cancer biomarkers investigated. Mutation analyses (BRCA-1 etc have been possible using PCR and the trace amounts of DNA remaining in the sera.Janus serum bank ble etablert i 1973 og inneholder sera lagret ved –25 grader, innsamlet fra 330.000 opprinnelig friske personer. Antall krefttilfeller har steget fra null i 1973 til over 50.000 i år 2005, inkludert både invasiv og ikke-invasiv kreft. Informasjon om kasus er tilgjengelig ved å koble Janus-filene mot Kreftregisterets databaser. Serumprøvene er blitt benyttet i over 70 forskjellige kreftforskningsprosjekter, som oftest i kasus-kontroll studier og i samarbeide med en rekke nasjonale og internasjonale forskningsgrupper. Mange ulike biomarkører på kreft er blitt analysert, bl.a. antistoffer mot Chlamydia, CMV, Epstein Barr virus, HPV og Helicobacter pylori. Leptin, lange fettsyrer, androgener og andre hormoner, vitaminer såvel som miljøgifter av typen organiske klorforbindelser er eksempler på andre kreftbiomarkører som er undersøkt. Det har også vært mulig å gjøre mutasjonsanalyser (BRCA-1 etc ved å bruke PCR til å amplifisere opp den spormengden DNA som finnes i serum.

  14. Serum protein biomarkers relevant to hepatocellular carcinoma and their detection.

    Science.gov (United States)

    Waidely, Eric; Al-Yuobi, Abdul-Rahman Obaid; Bashammakh, A S; El-Shahawi, Mohammad S; Leblanc, Roger M

    2016-01-07

    Hepatocellular carcinoma (HCC) is one of the most recurrent and lethal cancers worldwide. The low survival rate of this particular strain of carcinoma is largely due to the late stages at which it is diagnosed. Tumorigenesis of hepatocellular carcinoma is most frequently detected through ultrasonography, magnetic resonance imaging and computerized tomography scans, however, these methods are poor for detection of early tumor development. This review presents alternative hepatocellular carcinoma detection techniques through the use of protein and enzyme/isozyme biomarkers. The detection methods used to determine the serum levels of α-fetoprotein (AFP), glypican-3 (GPC3), Golgi protein 73 (GP73), α-L-fucosidase (AFU), des-γ-carboxyprothrombin (DCP), γ-glutamyl transferase (GGT) and squamous cell carcinoma antigen (SCCA) are presented and each marker's respective validity in the diagnosis of hepatocellular carcinoma is evaluated.

  15. Serum proteomic profiles of depressive subtypes.

    Science.gov (United States)

    Lamers, F; Bot, M; Jansen, R; Chan, M K; Cooper, J D; Bahn, S; Penninx, B W J H

    2016-07-12

    Depression is a highly heterogeneous disorder. Accumulating evidence suggests biological and genetic differences between subtypes of depression that are homogeneous in symptom presentation. We aimed to evaluate differences in serum protein profiles between persons with atypical and melancholic depressive subtypes, and compare these profiles with serum protein levels of healthy controls. We used the baseline data from the Netherlands Study of Depression and Anxiety on 414 controls, 231 persons with a melancholic depressive subtype and 128 persons with an atypical depressive subtype for whom the proteomic data were available. Depressive subtypes were previously established using a data-driven analysis, and 171 serum proteins were measured on a multi-analyte profiling platform. Linear regression models were adjusted for several covariates and corrected for multiple testing using false discovery rate q-values. We observed differences in analytes between the atypical and melancholic subtypes (9 analytes, q<0.05) and between atypical depression and controls (23 analytes, q<0.05). Eight of the nine markers differing between the atypical and melancholic subtype overlapped with markers from the comparison between atypical subtype and controls (mesothelin, leptin, IGFBP1, IGFBP2, FABPa, insulin, C3 and B2M), and were mainly involved in cellular communication and signal transduction, and immune response. No markers differed significantly between the melancholic subtype and controls. To conclude, although some uncertainties exist in our results as a result of missing data imputation and lack of proteomic replication samples, many of the identified analytes are inflammatory or metabolic markers, which supports the notion of atypical depression as a syndrome characterized by metabolic disturbances and inflammation, and underline the importance and relevance of subtypes of depression in biological and genetic research, and potentially in the treatment of depression.

  16. Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Høgdall, Estrid

    2010-01-01

    The purposes of this study were to confirm previously found candidate epithelial ovarian cancer biomarkers in urine and to compare a paired serum biomarker panel and a urine biomarker panel from the same study cohort with regard to the receiver operating characteristic curve (ROC) area under the ...

  17. Comparison of proteomic biomarker panels in urine and serum for ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Simonsen, Anja Hviid; Høgdall, Estrid

    2010-01-01

    The purposes of this study were to confirm previously found candidate epithelial ovarian cancer biomarkers in urine and to compare a paired serum biomarker panel and a urine biomarker panel from the same study cohort with regard to the receiver operating characteristic curve (ROC) area under...... the ROC curve (AUC) values....

  18. Serum adipokines as biomarkers of beta-cell function in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Pham, Minh Nguyet; Kolb, Hubert; Mandrup-Poulsen, Thomas

    2013-01-01

    We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes.......We investigated the adipokines adiponectin, leptin and resistin as serum biomarkers of beta-cell function in patients with type 1 diabetes....

  19. Exploration of candidate biomarkers for human psoriasis based on gas chromatography-mass spectrometry serum metabolomics.

    Science.gov (United States)

    Kang, H; Li, X; Zhou, Q; Quan, C; Xue, F; Zheng, J; Yu, Y

    2017-03-01

    Recent studies have shown that dysregulated metabolic pathways are linked to psoriasis pathogenesis. However, an extensive, unbiased metabolic analysis in patients with psoriasis has not been completely explored. The metabolome represents the end products of proteomics or cellular processes that may be closely associated with the pathogenesis of psoriasis. To determine the differences in serum metabolomic profiles among patients with psoriasis and healthy controls with the goal of identifying potential biomarkers in patients with psoriasis. Serum metabolomic profiles from 29 subjects (14 patients with psoriasis and 15 sex- and age-matched healthy controls). The serum metabolites were analysed by gas chromatography-mass spectrometry based on a combined full scan and selected-ion monitoring mode. Multivariate statistical analysis of metabolomics data revealed altered serum metabolites between the patients with psoriasis and healthy individuals. Compared with healthy individuals, patients with psoriasis had higher levels of amino acids including asparagine, aspartic acid, isoleucine, phenylalanine, ornithine and proline; higher levels of lactic acid and urea; and lower levels of crotonic acid, azelaic acid, ethanolamine and cholesterol. It appears that the glycolysis pathway and amino acid metabolic activity are increased in patients with psoriasis. These metabolic perturbations may stem from increased demand for protein biosynthesis and keratinocyte hyperproliferation. Our findings may help to elucidate the pathogenesis of psoriasis and provide insights into early diagnosis and therapeutic intervention. © 2016 British Association of Dermatologists.

  20. Early Second-Trimester Serum MicroRNAs as Potential Biomarker for Nondiabetic Macrosomia

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    Lingmin Hu

    2014-01-01

    Full Text Available Background. Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. Methods. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. Results. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P=0.048 for miR-194 and P=0.018 for miR-376a, resp.. Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P=0.032. Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity = 96.7% and specificity = 40.0%. Conclusions. Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.

  1. Early second-trimester serum microRNAs as potential biomarker for nondiabetic macrosomia.

    Science.gov (United States)

    Hu, Lingmin; Han, Jing; Zheng, Fangxiu; Ma, Hongxia; Chen, Jiaping; Jiang, Yue; Jiang, Hua

    2014-01-01

    Macrosomia has become a worldwide problem with the rapid economic growth in the past few years. However, the detailed mechanism of how the macrosomia happened remains unknown. Growing evidence indicates that miRNAs are involved in maintaining metabolic homeostasis. We hypothesized that serum miRNAs are potential biomarkers for macrosomia. We performed miRNAs profiling using TLDA chips in the discovery phase in two pooled samples from 30 cases and 30 controls, respectively. Individual qRT-PCR was conducted for the discovery phase samples. To confirm the results, we detected the miRNAs which were differentially expressed in the microarray assays and individual qRT-PCR in external validation phase with another 30 cases and 30 controls. In the discovery stage, miR-194 and miR-376a expression levels were significantly different between macrosomia group and controls (P=0.048 for miR-194 and P=0.018 for miR-376a, resp.). Further evaluation of the two miRNAs on a total of 120 serum samples showed that the miR-376a remains significantly lower in macrosomia (P=0.032). Receiver operating characteristic curve analyses showed that the area under curve for miR-376a was 67.8% (sensitivity=96.7% and specificity=40.0%). Serum miR-376a may serve as a potential noninvasive biomarker in detecting macrosomia.

  2. Biomarker identification and pathway analysis of preeclampsia based on serum metabolomics.

    Science.gov (United States)

    Chen, Tingting; He, Ping; Tan, Yong; Xu, Dongying

    2017-03-25

    Preeclampsia presents serious risk of both maternal and fetal morbidity and mortality. Biomarkers for the detection of preeclampsia are critical for risk assessment and targeted intervention. The goal of this study is to screen potential biomarkers for the diagnosis of preeclampsia and to illuminate the pathogenesis of preeclampsia development based on the differential expression network. Two groups of subjects, including healthy pregnant women, subjects with preeclampsia, were recruited for this study. The metabolic profiles of all of the subjects' serum were obtained by liquid chromatography quadruple time-of-flight mass spectrometry. Correlation between metabolites was analyzed by bioinformatics technique. Results showed that the PC(14:0/00), proline betaine and proline were potential sensitive and specific biomarkers for preeclampsia diagnosis and prognosis. Perturbation of corresponding biological pathways, such as iNOS signaling, nitric oxide signaling in the cardiovascular system, mitochondrial dysfunction were responsible for the pathogenesis of preeclampsia. This study indicated that the metabolic profiling had a good clinical significance in the diagnosis of preeclampsia as well as in the study of its pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Copeptin as a serum biomarker of febrile seizures.

    Directory of Open Access Journals (Sweden)

    Benjamin Stöcklin

    Full Text Available Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion.This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment.NCT01884766.Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6] compared to febrile controls (5.6 pmol/L [4.1-9.4]; p < 0.001, with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728. In a multivariable regression model, seizures were the major determinant of serum copeptin (beta 0.509; p < 0.001, independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881, significantly higher compared to prolactin (0.667 [0.585-0.742]; p < 0.001. The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997].Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting.

  4. Comparison of Peripheral and Central Schizophrenia Biomarker Profiles

    NARCIS (Netherlands)

    L.W. Harris (Laura); S. Pietsch (Sandra); T.M.K. Cheng (Tammy); E. Schwarz (Emanuel); P.C. Guest (Paul); S. Bahn (Sabine)

    2012-01-01

    textabstractWe have recently shown that a molecular biomarker signature comprised of inflammatory, hormonal and growth factors occurs in the blood serum from first onset schizophrenia patients. Here, we use the same platform to investigate post mortem brain tissue (Brodmann area 10) from

  5. Deciphering Asthma Biomarkers with Protein Profiling Technology

    Directory of Open Access Journals (Sweden)

    Zhizhou Kuang

    2015-01-01

    Full Text Available Asthma is a chronic inflammatory disease of the airways, resulting in bronchial hyperresponsiveness with every allergen exposure. It is now clear that asthma is not a single disease, but rather a multifaceted syndrome that results from a variety of biologic mechanisms. Asthma is further problematic given that the disease consists of many variants, each with its own etiologic and pathophysiologic factors, including different cellular responses and inflammatory phenotypes. These facets make the rapid and accurate diagnosis (not to mention treatments of asthma extremely difficult. Protein biomarkers can serve as powerful detection tools in both clinical and basic research applications. Recent endeavors from biomedical researchers have developed technical platforms, such as cytokine antibody arrays, that have been employed and used to further the global analysis of asthma biomarker studies. In this review, we discuss potential asthma biomarkers involved in the pathophysiologic process and eventual pathogenesis of asthma, how these biomarkers are being utilized, and how further testing methods might help improve the diagnosis and treatment strain that current asthma patients suffer.

  6. Differentially expressed RNA from public microarray data identifies serum protein biomarkers for cross-organ transplant rejection and other conditions.

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    Rong Chen

    2010-09-01

    Full Text Available Serum proteins are routinely used to diagnose diseases, but are hard to find due to low sensitivity in screening the serum proteome. Public repositories of microarray data, such as the Gene Expression Omnibus (GEO, contain RNA expression profiles for more than 16,000 biological conditions, covering more than 30% of United States mortality. We hypothesized that genes coding for serum- and urine-detectable proteins, and showing differential expression of RNA in disease-damaged tissues would make ideal diagnostic protein biomarkers for those diseases. We showed that predicted protein biomarkers are significantly enriched for known diagnostic protein biomarkers in 22 diseases, with enrichment significantly higher in diseases for which at least three datasets are available. We then used this strategy to search for new biomarkers indicating acute rejection (AR across different types of transplanted solid organs. We integrated three biopsy-based microarray studies of AR from pediatric renal, adult renal and adult cardiac transplantation and identified 45 genes upregulated in all three. From this set, we chose 10 proteins for serum ELISA assays in 39 renal transplant patients, and discovered three that were significantly higher in AR. Interestingly, all three proteins were also significantly higher during AR in the 63 cardiac transplant recipients studied. Our best marker, serum PECAM1, identified renal AR with 89% sensitivity and 75% specificity, and also showed increased expression in AR by immunohistochemistry in renal, hepatic and cardiac transplant biopsies. Our results demonstrate that integrating gene expression microarray measurements from disease samples and even publicly-available data sets can be a powerful, fast, and cost-effective strategy for the discovery of new diagnostic serum protein biomarkers.

  7. Evaluation of full-length, cleaved and nitrosylated serum surfactant protein D as biomarkers for COPD

    DEFF Research Database (Denmark)

    Duvoix, Annelyse; Miranda, Elena; Perez, Juan

    2011-01-01

    . Serum levels of SP-D are raised in individuals with COPD but there is no correlation between the serum level of SP-D and the severity of airflow obstruction. Serum SP-D is present in different forms that may have more utility as a biomarker for COPD. We report here the development of new monoclonal...

  8. Elucidating novel serum biomarkers associated with pulmonary tuberculosis treatment.

    Directory of Open Access Journals (Sweden)

    Mary A De Groote

    Full Text Available In an unbiased approach to biomarker discovery, we applied a highly multiplexed proteomic technology (SOMAscan, SomaLogic, Inc, Boulder, CO to understand changes in proteins from paired serum samples at enrollment and after 8 weeks of TB treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in the Center for Disease Control and Prevention's Tuberculosis Trials Consortium (TBTC Study 29. This work represents the first large-scale proteomic analysis employing modified DNA aptamers in a study of active tuberculosis (TB. We identified multiple proteins that exhibit significant expression differences during the intensive phase of TB therapy. There was enrichment for proteins in conserved networks of biological processes and function including antimicrobial defense, tissue healing and remodeling, acute phase response, pattern recognition, protease/anti-proteases, complement and coagulation cascade, apoptosis, immunity and inflammation pathways. Members of cytokine pathways such as interferon-gamma, while present, were not as highly represented as might have been predicted. The top proteins that changed between baseline and 8 weeks of therapy were TSP4, TIMP-2, SEPR, MRC-2, Antithrombin III, SAA, CRP, NPS-PLA2, LEAP-1, and LBP. The novel proteins elucidated in this work may provide new insights for understanding TB disease, its treatment and subsequent healing processes that occur in response to effective therapy.

  9. Serological Investigation And Interpreting Serum Chemistry Profile ...

    African Journals Online (AJOL)

    From the above number of samples 20 serum samples only are used as infected group and 20 serum samples from clinically healthy animals considered as control group. Serum samples were used to establish the concentration of total protein, albumin, glucose, total cholesterol, calcium and phosphorus. Serum nitrate ...

  10. Serum decoy receptor 3 is a biomarker for disease severity in nonatopic asthma patients

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    Ming-Han Chen

    2017-01-01

    Conclusion: High serum DcR3 levels are associated with disease severity in nonatopic asthma patients, which suggests that DcR3 is a potential biomarker that can be used to predict the severity of nonatopic asthma.

  11. Use of Serum MicroRNAs as Biomarker for Hepatobiliary Diseases in Dogs

    NARCIS (Netherlands)

    Dirksen, K; Verzijl, T; Grinwis, G C; Favier, R P; Penning, L C; Burgener, I A; van der Laan, L J; Fieten, H; Spee, B

    2016-01-01

    BACKGROUND: Current biochemical indicators cannot discriminate between parenchymal, biliary, vascular, and neoplastic hepatobiliary diseases. MicroRNAs are promising new biomarkers for hepatobiliary disease in humans and dogs. OBJECTIVE: To measure serum concentrations of an established group of

  12. Identification of New Serum Biomarkers for Early Breast Cancer Diagnosis and Prognosis Using Lipid Microarrays

    National Research Council Canada - National Science Library

    Du, Guangwei

    2008-01-01

    Breast cancer is the most common form of cancer among women. Compared with other serum polypeptides, autoantibodies have many appealing features as biomarkers including sensitivity, stability, and easy detection...

  13. Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

    Directory of Open Access Journals (Sweden)

    Qi Yuhua

    2012-12-01

    Full Text Available Abstract Background Pulmonary tuberculosis (TB is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP, varicella-zoster virus (VZV and enterovirus (EV were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated. Following qRT-PCR confirmation and receiver operational curve (ROC analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC value range, 0.711-0.848. Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection.

  14. Serum microRNAs as potential biomarkers of primary biliary cirrhosis.

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    Youwen Tan

    Full Text Available Circulating microRNAs (miRNAs, which are extremely stable and protected from RNAse-mediated degradation in body fluids, have emerged as candidate biomarkers for many diseases. The present study aimed to identify a serum microRNA (miRNA expression profile that could serve as a novel diagnostic biomarker for primary biliary cirrhosis (PBC.Serum miRNA expression was investigated using four cohorts comprising 380 participants (healthy controls and patients with PBC recruited between August 2010 and June 2013. miRNA expression was initially analyzed by Illumina sequencing using serum samples pooled from 3 patients and 3 controls. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR was then used to evaluate the expression of selected miRNAs in a screening set (n = 40. A logistic regression model was then constructed using a training cohort (n = 192 and validated using another cohort (n = 142. The area under the receiver operating characteristic curve (AUC was used to evaluate diagnostic accuracy.We identified a miRNA panel (hsa-miR-122-5p, hsa-miR-141-3p, and hsa-miR-26b-5p with a high diagnostic accuracy for PBC (AUC = 0.905, 95% confidence interval (CI = 0.857 to 0.953; sensitivity = 80.5%, specificity = 88.3%. There was a significant difference between AUC values of the miRNA panel and those of alkaline phosphatase (ALP (AUC = 0.537, difference between areas = 0.314, 95% CI = 0.195 to 0.434, P<0.001, and those of antinuclear antibody (ANA (AUC = 0.739, difference between areas = 0.112, 95% CI = 0.012 to 0.213, P = 0.0282.We identified a serum microRNA panel with considerable clinical value in PBC diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for PBC than ALP and ANA.

  15. Serum Antibody Repertoire Profiling Using In Silico Antigen Screen.

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    Xinyue Liu

    Full Text Available Serum antibodies are valuable source of information on the health state of an organism. The profiles of serum antibody reactivity can be generated by using a high throughput sequencing of peptide-coding DNA from combinatorial random peptide phage display libraries selected for binding to serum antibodies. Here we demonstrate that the targets of immune response, which are recognized by serum antibodies directed against sequential epitopes, can be identified using the serum antibody repertoire profiles generated by high throughput sequencing. We developed an algorithm to filter the results of the protein database BLAST search for selected peptides to distinguish real antigens recognized by serum antibodies from irrelevant proteins retrieved randomly. When we used this algorithm to analyze serum antibodies from mice immunized with human protein, we were able to identify the protein used for immunizations among the top candidate antigens. When we analyzed human serum sample from the metastatic melanoma patient, the recombinant protein, corresponding to the top candidate from the list generated using the algorithm, was recognized by antibodies from metastatic melanoma serum on the western blot, thus confirming that the method can identify autoantigens recognized by serum antibodies. We demonstrated also that our unbiased method of looking at the repertoire of serum antibodies reveals quantitative information on the epitope composition of the targets of immune response. A method for deciphering information contained in the serum antibody repertoire profiles may help to identify autoantibodies that can be used for diagnosing and monitoring autoimmune diseases or malignancies.

  16. Original Article : Correlation between preoperative serum Levels of five biomarkers and relationships between these biomarkers and cancer stage in epithelial overian cancer

    National Research Council Canada - National Science Library

    Jong Yun Hwang; ; Sung Hun Na; Hyang Ah Lee; Dong Heon Lee

    2009-01-01

    Objective: To examine the correlation among the preoperative serum levels of five biomarkers presumed to be useful for early detection of epithelial ovarian cancer and evaluate the relationships between serum...

  17. Identification of overexpressed cytokines as serum biomarkers of ...

    African Journals Online (AJOL)

    Hepatic inflammation is the stimulator to activate hepatic stellate cells (HSCs) and triggers fibrogenesis. Cytokines are produced during liver inflammation and maybe considered as liver fibrosis biomarker. The aim of this study was to investigate whether cytokines can be used as reliable biomarkers of liver fibrosis using ...

  18. Profiling of serum and urinary microRNAs in children with atopic dermatitis.

    Science.gov (United States)

    Lv, Yani; Qi, Ruiqun; Xu, Jing; Di, Zhenghong; Zheng, Heng; Huo, Wei; Zhang, Li; Chen, Hongduo; Gao, Xinghua

    2014-01-01

    Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Serum and urine from 30 children with AD and 28 healthy children were collected and their genome-wide miRNA expression profiles were measured by TaqMan-based array and confirmed by quantitative real-time PCR. Inflammatory factors in serum were detected by Antibody Array System. miR-203 and miR-483-5p were significantly up-regulated in serum of children with AD compared with healthy children. The level of miR-483-5p in serum was significantly associated with other atopic conditions, such as rhinitis and/or asthma. However, miR-203 was markedly decreased in urine of children with AD compared with healthy children. Down-regulated miR-203 in urine was significant associated with abnormal level of serum IgE in AD patients. 7 inflammatory factors in serum were altered in children with AD compared with healthy children. Up-regulated miR-203 in serum was significantly associated with increased sTNFRI and sTNFRII. Up-regulated miR-483-5p in serum may be indicative of other atopic conditions in children with AD. Down-regulated miR-203 in urine may serve as a biomarker for the severity of inflammation in children with AD.

  19. Serum Biomarkers for the Diagnosis of Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

    Science.gov (United States)

    Ishihara, Shunji; Shoda, Tetsuo; Ishimura, Norihisa; Ohta, Shoichiro; Ono, Junya; Azuma, Yoshinori; Okimoto, Eiko; Izuhara, Kenji; Nomura, Ichiro; Matsumoto, Kenji; Kinoshita, Yoshikazu

    2017-11-01

    Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3β/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.

  20. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

    Science.gov (United States)

    Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2015-01-01

    Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

  1. Serum biomarkers predictive of cure in Chagas disease patients after nifurtimox treatment.

    Science.gov (United States)

    Santamaria, Cynthia; Chatelain, Eric; Jackson, Yves; Miao, Qianqian; Ward, Brian J; Chappuis, François; Ndao, Momar

    2014-06-03

    Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, remains an important public health issue in many Central and South American countries, as well as non-endemic areas with high rates of immigration from these countries. Existing treatment options for CD are limited and often unsatisfactory. Moreover the lack of post-treatment tests of cure limits the development of new drugs. To address this issue, we sought to identify serum biomarkers following nifurtimox (Nfx) treatment that could be used as an early test of cure and/or markers of a therapeutic response. Human sera from Chagas patients pre- and post-treatment with Nfx (n = 37) were compared to samples from healthy subjects (n = 37) using a range of proteomic and immunologic techniques. Biomarker peaks with the best discriminatory power were further characterized. Using serum samples (n = 111), we validated the presence of five key biomarkers identified in our previous study, namely human apolipoprotein A-I (APOA1) and specific fragments thereof and one fragment of human fibronectin (FN1). In chagasic serum samples all biomarkers except full-length APOA1 were upregulated. These five biomarkers returned to normal in 43% (16/37) of the patients treated with Nfx at three years after treatment. The normalization of biomarker patterns strongly associated with CD suggests that these markers can be used to identify patients in whom Nfx treatment is successful. We believe that these are the first biomarkers predictive of cure in CD patients.

  2. CEACAM1 and MICA as novel serum biomarkers in patients with acute and recurrent pericarditis.

    Science.gov (United States)

    Markel, Gal; Imazio, Massimo; Koren-Morag, Nira; Galore-Haskel, Gilli; Schachter, Jacob; Besser, Michal; Cumetti, Davide; Maestroni, Silvia; Altman, Arie; Shoenfeld, Yehuda; Brucato, Antonio; Adler, Yehuda

    2016-04-05

    The immune response plays a significant role in pericarditis, but the mechanisms of disease are poorly defined. Further, efficient monitoring and predictive clinical tools are unavailable. Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is an immune-inhibitory protein, while MHC class I chain related protein A (MICA) and B (MICB) have an immune-stimulating function. Serum CEACAM1, MICA and MICB concentrations were measured by ELISA in ~50 subjects of each group: acute pericarditis (AP), recurrent pericarditis (RP) and lupus (SLE) patients, metastatic melanoma patients as well as healthy donors. Serum CEACAM1 was dramatically elevated in AP and RP patients, but not in SLE patients, and displayed a highly accurate profile in ROC curve analyses. MICA and MICB were elevated in some pericarditis patients. All markers were enhanced in metastatic melanoma patients irrespective of neoplastic pericardial involvement. Etiology-guided analysis of RP patients showed that very low MICA levels were associated with idiopathic RP, while high MICA was associated with autoimmune and post-operative RP. Importantly, MICA was significantly associated with recurrences, independently of other potentially confounding parameters such as age, time of follow up or treatment modality. Here we report for the first time on CEACAM1 as a potentially novel biomarker for pericarditis, as well as on MICA as an innovative prognostic marker in these patients. Determination of the roles of these immune factors, as well as their diagnostic and prognostic values should be determined in future prospective studies.

  3. Serum Collagen Type II Cleavage Epitope and Serum Hyaluronic Acid as Biomarkers for Treatment Monitoring of Dogs with Hip Osteoarthritis.

    Science.gov (United States)

    Vilar, José M; Rubio, Mónica; Spinella, Giuseppe; Cuervo, Belén; Sopena, Joaquín; Cugat, Ramón; Garcia-Balletbó, Montserrat; Dominguez, Juan M; Granados, Maria; Tvarijonaviciute, Asta; Ceron, José J; Carrillo, José M

    2016-01-01

    The aim of this study was to evaluate the use of serum type II collagen cleavage epitope and serum hyaluronic acid as biomarkers for treatment monitoring in osteoarthritic dogs. For this purpose, a treatment model based on mesenchymal stem cells derived from adipose tissue combined with plasma rich in growth factors was used. This clinical study included 10 dogs with hip osteoarthritis. Both analytes were measured in serum at baseline, just before applying the treatment, and 1, 3, and 6 months after treatment. These results were compared with those obtained from force plate analysis using the same animals during the same study period. Levels of type II collagen cleavage epitope decreased and those of hyaluronic acid increased with clinical improvement objectively verified via force plate analysis, suggesting these two biomarkers could be effective as indicators of clinical development of joint disease in dogs.

  4. Serum proteomic profiling of major depressive disorder

    National Research Council Canada - National Science Library

    Bot, M; Chan, M.K; Jansen, R; Lamers, F; Vogelzangs, N; Steiner, J; Leweke, F.M; Rothermundt, M; Cooper, J; Bahn, S; Penninx, B.W.J.H

    2015-01-01

    Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD...

  5. Haematological and serum biochemical profiles of broiler chickens ...

    African Journals Online (AJOL)

    MOLM) on the haematological and serum biochemical profile of broiler chickens. Fresh Moringa leaves (FML) were shade-dried for four days and milled into meal. A total of two hundred broilers unsexed chickens (Anak strain) were randomly ...

  6. Serum lipid profile in diabetic and hypertensive Nigerian subjects ...

    African Journals Online (AJOL)

    ... to compare the serum lipid profile of diabetic and hypertensive subjects resident in Kano metropolis and to evaluate their pattern and probable disposition to atherosclerosis and coronary heart disease. ... Results: Hypertensive subjects had higher mean serum TC, HDL-CH, BMI and BP values that diabetic subjects.

  7. Serum protein expression profiling and bioinformatics analysis in workers occupationally exposed to chromium (VI).

    Science.gov (United States)

    Hu, Guiping; Wang, Tianjing; Liu, Jiaxing; Chen, Zhangjian; Zhong, Lijun; Yu, Shanfa; Zhao, Zuchang; Zhai, Min; Jia, Guang

    2017-08-05

    Cr(VI) is widely-recognized as occupational and environmental contaminant, but the precise underlying mechanisms of Cr(VI) induced carcinogenic toxicity remain to be elucidated. Among kinds of toxic mechanisms, alteration of protein profiling usually elaborate a key mechanism of Cr(VI) induced toxicity and carcinogenesis. Large-scale proteins changes can reflect the onset or progression of carcinogenic toxicity, and potential serum protein biomarkers of Cr(VI) exposure. To gain an insight into the serum proteins expression profiling in chromate workers and find potential novel serum proteins biomarkers of Cr(VI) exposure, 107 male participants from a chromate production plant were recruited into the study. Questionnaire was applied to collect personal information and occupational history. Chromium concentration in blood (CrB) was measured to evaluate the participants' internal exposure. Serum proteins profiling and bioinformatics analysis were performed to explore differentially expressed proteins, proteins-chemical interaction network, critical proteins nodes related to the signaling pathways among 16 controls and 25 exposure workers in the first stage. ELISA tests were applied to verify the critical interested proteins nodes in the remaining 41 exposure workers and 25 controls. The results showed that the CrB levels in the control group were significantly lower than that in the exposure group (P<0.05). 44 significantly differentially expressed serum proteins formed 16 significant signaling pathways and a complex proteins-chemical interaction network, which associated with the immune system and extracellular matrix organization. C reactive protein (CRP), sonic hedgehog protein (SHH) and calcium located at critical nodes in proteins-chemical interaction network. There was a significant negative correlation between serum CRP level and CrB (P<0.05), and a significant positive correlation between SHH concentrations and CrB (P<0.05), which indicated that CRP and SHH

  8. Detection of serum protein biomarkers by surface enhanced laser desorption/ionization in patients with adenocarcinoma of the lung.

    Science.gov (United States)

    Jiang, Min; Gu, Guohao; Ni, Bin; Wang, Wenjing; Shi, Jinfang; Liao, Ping; Hu, Heng

    2014-06-01

    Early diagnosis of lung cancer is important for successful treatment and improving the outcome of patients. We explored novel tools for screening serum biomarkers to distinguish adenocarcinoma of the lung from healthy controls by serum protein profiles. Serum samples were taken from 31 patients with adenocarcinoma of the lung and 31 healthy controls, matched for age, sex and smoking status. Serum samples were applied to strong anion 2(SAX-2) protein chips to generate mass spectra by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Protein peak identification and clustering were performed using Biomarker Wizard, compared by MATLAB 7.5 and a classification tree was constructed using R weka software. The validity of the classification tree was then challenged with a blind test. The software identified 102 peaks and m/z 14022.9 and m/z 3735.99 was used to construct a classification tree. The classification tree effectively separated adenocarcinoma of lung patients from healthy controls, achieving a validity of 100%. The blind test challenged the model with a sensitivity of 100% and a specificity of 100%. The results suggested that the SELDI-TOF-MS technique can correctly distinguish adenocarcinoma of lung patients from healthy controls and showed great potential for development as a screening test for the detection of lung cancer. © 2013 Wiley Publishing Asia Pty Ltd.

  9. Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis

    Science.gov (United States)

    Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid

    2017-01-01

    Abstract There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children. All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated. Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%). The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis. PMID:28858084

  10. Identification of overexpressed cytokines as serum biomarkers of ...

    African Journals Online (AJOL)

    Yomi

    discover differential biomarkers. Finally, levels of protein expressions of individual stages of liver fibrosis were measured. In histological examination, the necroinflammatory score ... liver cirrhosis or even hepatocellular carcinoma. Liver fibrosis is the process of repair when liver is injured or in inflammation (Marcellin, 1999).

  11. Evaluation of Serum and Urinary Neopterin Levels as a Biomarker ...

    African Journals Online (AJOL)

    Background: Crystalline silica is a commonly used mineral in various industries and construction activities, and it is so important introducing potential biomarkers to identify early indicators of biological effects in its high‑risk occupational exposures. Aim: The present study was aimed to assess the blood and urinary neopterin ...

  12. Magnetic resonance imaging and biomarkers of serum and urine wile diagnostics of kidney cancer

    Directory of Open Access Journals (Sweden)

    Nickolsky Yu.Ye.

    2016-03-01

    Full Text Available Purpose: improvement of differential diagnostics of benign and malignant renal tumors basing on complex estimation of the results of MRTand the level of such biomarkers as vascular endothelial growth factor, monocyte chemotactic protein-1 and matrix metalloproteinase-9 in blood serum and urine. Material and Methods. A total of 106 patients including the main group of 60 patients with renal cancer (RC, the group of comparison of 16 patients with benign renal tumors and the control group of 30 practically healthy persons were examined. ELISA was employed for detection of the biomarkers in blood serum and urine. The tumors were diagnosed by MRT Results. The increase of the level of the biomarkers in blood serum and urine was registered independently of the character of neoplastic process; more significant increase was observed in patients with RC, especially at the early stages of the disease. Some peculiarities of changing of the level of the biomarkers depending on the dimensions of malignant tumors were found. Conclusion. At the early stages of RC complex detection of the abovementioned biomarkers in blood serum and urine can serve an additional clinical diagnostic and prognostic criterion.

  13. Abnormalities in serum biomarkers correlate with lower cardiac index in the Fontan population.

    Science.gov (United States)

    Marino, Bradley S; Goldberg, David J; Dorfman, Adam L; King, Eileen; Kalkwarf, Heidi; Zemel, Babette S; Smith, Margaret; Pratt, Jesse; Fogel, Mark A; Shillingford, Amanda J; Deal, Barbara J; John, Anitha S; Goldberg, Caren S; Hoffman, Timothy M; Jacobs, Marshall L; Lisec, Asher; Finan, Susan; Kochilas, Lazaros K; Pawlowski, Thomas W; Campbell, Kathleen; Joiner, Clinton; Goldstein, Stuart L; Stephens, Paul; Chin, Alvin J

    2017-01-01

    Fontan survivors have depressed cardiac index that worsens over time. Serum biomarker measurement is minimally invasive, rapid, widely available, and may be useful for serial monitoring. The purpose of this study was to identify biomarkers that correlate with lower cardiac index in Fontan patients. Methods and results This study was a multi-centre case series assessing the correlations between biomarkers and cardiac magnetic resonance-derived cardiac index in Fontan patients ⩾6 years of age with biochemical and haematopoietic biomarkers obtained ±12 months from cardiac magnetic resonance. Medical history and biomarker values were obtained by chart review. Spearman's Rank correlation assessed associations between biomarker z-scores and cardiac index. Biomarkers with significant correlations had receiver operating characteristic curves and area under the curve estimated. In total, 97 cardiac magnetic resonances in 87 patients met inclusion criteria: median age at cardiac magnetic resonance was 15 (6-33) years. Significant correlations were found between cardiac index and total alkaline phosphatase (-0.26, p=0.04), estimated creatinine clearance (0.26, p=0.02), and mean corpuscular volume (-0.32, pbiomarkers was 0.63-0.69. Area under the curve for the three-biomarker panel was 0.75. Comparison of cardiac index above and below the receiver operating characteristic curve-identified cut-off points revealed significant differences for each biomarker (pbiomarkers to monitor haemodynamics and organ-specific effects warrants prospective investigation.

  14. Detection of cancer biomarkers in serum using a hybrid mechanical and optoplasmonic nanosensor

    Science.gov (United States)

    Kosaka, P. M.; Pini, V.; Ruz, J. J.; da Silva, R. A.; González, M. U.; Ramos, D.; Calleja, M.; Tamayo, J.

    2014-12-01

    Blood contains a range of protein biomarkers that could be used in the early detection of disease. To achieve this, however, requires sensors capable of detecting (with high reproducibility) biomarkers at concentrations one million times lower than the concentration of the other blood proteins. Here, we show that a sandwich assay that combines mechanical and optoplasmonic transduction can detect cancer biomarkers in serum at ultralow concentrations. A biomarker is first recognized by a surface-anchored antibody and then by an antibody in solution that identifies a free region of the captured biomarker. This second antibody is tethered to a gold nanoparticle that acts as a mass and plasmonic label; the two signatures are detected by means of a silicon cantilever that serves as a mechanical resonator for ‘weighing’ the mass of the captured nanoparticles and as an optical cavity that boosts the plasmonic signal from the nanoparticles. The capabilities of the approach are illustrated with two cancer biomarkers: the carcinoembryonic antigen and the prostate specific antigen, which are currently in clinical use for the diagnosis, monitoring and prognosis of colon and prostate cancer, respectively. A detection limit of 1 × 10-16 g ml-1 in serum is achieved with both biomarkers, which is at least seven orders of magnitude lower than that achieved in routine clinical practice. Moreover, the rate of false positives and false negatives at this concentration is extremely low, ˜10-4.

  15. Serum Lipid Profile: Fasting or Non-fasting?

    OpenAIRE

    Nigam, P. K.

    2010-01-01

    Serum lipid profile has now become almost a routine test. It is usually done in fasting state due to certain limitations in non-fasting serum sample. In the recent past efforts have been made to simplify blood sampling by replacing fasting lipid profile with non-fasting lipid profile. However, fasting specimen is preferred if cardiovascular risk assessment is based on total cholesterol, LDL cholesterol or non-HDL cholesterol. A lot has yet to be done in this area. Till then we have to believe...

  16. Serum miR-300 as a diagnostic and prognostic biomarker in osteosarcoma.

    Science.gov (United States)

    Liu, Jian-Dong; Xin, Qun; Tao, Chun-Sheng; Sun, Pei-Feng; Xu, Peng; Wu, Bing; Qu, Liang; Li, Shu-Zhong

    2016-11-01

    In order to determine whether microRNA (miR)-300 is a diagnostic and prognostic biomarker in osteosarcoma, the miR-300 levels in serum of 114 osteosarcoma patients and 114 healthy controls were compared, followed by serum analysis of the differences between the pre-operative and post-operative sera of these osteosarcoma patients. It was observed that the concentration levels of miR-300 in the serum of osteosarcoma patients was significantly higher than those in the serum of healthy controls (P300 in the post-operative serum were significantly reduced when compared with the pre-operative serum levels (P300 levels in serum correlated significantly with clinical stage, distant metastasis and poor survival of osteosarcoma patients. Notably, serum miR-300 was an independent prognostic marker for osteosarcoma. In conclusion, our results suggested that serum miR-300 may be a potential and useful noninvasive biomarker for the early detection of osteosarcoma.

  17. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

    Directory of Open Access Journals (Sweden)

    Larsen Claus F

    2011-10-01

    Full Text Available Abstract Background Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG and biomarker profiles upon admission in trauma patients. Methods Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments, sympathoadrenal activation (adrenaline, noradrenaline, coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII. Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. Results Trauma patients had normal (86%, hypercoagulable (11% or hypocoagulable (1% TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p 10 red blood cells the initial 24 h. Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles. Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. Conclusions Trauma patients displayed

  18. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

    Science.gov (United States)

    2011-01-01

    Background Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG) and biomarker profiles upon admission in trauma patients. Methods Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry including standard coagulation tests, hematology, transfusions, Injury Severity Score (ISS) and TEG were recorded. Retrospective analysis of thawed plasma/serum for biomarkers reflecting tissue injury (histone-complexed DNA fragments), sympathoadrenal activation (adrenaline, noradrenaline), coagulation activation/inhibition and fibrinolysis (sCD40L, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer, prothrombinfragment 1+2, plasmin/α2-antiplasmin complex, thrombin/antithrombin complex, tissue factor pathway inhibitor, antithrombin, von willebrand factor, factor XIII). Comparison of patients stratified according to ISS/TEG maximum clot strength. Linear regression analysis of variables associated with clot strength. Results Trauma patients had normal (86%), hypercoagulable (11%) or hypocoagulable (1%) TEG clot strength; one had primary hyperfibrinolysis. Hypercoagulable patients had higher age, fibrinogen and platelet count (all p 10 red blood cells the initial 24 h). Patients with normal or hypercoagulable TEG clot strength had comparable biomarker profiles, but the few patients with hypocoagulable TEG clot strength and/or hyperfibrinolysis had very different biomarker profiles. Increasing ISS was associated with higher levels of catecholamines, histone-complexed DNA fragments, sCD40L, activated protein C and D-dimer and reduced levels of non-activated protein C, antithrombin, fibrinogen and factor XIII (all p 26. In patients with ISS > 26, adrenaline and sCD40L were independently negatively associated with clot strength. Conclusions Trauma patients displayed different

  19. Intestinal fibrosis in Crohn's disease: role of microRNAs as fibrogenic modulators, serum biomarkers, and therapeutic targets.

    Science.gov (United States)

    Lewis, Amy; Nijhuis, Anke; Mehta, Shameer; Kumagai, Tomoko; Feakins, Roger; Lindsay, James O; Silver, Andrew

    2015-05-01

    Inflammation often precedes fibrosis and stricture formation in patients with Crohn's disease. Established medical therapies reduce inflammation, but there are currently no specific therapies to prevent fibrosis or treat established fibrosis. Our understanding of the pathogenic processes underpinning fibrogenesis is limited compared with our knowledge of the events initiating and propagating inflammation. There are several biomarkers for intestinal inflammation, but there are none that reflect the development of fibrosis. MicroRNAs (miRNAs) are regulators of cellular activities including inflammation and fibrosis and may serve as biomarkers of disease processes. Differential serum and mucosal miRNA expression profiles have been identified between patients with inflammatory bowel disease with active and inactive inflammatory disease. In contrast, studies in patients with fibrotic phenotypes are comparatively few, although specific miRNAs have defined roles in the development of fibrosis in other organ systems. Here, we discuss the most recent research on miRNA and fibrogenesis with a particular emphasis on Crohn's disease. We also anticipate the potential of miRNAs in fulfilling current unmet translational needs in this patient group by focusing on the role of miRNAs as modulators of fibrogenesis and on their potential value as serum biomarkers and therapeutic targets in the management of fibrosis.

  20. Serum atrial natriuretic peptide: a suspected biomarker of breast cancer

    Directory of Open Access Journals (Sweden)

    Maha E. Houssen

    2017-03-01

    Full Text Available Aim of the study : To assess serum levels of ANP in breast cancer female patients and its relationship to metastasis and some clinical parameters among those patients. Material and methods : One hundred breast cancer patients with and without metastasis along with 20 healthy closely matched controls, were enrolled in the present cross sectional study. Background: To assess the serum levels of atrial natriuretic peptide in breast cancer Serum levels of ANP were assessed using ELISA. Results : Mean serum levels of ANP breast cancer patients (13.9 ±10.1 ng/ml were significantly elevated compared to healthy control group (2.2 ±1.3 ng/ml (p < 0.001. The metastatic breast cancer patients showed significant elevated ANP levels (17.1 ±8.9 ng/ml compared to non-metastatic group (6.4 ±8.8 ng/ml p < 0.001. Within the metastatic group significant difference was detected between de novo metastatic, under follow-up, under hormonal control and locally advanced group (p = 0.007. Conclusions : This study showed significant elevated levels of ANP in the serum of metastatic breast cancer patients compared to non-metastatic patients. Within the metastatic group the lowest levels were detected in metastatic breast Cancer under hormonal treatment either tamoxifen or aromatase inhibitor.

  1. Protein biomarkers and microbial profiles in peri-implantitis.

    Science.gov (United States)

    Wang, Hom-Lay; Garaicoa-Pazmino, Carlos; Collins, Amy; Ong, Hwen-Sei; Chudri, Rini; Giannobile, William V

    2016-09-01

    The aim of the present investigation was to determine the profile of peri-implant crevicular fluid (PICF) biomarkers combined with microbial profiles from implants with healthy peri-implant tissues and peri-implantitis to assess real-time disease activity. Sixty-eight patients were included in this cross-sectional study. They were divided into two groups: 34 patients with at least one healthy implant (control) and 34 with at least one peri-implantitis affected implant (test). Total DNA content and qPCR analysis for periodontal bacteria obtained from subgingival plaque samples (Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) and a PICF analysis for IL-1β, VEGF, MMP-8, TIMP-2, and OPG were performed. The individual and combined diagnostic ability of each biomarker for peri-implantitis and target bacterial species were analyzed. The mean concentration of IL-1β (44.6 vs. 135.8 pg/ml; P implantitis patients. The mean expression of MMP-8 (6029.2 vs. 5943.1 pg/ml; P = 0.454) and did not reveal a meaningful difference among groups. Total bacterial DNA of selected microorganisms was associated with a threefold or greater increase in peri-implantitis although no statistical significant difference. The ability to diagnose diseased sites was enhanced by T. denticola combined with IL-1β, VEGF, and TIMP-2 PICF levels. The present data suggest that the increased levels of the selected PICF-derived biomarkers of periodontal tissue inflammation, matrix degradation/regulation, and alveolar bone turnover/resorption combined with site-specific microbial profiles may be associated with peri-implantitis and could have potential as predictors of peri-implant diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. [Application of serum protein profiling in diagnosis, prognosis and evaluation of curative effect of pancreatic adenocarcinoma].

    Science.gov (United States)

    Guo, Jing-hui; Wang, Wen-jing; Liao, Ping; Zhang, Chun-yan; Jin, Da-yong; Lou, Wen-hui; Zhang, Shun-cai

    2010-01-01

    To establish decision tree and logistic regression classification models for diagnosing pancreatic adenocarcinoma (PaCa) and for screening serum biomarkers related to evaluation of different stages and curative effects. Serum samples obtained from subjects with pancreatic adenocarcinoma (n = 58) and normal pancreas (n = 51) were applied to strong anion exchange chromatography (SAX2) chips for protein profiling by SELDI-TOF-MS to screen multiple serum biomarkers. Biomarker Wizard software and several statistical methods including algorithm of decision tree, logistic regression and ROC curves were used to construct the decision tree or logistic regression classification models. Average of 61 mass peaks were detected at the molecular range of 2000-30,000, ten decision trees with the highest cross validation rate were chosen to construct the classification models, which can differentiate PaCa from normal pancreas with a sensitivity of 83.3% and a specificity of 100%. Logistic regression was used to achieve the AUC (0.976 +/- 0.011, P < 0.001) with a sensitivity of 77.6% - 91.4% and a specificity of 92.2% - 100%. Six mass peaks were combined by logistic regression to achieve the AUC 0.897 +/- 0.054, 0.978 +/- 0.021 and 0.792 +/- 0.107 (P < 0.05) in the three groups (patients at stage I and II, stage II and III, stage III and IV). One mass peak (M/Z 4,016) was screened (P < 0.05) significantly between the preoperative and postoperative PaCa samples and the intensity decreased weeks after operation. Decision tree and logistic regression classification models of the mass peaks screened by SELDI-TOF-MS serum profiling can be used to differentiate pancreatic adenocarcinoma from normal pancreas, and is superior to CA 199. The detected mass peaks are helpful for the evaluation of curative effect and prognosis of pancreatic adenocarcinoma.

  3. Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Philip P Becker

    Full Text Available Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001. Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001. Evaluation of score model for NAFL (Score = 0 and NASH (Score = 4 had shown high rates of sensitivity (91% and specificity (83%.Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.

  4. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

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    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

  5. Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests.

    Science.gov (United States)

    Ramsey, Jordan M; Cooper, Jason D; Penninx, Brenda W J H; Bahn, Sabine

    2016-05-31

    Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value <0.05). Simulations of biomarker studies yielded up to 40% false discoveries when patient and control groups were not matched for sex and up to 41% false discoveries when premenopausal females were not matched for oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected.

  6. Serum Biomarker Identification by Mass Spectrometry in Acute Aortic Dissection

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    Yong Ren

    2017-12-01

    Full Text Available Background/Aims: Aortic dissection (AD is also known as intramural hematoma. This study aimed to screen peripheral blood biomarkers of small molecule metabolites for AD using high-performance liquid chromatography-mass spectrometry (HPLC-MS. Methods: Sera from 25 healthy subjects, 25 patients with well-established AD, and 25 patients with well-established hypertension were investigated by HPLC-MS to detect metabolites, screen differentially expressed metabolites, and analyze metabolic pathways. Results: Twenty-six and four metabolites were significantly up- and down-regulated in the hypertensive patients compared with the healthy subjects; 165 metabolites were significantly up-regulated and 109 significantly down-regulated in the AD patients compared with the hypertensive patients. Of these metabolites, 35 were up-regulated and 105 down-regulated only in AD patients. The metabolites that were differentially expressed in AD are mainly involved in tryptophan, histidine, glycerophospholipid, ether lipid, and choline metabolic pathways. As AD alters the peripheral blood metabolome, analysis of peripheral blood metabolites can be used in auxiliary diagnosis of AD. Conclusion: Eight metabolites are potential biomarkers for AD, 3 of which were differentially expressed and can be used for auxiliary diagnosis of AD and evaluation of treatment effectiveness.

  7. Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.

    Science.gov (United States)

    Krut, Jan Jessen; Zetterberg, Henrik; Blennow, Kaj; Cinque, Paola; Hagberg, Lars; Price, Richard W; Studahl, Marie; Gisslén, Magnus

    2013-02-01

    The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n = 12), Lyme neuroborreliosis (n = 13), herpes simplex virus type 1 (HSV-1) encephalitis (n = 10), HIV-associated dementia (HAD) (n = 21), AD (n = 21) and healthy controls (n = 42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.

  8. Serum MicroRNA profile in patients with colon adenomas or cancer

    OpenAIRE

    Zhang, Yajie; Li, Min; Ding, Yijiang; Fan, Zhimin; Zhang, Jinchun; ZHANG, HONGYING; Jiang, Bin; Zhu, Yong

    2017-01-01

    Background Colon cancer, one of the most common causes of cancer-related deaths, arises from adenomatous polyps. In these years, circulating microRNAs (miRNAs) have attracted increasing attention as novel biomarkers for colon cancers. The dysregulated circulating miRNAs in patients with colon adenomas has not been well-understood. Methods Here, we aimed to identify miRNA profile in the serum of patients with colon adenomas or colon cancer by using microarray. Then we validated eight different...

  9. Serum activin B concentration as predictive biomarker for ectopic pregnancy.

    Science.gov (United States)

    Dhiman, Pooja; Senthilkumar, G P; Rajendiran, Soundravally; Sivaraman, K; Soundararaghavan, S; Kulandhasamy, Maheshwari

    2016-05-01

    We evaluated the diagnostic accuracy of activin B in discriminating tubal ectopic pregnancy (tEP) from intrauterine miscarriages (IUM), and normal viable intrauterine pregnancy (IUP). We included 28 women with tEP, 31 women with IUM, and 29 normal IUP, confirmed both by clinical examination and ultrasonography. Serum activin B concentration was measured at the time of admission using the ELISA kit. The median serum activin B concentration was found to be significantly decreased in both tEP (p=0.004) and IUM (p=0.022) compared to normal IUP. When compared between tEP and IUM, activin B concentrations did not differ significantly. ROC analysis of activin B and free β-hCG demonstrated AUC of 0.722 and 0.805, respectively to discriminate tEP from viable IUP. The model including both activin B and free β-hCG improved the discriminating potential with greater AUC (0.824), and specificity (93%) than individual one. To discriminate tEP from IUM, activin B, free β-hCG and combination of both performed poorly. We conclude that serum activin B concentration is lower in tubal ectopic pregnancy, and can discriminate it from normal pregnancy with moderate accuracy. It also shows improved diagnostic potential along with free β-hCG, but cannot distinguish tEP from IUM reliably. Copyright © 2016. Published by Elsevier Inc.

  10. Serum monocyte chemoattractant protein-1 is a biomarker in patients with diabetes and periodontitis

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    Preethi Radhakrishnan

    2014-01-01

    Full Text Available Introduction: The role of serum Monocyte Chemoattractant Protein-1 (MCP-1 as a biomarker of periodontitis is well documented; however, its role in diabetic patients with periodontitis is unknown. Aim : This study was conducted to determine the presence and concentration of serum MCP-1 in diabetic patients with and without periodontitis and correlate it glycemic status with periodontitis. Materials and Methods: Adult diabetic patients were enrolled and grouped into group I, II, and III based on their glycemic status and serum MCP-1 estimated by ELISA. Linear regression and correlation tests were performed using R statistical software, Medcalc software to observe correlation between the serum MCP-1 and glycated hemoglobin level among different groups. Results: Serum samples obtained from 37 patients tested positive for MCP-1. Mean serum MCP-1 concentration was highest (482.3 pg/ml in group III, lowest (149.3 pg/ml in group I, and intermediate 398.8 pg/ml in group II. Correlation and regression analysis was done between HbA1c and serum MCP-1. A significant positive correlation (P 500 pg/ml in three subjects corresponded to HbA1c values more than 12.2% (group III. Conclusion: To our knowledge, this is the first study to document serum MCP-1 levels in diabetic patients with periodontitis. Glycemic status influences serum MCP-1, and lack of glycemic control contributes to increased serum MCP-1 levels. Serum MCP-1 may thus serve as a biomarker of inflammation and disease progression in diabetes with periodontitis.

  11. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

    Science.gov (United States)

    Daan, Nadine M P; Koster, Maria P H; de Wilde, Marlieke A; Dalmeijer, Gerdien W; Evelein, Annemieke M V; Fauser, Bart C J M; de Jager, Wilco

    2016-01-01

    To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. Cross-sectional comparison of serum biomarkers. University Medical Center Utrecht. Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30). Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100). The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.

  12. Multi-biomarker Profiling and Recurrent Hospitalizations in Heart Failure

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    Antoni Bayes-Genis

    2016-10-01

    Full Text Available Background: Despite advances in pharmacologic therapy and devices, patients with heart failure (HF continue to have significant rehospitalization rates and risk prediction remains challenging. We sought to explore the value of a multi-biomarker panel (including NT-proBNP, hs-TnT, and ST2 on top of clinical assessment for long-term prediction of recurrent hospitalizations in HF.Methods and Results: NT-proBNP, hs-TnT, and ST2 levels were measured in 891 consecutive ambulatory HF patients. The independent association between the multi-biomarker panel and recurrent hospitalizations was assessed through a multivariable negative binomial regression and expressed as incidence rates ratios. McFadden pseudoR2 and goodness-of-fit measures were also used. The total number of unplanned hospitalizations (all-cause, cardiovascular CV-, and HF-related were selected as the primary endpoints. At a mean follow-up of 4.2±2.1 years, 1623 all-cause hospitalizations in 498 patients (55.9%, 710 CV-related hospitalizations in 331 patients (37.2%, and 444 HF-related hospitalizations in 214 patients (24.1% were registered. The crude incidence of all-cause, CV-, and HF-related recurrent hospitalizations was significantly higher for patients with the multi-biomarker panel above the cut-point (hs-TnT>14 ng/L, NT-proBNP>1000 ng/L, and ST2>35 ng/mL (all P<0.001. For all-cause, CV-, and HF-related recurrent hospitalizations, the McFadden R2, Akaike information criterion, and Bayesian information criterion supported the superiority of incorporating the multi-biomarker panel into a clinical predictive model.Conclusions: A multi-biomarker approach that incorporates NT-proBNP, hs-TnT, and ST2 better identifies HF patients at risk for recurrent hospitalizations. Elucidation of new biophysiological targets for recurrent hospitalizations may identify patient profiles for focused intervention.

  13. Microfluidic Electrochemical Immunoarray for Ultrasensitive Detection of Two Cancer Biomarker Proteins in Serum

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    Chikkaveeraiah, Bhaskara V.; Mani, Vigneshwaran; Patel, Vyomesh; Gutkind, J. Silvio; Rusling, James F.

    2011-01-01

    A microfluidic electrochemical immunoassay system for multiplexed detection of protein cancer biomarkers was fabricated using a molded polydimethylsiloxane channel and routine machined parts interfaced with a pump and sample injector. Using off-line capture of analytes by heavily-enzyme-labeled 1 μm superparamagnetic particle (MP)-antibody bioconjugates and capture antibodies attached to an 8-electrode measuring chip, simultaneous detection of cancer biomarker proteins prostate specific antigen (PSA) and interleukin-6 (IL-6) in serum was achieved at sub-pg mL−1 levels. MPs were conjugated with ~90,000 antibodies and ~200,000 horseradish peroxidase (HRP) labels to provide efficient off-line capture and high sensitivity. Measuring electrodes feature a layer of 5 nm glutathione-decorated gold nanoparticles to attach antibodies that capture MP-analyte bioconjugates. Detection limits of 0.23 pg mL−1 for PSA and 0.30 pg mL−1 for IL-6 were obtained in diluted serum mixtures. PSA and IL-6 biomarkers were measured in serum of prostate cancer patients in total assay time 1.15 h and sensor array results gave excellent correlation with standard enzyme-linked immunosorbent assays (ELISA). These microfluidic immunosensors employing nanostructured surfaces and off-line analyte capture with heavily-labeled paramagnetic particles hold great promise for accurate, sensitive multiplexed detection of diagnostic cancer biomarkers. PMID:21632234

  14. Serum biomarkers in patients with relapsing eosinophilic granulomatosis with polyangiitis (Churg-Strauss.

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    Christian Dejaco

    Full Text Available Previous studies suggest a role for eotaxin-3, TARC/CCL17 and IgG4 in newly-diagnosed patients with eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss with highly active disease. The role of these biomarkers in relapsing disease is unclear.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio were determined in serum samples from a longitudinal cohort of patients with EGPA (105 visits of 25 patients. Epidemiological, clinical and laboratory data were available for all visits.At the first visit, 80% of patients were using glucocorticoids and 68% additional immunosuppressive drugs. Disease flares were seen at 18 visits. The median BVAS and BVAS/WG scores at time of relapse were 4 and 2, respectively. None of the biomarkers tested were useful to discriminate between active disease and remission. Patients treated with prednisone had lower eotaxin-3 and eosinophil levels compared to patients not taking glucocorticoids irrespective of disease activity. Use of immunosuppressive agents was not associated with biomarker levels.Serum levels of TARC/CCL17, eotaxin-3, IgG4, and IgG4/IgG ratio do not clearly differentiate active and inactive disease in established EGPA. Defining biomarkers in EGPA remains a challenge especially during times of glucocorticoid use.

  15. Screening and validation of serum protein biomarkers for early postmenopausal osteoporosis diagnosis.

    Science.gov (United States)

    Wang, Long; Hu, Ya-Qian; Zhao, Zhuo-Jie; Zhang, Hong-Yang; Gao, Bo; Lu, Wei-Guang; Xu, Xiao-Long; Lin, Xi-Sheng; Wang, Jin-Peng; Jie, Qiang; Luo, Zhuo-Jing; Yang, Liu

    2017-12-01

    Postmenopausal osteoporosis is one of the most prominent worldwide public health problems and the morbidity is increasing with the aging population. It has been demonstrated that early diagnosis and intervention delay the disease progression and improve the outcome. Therefore, searching for biomarkers that are able to identify postmenopausal women at high risk for developing osteoporosis is an effective way to improve the quality of life of patients, and alleviate social and economic burdens. In the present study, a protein array was used to identify potential biomarkers. The bone mineral densities of 10 rats were dynamically measured in an ovariectomized model by micro‑computed tomography assessment, and the early stage of osteoporosis was defined. Through the protein array‑based screening, the expression levels of six serum protein biomarkers in ovariectomized rats were observed to alter at the initiation stage of the postmenopausal osteoporosis. Fractalkine, tissue inhibitor of metalloproteinases‑1 and monocyte chemotactic protein‑1 were finally demonstrated to be increased in the serum of eight enrolled postmenopausal osteoporosis patients using ELISA assay and were correlated with the severity of progressive bone loss. These biomarkers may be explored as potential early biomarkers to readily evaluate and diagnose postmenopausal osteoporosis in the clinic.

  16. Endometrial cancer risk prediction including serum-based biomarkers: results from the EPIC cohort.

    Science.gov (United States)

    Fortner, Renée T; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H M; Weiderpass, Elisabete; Gram, Inger T; Gavrilyuk, Oxana; Quirós, J Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay-Tee; Allen, Naomi E; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-03-15

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p risk estimates. We used internal validation with bootstrapping (1000-fold) to adjust for over-fitting. Adiponectin, estrone, interleukin-1 receptor antagonist, tumor necrosis factor-alpha and triglycerides were selected into the model. After accounting for over-fitting, discrimination was improved by 2.0 percentage points when all evaluated biomarkers were included and 1.7 percentage points in the model including the selected biomarkers. Models including etiologic markers on independent pathways and genetic markers may further improve discrimination. © 2016 UICC.

  17. Upregulated Serum MiR-146b Serves as a Biomarker for Acute Ischemic Stroke

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    Zhenzhen Chen

    2018-01-01

    Full Text Available Background/Aims: Stroke is a major cerebrovascular disease threatening human health and life with high morbidity, disability and mortality. It is aimed to find effective biomarkers for the early diagnosis on stroke. Methods: The expressions of 17 previously reported stroke-associated miRNAs were measured using quantitative RT-PCR and the expressions of plasma high-sensitivity C reactive protein (hs-CRP and serum interleukin 6 (IL-6, the pro-inflammation markers in brain injury, were examined using enzyme-linked immunosorbent assay in 128 acute ischemic stroke (AIS patients and control group. Results: Serum miR-146b expression was significantly increased within 24 hours after stroke onset in patients compared with control group. In addition, the upregulation of serum miR-146b was strong positively correlated with plasma hs-CRP, infarct volume and National Institutes of Health Stroke Scale (NIHSS score, and moderate positively correlated with serum IL-6 of patients. Importantly, the combination of plasma hs-CRP and serum miR-146b gained a better sensitivity/specificity for prediction of AIS (AUC from 0.782 to 0.863. Conclusion: Our preliminary findings suggested that upregulated serum miR-146b in acute ischemic stroke might be a potential biomarker for AIS evaluation.

  18. Serum level of interleukin-17 and interleukin-35 as a biomarker for diagnosis of thyroid cancer.

    Science.gov (United States)

    Lu, Yi; Yuan, Ye

    2015-10-01

    The aim of this study was to evaluate the serum level of interleukin-17 (IL-17) and IL-35 in thyroid cancer patients and its diagnostic value as a biomarker. Sixty-one thyroid carcinoma patients were recruited from January 2012 to December 2014 in our hospital. Of the 61 included cases, 42 subjects were pathology confirmed with thyroid cancer and other 19 cases were diagnosed with thyroid adenoma. The serum level of IL-17 and IL-35 were compared between the two groups. The diagnosed sensitivity, specificity, and receiver operating characteristic curve (ROC) for serum IL-17 and IL-35 were evaluated according to Bayes theorem. The serum level of IL-17 were 16.3 ± 4.1 pg/ml and 9.4 ± 3.6 pg/ml for the thyroid cancer and thyroid adenoma patients respectively, with statistical difference (P 8239. The diagnosis sensitivity and specificity for serum IL-35 were 76.8% and 82.4% at the cutoff value of 57.6 pg/ml with the area under the ROC of 0.8722. The serum level of IL-17 and IL-35 was significantly different between thyroid cancer and thyroid adenoma patients, which could be a potential biomarker for the diagnosis of malignant thyroid tumor.

  19. Protein profiles of serum, brain regions and hypophyses of pubertal ...

    African Journals Online (AJOL)

    Abstract. The effects of dietary fumonisin B1 (FB1 ), a toxin produced mainly by Fusarium verticillioides and F. proliferatum that grow on maize worldwide, on protein profiles of serum, brain regions and hypophyses were studied in 24 male Large White weanling pigs randomly divided into four groups (n = 6). In a completely ...

  20. Laying performance, haematology and serum biochemical profile of ...

    African Journals Online (AJOL)

    The study was carried out to compare the effects of unfermented and fermented African locust bean on laying performance, haematology and serum biochemical profile of hens in a twelve week feeding trial. The unfermented African locust bean (UALB) contained seeds that were dehulled and boiled in water, without going ...

  1. Haematological profiles and serum lead levels in male fuel ...

    African Journals Online (AJOL)

    The haematological profiles and serum lead levels of male fuel station attendants in Calabar metropolis were determined. The haematological parameters assessed included haemoglobin concentration (Hb), haematocrit (HCT), total white blood cell count (WBC), differential white cell counts and platelet count. Age range of ...

  2. serum lipid profile in non-pregnant and pregnant hausa

    African Journals Online (AJOL)

    DR. AMINU

    Accepted: November, 2009. SERUM LIPID PROFILE IN NON-PREGNANT AND PREGNANT HAUSA-. FULANI WOMEN AT SECOND AND THIRD TRIMESTERS OF PREGNANCY IN. KURA LOCAL GOVERNMENT AREA, KANO STATE, NIGERIA. 1*A.I. Salisu, and 2M.K. Atiku. 1* Department of Human Physiology, Faculty ...

  3. Haematological profile and serum biochemical indices of weaned ...

    African Journals Online (AJOL)

    This study was carried out to determine the haematological profile and serum biochemical indices of rabbits fed pawpaw (Carica papaya) leaves as feed supplement to a corn – soybean mealbasal diet. The study involved thirty six (36) cross bred (New Zealand White X Chinchilla) mixed sex weaned rabbits of five - six ...

  4. Increased Free Circulating DNA Integrity Index as a Serum Biomarker in Patients with Colorectal Carcinoma.

    Science.gov (United States)

    El-Gayar, Dina; El-Abd, Nevine; Hassan, Noha; Ali, Reem

    2016-01-01

    Cell-free DNA circulating in blood is a candidate biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic non diseased cells, DNA released from necrotic cancer cells varies in size. To measure the DNA integrity index in serum and the absolute DNA concentration to assess their clinical utility as potential serum biomarkers for colorectal carcinoma (CRC) compared to CEA and CA19-9. Fifty patients with CRC, 10 with benign colonic polyps and 20 healthy sex and age matched volunteers, were investigated by real time PCR of ALU repeats (ALU q-PCR) using two sets of primers (115 and 247 bp) amplifying different lengths of DNA fragments. The DNA integrity index was calculated as the ratio of q-PCR results of ALU 247/ ALU 115bp. Serum DNA integrity was statistically significantly higher in CRC patients compared to the benign and control groups (pintegrity index is superior to the absolute DNA concentration as a potential serum biomarker for screening and diagnosis of CRC. It may also serve as an indicator for monitoring the progression of CRC patients. Combining CEA and CA19-9 with either of the genetic markers studied is better than either of them alone.

  5. Serum PCB levels and congener profiles among US construction workers

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    Altshul Larisa

    2007-08-01

    Full Text Available Abstract Background The presence of PCB in caulking (sealant material found in masonry buildings has been well-documented in several countries. A recent investigation of 24 buildings in the greater Boston area found that 8 buildings had high PCB levels in caulking materials used around window frames and in joints between masonry blocks. Workers removing caulking material have been shown to have elevated serum PCB levels. Methods This project compared serum PCB levels among male workers who installed and/or removed PCB-containing caulking material from buildings in the greater Boston area with reference serum PCB levels from 358 men from the same area. Serum PCB levels were measured in the same laboratory by liquid-liquid extraction, column chromatography clean-up and dual capillary column GC/microECD analysis. Results When the congener profiles were compared between the reference population and the construction workers, the serum levels of the more volatile, lighter PCBs (di-, tri-and tetrachloro, sum of IUPAC# 6–74 were substantially higher among the construction workers. One of the youngest workers had the lowest total serum PCB levels (sum of 57 congeners of all 6 workers, but the contribution of more volatile (less chlorinated PCB congeners (#16, 26,28,33,74,66, and 60 was markedly higher than in other 5 workers and reference men. Only this worker was working on a job that involved removing PCB caulking at the time of the blood sampling. Conclusion While the results of this pilot study are based upon small numbers (6 construction workers who handled PCB caulking, the serum PCB levels among the construction workers exceed the referents. Comparison of the congener profiles suggests that there are substantial differences between the construction workers and the general population samples. These differences, and the similarities of profiles among the construction workers strongly suggest that occupational contact with caulking material can be

  6. Immunometabolic biomarkers of inflammation in Behçet's disease: relationship with epidemiological profile, disease activity and therapeutic regimens

    Science.gov (United States)

    Pucino, V.; Vitale, A.; Talarico, R.; M. Lucherini, O.; Magnotti, F.; De Rosa, V.; Galgani, M.; Alviggi, C.; Marone, G.; Galeazzi, M.

    2016-01-01

    Summary Behcet's disease (BD) is a systemic inflammatory disease with a still unclear pathogenesis. Although several inflammatory molecules have been studied, current biomarkers are largely insensitive in BD and unable to predict disease progression and response to treatment. Our primary aim was to explore serum levels of soluble CD40 L (sCD40L), soluble intracellular adhesion molecule (sICAM‐1), monocyte chemoattractant protein‐1 (MCP‐1), myeloperoxidase (MPO), leptin, resistin, osteoprotegerin (OPG), soluble type 1 tumour necrosis factor receptor (sTNFR), interleukin (IL)−6 and serum amyloid A (SAA) serum concentration in a cohort of 27 BD patients. The secondary aim was to evaluate potential correlations between the putative circulating biomarkers, demographic profile of patients, the status of disease activity, the specific organ involvement at the time of sample collection and different therapeutic regimens. Serum concentrations of sTNFR (P = 0·008), leptin (P = 0·0011), sCD40L (P disease than HC (P = 0·0108). A correlation between sTNFR and age was also found, with higher levels in patients over 40 years than HC (P = 0·0329). Although further research is warranted to elucidate the role of circulating biomarkers, some of that may contribute to the understanding of the physiopathology processes underlying BD activity and damage as well as to provide useful tools for prognostic purposes and a personalized treatment approach. PMID:26756979

  7. Discriminating patients with early-stage pancreatic cancer or chronic pancreatitis using serum electrospray mass profiling

    Science.gov (United States)

    Hocker, James R.; Postier, Russell G.; Li, Min; Lerner, Megan R.; Lightfoot, Stan A.; Peyton, Marvin D.; Deb, Subrato J.; Baker, Candace M.; Williams, Travis L.; Hanas, Rushie Jane; Stowell, Donald E.; Lander, Theresa J.; Brackett, Daniel J.; Hanas, Jay S.

    2015-01-01

    Blood tests are needed to aid in the early detection of pancreatic ductal adenocarcinoma (PDAC), and monitoring pancreatitis development into malignancy especially in high risk patients. This study exhibits efforts and progress toward developing such blood tests, using electrospray-mass spectrometry (MS) serum profiling to distinguish patients with early-stage PDAC or pancreatitis from each other and from controls. Identification of significant serum mass peak differences between these individuals was performed using t tests and “leave one out” cross validation. Serum mass peak distributions of control individuals were distinguished from those of patients with chronic pancreatitis or early-stage PDAC with P values early-stage PDAC with a P value stages I, IIA and IIB were blindly validated from controls. Tandem MS/MS identified a cancer phenotype with elements of PDAC involved in early-stage PDAC/control discrimination. These studies indicate electrospray-MS mass profiling can detect serum changes in patients with pancreatitis or early-stage pancreatic cancer. Such technology has the potential to aid in early detection of pancreatic cancer, biomarker development, and in monitoring development of pancreatitis into PDAC. PMID:25637792

  8. Biomarker Identification and Pathway Analysis by Serum Metabolomics of Lung Cancer

    Directory of Open Access Journals (Sweden)

    Yingrong Chen

    2015-01-01

    Full Text Available Lung cancer is one of the most common causes of cancer death, for which no validated tumor biomarker is sufficiently accurate to be useful for diagnosis. Additionally, the metabolic alterations associated with the disease are unclear. In this study, we investigated the construction, interaction, and pathways of potential lung cancer biomarkers using metabolomics pathway analysis based on the Kyoto Encyclopedia of Genes and Genomes database and the Human Metabolome Database to identify the top altered pathways for analysis and visualization. We constructed a diagnostic model using potential serum biomarkers from patients with lung cancer. We assessed their specificity and sensitivity according to the area under the curve of the receiver operator characteristic (ROC curves, which could be used to distinguish patients with lung cancer from normal subjects. The pathway analysis indicated that sphingolipid metabolism was the top altered pathway in lung cancer. ROC curve analysis indicated that glycerophospho-N-arachidonoyl ethanolamine (GpAEA and sphingosine were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. Compared with the traditional lung cancer diagnostic biomarkers carcinoembryonic antigen and cytokeratin 19 fragment, GpAEA and sphingosine were as good or more appropriate for detecting lung cancer. We report our identification of potential metabolic diagnostic and prognostic biomarkers of lung cancer and clarify the metabolic alterations in lung cancer.

  9. Serum Mineral Profile in Various Reproductive Phases of Mares

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    Farah Ali1, Laeeq Akbar Lodhi*2, Zafar Iqbal Qureshi2, Ijaz Ahmad2 and Riaz Hussain1

    2013-07-01

    Full Text Available The present study was conducted to determine the trace mineral profile in fertile, subfertile and pregnant mares kept under different management conditions. For this purpose the blood samples were collected without anticoagulant from 100 field mares and 100 farm mares for serum separation. All animals were grouped according to their history and rectal examination. Serum manganese levels in pregnant mares were significantly (P<0.05 higher than all other mares. Serum iron levels showed no significant difference between the groups and within the groups. Pregnant mare in field conditions showed significantly (P<0.05 higher serum copper level than farm animals. Serum zinc levels in estrual group of mares under field conditions showed significantly (P<0.05 lower levels compared with rest of the three groups and from farm maintained groups. Serum zinc levels in estrual mares under farm condition were significantly (P<0.05 higher as compared to their counterparts under field conditions. Fertile, subfertile and pregnant mares under field conditions differed significantly (P<0.05 from one another, pregnant mares showed significantly (P<0.05 higher levels compared with rest of three groups under same condition. Pregnant mares under field conditions showed significantly (P<0.05 higher serum selenium levels when compared with the farm animals. It can be concluded that deficiency of manganese, iron, zinc, copper and selenium might be possible causes of infertility in mares.

  10. Exploration of potential biomarkers and related biological pathways for PCB exposure in maternal and cord serum: A pilot birth cohort study in Chiba, Japan.

    Science.gov (United States)

    Eguchi, Akifumi; Sakurai, Kenichi; Watanabe, Masahiro; Mori, Chisato

    2017-05-01

    Polychlorinated biphenyls (PCBs) have been associated with adverse human reproductive and fetal developmental measures or outcomes because of their endocrine-disrupting effects; however, the biological mechanisms of adverse effects of PCB exposure in humans are not currently well established. In this study, we aimed to identify the biological pathways and potential biomarkers of PCB exposure in maternal and umbilical cord serum using a hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) metabolomics platform. The median concentration of total PCBs in maternal (n=93) and cord serum (n=93) were 350 and 70pgg(-1) wet wt, respectively. PCB levels in maternal and fetal serum from the Chiba Study of Mother and Children's Health (C-MACH) cohort are comparable to those of earlier cohort studies conducted in Japan, the USA, and European countries. We used the random forest model with the metabolome profile to predict exposure levels of PCB (first quartile [Q1] and fourth quartile [Q4]) for pregnant women and fetuses. In the prediction model for classification of Q1 versus Q4 (area-under-curve [AUC]: pregnant women=0.812 and fetuses=0.919), citraconic acid level in maternal serum and ethanolamine, p-hydroxybenzoate, and purine levels in cord serum had >0.70 AUC values. These candidate biomarkers and metabolite included in composited models were related to glutathione and amino acid metabolism in maternal serum and the amino acid metabolism and ubiquinone and other terpenoid-quinone biosynthesis in cord serum (FDR PCB exposure in pregnant women and fetuses. These results showed that metabolome analysis might be useful to explore potential biomarkers and related biological pathways for PCB exposure. Thus, more detailed studies are needed to verify sensitivity of the biomarkers and clarify the biochemical changes resulting from PCB exposure. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.

    Science.gov (United States)

    Saito, Takafumi; Sugimoto, Masahiro; Okumoto, Kazuo; Haga, Hiroaki; Katsumi, Tomohiro; Mizuno, Kei; Nishina, Taketo; Sato, Sonoko; Igarashi, Kaori; Maki, Hiroko; Tomita, Masaru; Ueno, Yoshiyuki; Soga, Tomoyoshi

    2016-07-21

    To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. The serum levels of low-molecular-weight metabolites in 68 patients with HCC were quantified using capillary electrophoresis chromatography and mass spectrometry. Thirty and 38 of the patients suffered from hepatitis B virus-related HCC (HCC-B) and hepatitis C virus-related HCC (HCC-C), respectively. The main metabolites characteristic of HCC were those associated with glutathione metabolism, notably 13 γ-glutamyl peptides, which are by-products of glutathione induction. Two major profiles, i.e., concentration patterns, of metabolites were identified in HCC patients, and these were classified into two groups: an HCC-B group and an HCC-C group including some of the HCC-B cases. The receiver operating characteristic curve for the multiple logistic regression model discriminating HCC-B from HCC-C incorporating the concentrations of glutamic acid, methionine and γ-glutamyl-glycine-glycine showed a highly significant area under the curve value of 0.94 (95%CI: 0.89-1.0, P < 0.0001). The serum levels of γ-glutamyl peptides, as well as their concentration patterns, contribute to the development of potential biomarkers for virus-related HCC. The difference in metabolite profiles between HCC-B and HCC-C may reflect the respective metabolic reactions that underlie the different pathogeneses of these two types of HCC.

  12. Calibration-free concentration analysis of protein biomarkers in human serum using surface plasmon resonance.

    Science.gov (United States)

    Grover Shah, Veenita; Ray, Sandipan; Karlsson, Robert; Srivastava, Sanjeeva

    2015-11-01

    In complex biological samples such as serum, determination of specific and active concentration of target proteins, independent of a calibration curve, will be valuable in many applications. Calibration-free concentration analysis (CFCA) is a surface plasmon resonance (SPR)-based label-free approach, which calculates active concentration of proteins using their known diffusion coefficient and observed changes in binding rates at different flow rates under diffusion-limited conditions. Here, for the first time we demonstrate the application of CFCA for determining protein biomarker abundance, specifically serum amyloid A (SAA), directly in the serum samples of patients suffering from different infectious and non-infectious diseases. The assay involves preparation of appropriate reaction surfaces by immobilizing antibodies on CM5 chips via amine coupling followed by serum sample preparation and injection over activated and reference surfaces at flow-rates of 5 and 100 μL/min. The system was validated in healthy and diseased (infectious and non-infectious) serum samples by quantifying two different proteins: β2-microglobulin (β2M) and SAA. All concentration assays were performed for nearly 100 serum samples, which showed reliable quantification in unattended runs with high accuracy and sensitivity. The method could detect the serum β2M to as low as 13 ng/mL in 1000-fold serum dilution, indicating the possible utility of this approach to detect low abundance protein biomarkers in body fluids. Applying the CFCA approach, significant difference in serum abundance of SAA was identified in diseased subjects as compared to the healthy controls, which correlated well with our previous proteomic investigations. Estimation of SAA concentration for a subset of healthy and diseased sera was also performed using ELISA, and the trend was observed to be similar in both SPR assay and ELISA. The reproducibility of CFCA in various serum samples made the interpretation of assay

  13. A pilot study of serum microRNAs panel as potential biomarkers for diagnosis of nonalcoholic fatty liver disease.

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    Youwen Tan

    Full Text Available The invasive nature of liver biopsy makes the histopathological diagnosis of non-alcoholic fatty liver disease (NAFLD difficult and its diagnostic performance unsatisfactory. The present study aimed to identify a serum microRNA (miRNA expression profile that could serve as a novel diagnostic biomarker for NAFLD.Serum miRNA expression was investigated using three cohorts comprising 465 participants (healthy controls and NAFLD patients recruited between August 2010 and June 2013. miRNA expression was initially screened by Illumina sequencing using serum samples pooled from 20 patients and 20 controls. Quantitative reverse transcriptase polymerase chain reaction assay was then used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 242 and validated using another cohort (n = 183. The area under the receiver operating characteristic curve (AUC was used to evaluate diagnostic accuracy.We identified an miRNA panel (hsa-miR-122-5p, hsa-miR-1290, hsa-miR-27b-3p, and hsa-miR-192-5p with a high diagnostic accuracy for NAFLD. The satisfactory diagnostic performance of the miRNA panel remained regardless of the NAFLD activity score (NAS status. There was significant difference between the AUC values of the miRNA panel and those of ALT (AUC = 0.786, 95% CI = 0.717-0.855; P = 0.142 and FIB-4 (AUC = 0.795, 95% CI = 0.730-0.860; sensitivity = 69.9%, specificity = 83.7%.We identified a serum microRNA panel with considerable clinical value in NAFLD diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for NAFLD than ALT and FIB-4.

  14. SERUM LIPIDOMIC BIOMARKERS FROM PATIENTS WITH PROSTATE PATHOLOGY, IDENTIFIED BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED WITH MASS SPECTROMETRY

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    Gligor Andrei Lazar

    2016-11-01

    Full Text Available Introduction: Lipidomics can offer an instant picture of the lipophilic metabolites from tissues and biofluids and can indicate the evolution of different pathologies, such as hyperplasia or different types of cancers. Related to these pathologies, Prostate Serum Antigen (PSA, proved to have a low grade prediction for an accurate diagnosis. Meanwhile, untargeted or targeted metabolomics became a useful advanced technology to discover new biomarkers for a better diagnosis. Aims: To  realize an adequate procedure based on liquid chromatography coupled with mass spectrometry (HPLC-MS to determine the profile of lipids from blood serum, followed by adequate biostatistics. Materials and Methods: Blood samples, obtained from healthy men and patients with prostate benign hyperplasia,  post-biopsy cancer and post-surgery cancer were processed for lipid extraction and subjected to HPLC–ESI(+QTOF-MS measurements, followed by the multivariate analysis (PCA and Cluster Analysis with Unscrambler 10.1 software. TofControl 3.2 and Data Analysis 4.2 software (BrukerDaltonics were used for the control of the instrument and data processing. Results: The molecules responsible for such discriminations were identified to be mainly represented by lyso-phospatidylcholines. By Cluster Analysis, the dendograms showed good statistical clustering of samples, especially for cancer patients agains controls and less clustered for hyperplasia. Conclusion: One can consider that molecules belonging to phospholipid family and diacyl /triacylglycerides or ceramides or carnitines can be considered potential biomarkers for hyperplasia and prostate cancer.

  15. Thrombelastography and biomarker profiles in acute coagulopathy of trauma: a prospective study

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Sørensen, Anne Marie; Larsen, Claus F

    2011-01-01

    Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG) and biomarker profiles upon admission in trauma patients.......Severe injury induces an acute coagulopathy associated with increased mortality. This study compared the Thrombelastography (TEG) and biomarker profiles upon admission in trauma patients....

  16. Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men

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    Zhe Zhang

    2017-01-01

    Full Text Available Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22 and healthy controls (n = 31 were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS. Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including d-glutamine and d-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility.

  17. Serum microRNA-135a-5p as an auxiliary diagnostic biomarker for colorectal cancer.

    Science.gov (United States)

    Wang, Qinjun; Zhang, Hongchun; Shen, Xianjuan; Ju, Shaoqing

    2017-01-01

    Objective The purpose of this study was to explore serum miR-135a-5p expression in colorectal cancer and examine the potential usefulness of this molecule as a biomarker for diagnosis in colorectal cancer. Methods Serum samples were collected from 60 patients with primary colorectal cancer, 40 patients with colorectal polyps and 50 healthy controls. Serum miR-135a-5p expression levels were detected by reverse transcription quantitative real-time quantitative polymerase chain reaction. Serum carcinoembryonic antigen and carbohydrate antigen 199 concentrations were detected by MODULAR ANALYTICS E170. Results The relative expression level of serum miR-135a-5p in colorectal cancer patients, colorectal polyps patients and healthy controls was 2.451 (1.107, 4.413), 0.946 (0.401, 1.942) and 0.949 (0.194, 1.415), respectively, indicating that it was significantly higher in colorectal cancer patients than that in the other two groups ( U = 351.0, 313.0, both P colorectal cancer patients. Compared with colorectal polyps group, AUCROC of serum miR-135a-5p in colorectal cancer group was 0.832 with 95% CI 0.73-0.93; compared with healthy control group, AUCROC was 0.875 with 95% CI 0.80-0.95. Conclusion Serum miR-135a-5p expression in colorectal cancer patients was higher than that in patients with colorectal polyps and healthy controls, suggesting that serum miR-135a-5p may prove to be an important biomarker for auxiliary diagnosis of colorectal cancer.

  18. Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia.

    Science.gov (United States)

    Buhimschi, Irina A; Zhao, Guomao; Funai, Edmund F; Harris, Nathan; Sasson, Isaac E; Bernstein, Ira M; Saade, George R; Buhimschi, Catalin S

    2008-11-01

    The cause of preeclampsia remains unknown and the diagnosis can be uncertain. We used proteomic-based analysis of urine to improve disease classification and extend the pathophysiologic understanding of preeclampsia. Urine samples from 284 women were analyzed by surface-enhanced laser desorption/ionization. In the exploratory phase, 59 samples were used to extract the proteomic fingerprint characteristic of severe preeclampsia requiring mandated delivery and to develop a diagnostic algorithm. In the challenge phase, we sought to prospectively validate the algorithm in 225 women screened for a variety of high- and low-risk conditions, including preeclampsia. Of these, 19 women were followed longitudinally throughout pregnancy. The presence of biomarkers was interpreted relative to clinical classification, need for delivery, and other urine laboratory measures (ratios of protein to creatinine and soluble fms-like tyrosine kinase-1 to placental growth factor). In the translational phase, biomarker identification by tandem mass spectrometry and validation experiments in urine, serum, and placenta were used to identify, quantify, and localize the biomarkers or related proteins. We report that women with preeclampsia appear to present a unique urine proteomic fingerprint that predicts preeclampsia in need of mandated delivery with highest accuracy. This characteristic proteomic profile also has the ability to distinguish preeclampsia from other hypertensive or proteinuric disorders in pregnancy. Pregnant women followed longitudinally who developed preeclampsia displayed abnormal urinary profiles more than 10 weeks before clinical manifestation. Tandem mass spectrometry and de novo sequencing identified the biomarkers as nonrandom cleavage products of SERPINA1 and albumin. Of these, the 21 amino acid C-terminus fragment of SERPINA1 was highly associated with severe forms of preeclampsia requiring early delivery. In preeclampsia, increased and aberrant SERPINA1

  19. Biomarkers intersect with the exposome.

    Science.gov (United States)

    Rappaport, Stephen M

    2012-09-01

    The exposome concept promotes use of omic tools for discovering biomarkers of exposure and biomarkers of disease in studies of diseased and healthy populations. A two-stage scheme is presented for profiling omic features in serum to discover molecular biomarkers and then for applying these biomarkers in follow-up studies. The initial component, referred to as an exposome-wide-association study (EWAS), employs metabolomics and proteomics to interrogate the serum exposome and, ultimately, to identify, validate and differentiate biomarkers of exposure and biomarkers of disease. Follow-up studies employ knowledge-driven designs to explore disease causality, prevention, diagnosis, prognosis and treatment.

  20. Validation processes of protein biomarkers in serum--a cross platform comparison.

    Science.gov (United States)

    Köhler, Katja; Seitz, Harald

    2012-01-01

    Due to insufficient biomarker validation and poor performances in diagnostic assays, the candidate biomarker verification process has to be improved. Multi-analyte immunoassays are the tool of choice for the identification and detailed validation of protein biomarkers in serum. The process of identification and validation of serum biomarkers, as well as their implementation in diagnostic routine requires an application of independent immunoassay platforms with the possibility of high-throughput. This review will focus on three main multi-analyte immunoassay platforms: planar microarrays, multiplex bead systems and, array-based surface plasmon resonance (SPR) chips. Recent developments of each platform will be discussed for application in clinical proteomics, principles, detection methods, and performance strength. The requirements for specific surface functionalization of assay platforms are continuously increasing. The reasons for this increase is the demand for highly sensitive assays, as well as the reduction of non-specific adsorption from complex samples, and with it high signal-to-noise-ratios. To achieve this, different support materials were adapted to the immobilized biomarker/ligand, allowing a high binding capacity and immobilization efficiency. In the case of immunoassays, the immobilized ligands are proteins, antibodies or peptides, which exhibit a diversity of chemical properties (acidic/alkaline; hydrophobic/hydrophilic; secondary or tertiary structure/linear). Consequently it is more challenging to develop immobilization strategies necessary to ensure a homogenous covered surface and reliable assay in comparison to DNA immobilization. New developments concerning material support for each platform are discussed especially with regard to increase the immobilization efficiency and reducing the non-specific adsorption from complex samples like serum and cell lysates.

  1. Relationship between weight loss in obese knee osteoarthritis patients and serum biomarkers of cartilage breakdown

    DEFF Research Database (Denmark)

    Bartels, E M; Henrotin, Y; Bliddal, H

    2017-01-01

    OBJECTIVE: To explore effects of weight loss and maintenance on serum cartilage biomarkers denaturation neoepitope for Collagen2 (Coll2-1) and Fibulin3 fragment (Fib3-2), as well as correlations between Coll2-1 and Fib3-2 and symptomatic improvement, in a knee osteoarthritis (KOA) population...... patients was not associated with decrease in markers of cartilage breakdown Coll2-1 or Fib3-2, even with indications of a slightly negative effect....

  2. Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD

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    Pinto-Plata Victor

    2012-08-01

    Full Text Available Abstract Background The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. Methods We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and16, tumor necrosis factor alpha (TNF α [inflammatory panel], vascular endothelial growth factor (VEGF, and matrix metalloproteinase 9 (MMP-9 [injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18 and monocyte chemotactic protein 1 (MCP-1/CCL2 [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID using a novel visualization method [ObServed Clinical Association Results (OSCAR plot]. Results Levels of the inflammatory markers IL-6, TNF α were higher and those of injury and repair lower (p  Conclusions In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.

  3. Systemic disease-induced salivary biomarker profiles in mouse models of melanoma and non-small cell lung cancer.

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    Kai Gao

    2009-06-01

    Full Text Available Saliva (oral fluids is an emerging biofluid poised for detection of clinical diseases. Although the rationale for oral diseases applications (e.g. oral cancer is intuitive, the rationale and relationship between systemic diseases and saliva biomarkers are unclear.In this study, we used mouse models of melanoma and non-small cell lung cancer and compared the transcriptome biomarker profiles of tumor-bearing mice to those of control mice. Microarray analysis showed that salivary transcriptomes were significantly altered in tumor-bearing mice vs. controls. Significant overlapping among transcriptomes of mouse tumors, serum, salivary glands and saliva suggests that salivary biomarkers have multiple origins. Furthermore, we identified that the expression of two groups of significantly altered transcription factors (TFs Runx1, Mlxipl, Trim30 and Egr1, Tbx1, Nr1d1 in salivary gland tissue of melanoma-bearing mice can potentially be responsible for 82.6% of the up-regulated gene expression and 62.5% of the down-regulated gene expression, respectively, in the saliva of melanoma-bearing mice. We also showed that the ectopic production of nerve growth factor (NGF in the melanoma tumor tissue as a tumor-released mediator can induce expression of the TF Egr-1 in the salivary gland.Taken together, our data support the conclusion that upon systemic disease development, significant changes can occur in the salivary biomarker profile. Although the origins of the disease-induced salivary biomarkers may be both systemic and local, stimulation of salivary gland by mediators released from remote tumors plays an important role in regulating the salivary surrogate biomarker profiles.

  4. Serum Cytokine Profile in a Patient Diagnosed with Dysferlinopathy

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    Svetlana F. Khaiboullina

    2017-01-01

    Full Text Available Limb-girdle muscular dystrophy type 2 (LGMD2B is a mild form of dysferlinopathy, characterized by limb weakness and wasting. It is an autosomal recessive disease, with currently 140 mutations in the LGMD2B gene identified. Lack of functional dysferlin inhibits muscle fiber regeneration in voluntary muscles, the main pathological finding in LGMD2B patients. However, the immune system has been suggested to contribute to muscle cell death and tissue regeneration. Serum levels of 27 cytokines were evaluated in a dysferlinopathy patient. Levels of 8 cytokines differed in patient serum compared to controls. Five cytokines (IL-10, IL-17, CCL2, CXCL10, and G-CSF were higher while 3 were lower in the patient than in controls (IL-2, IL-8, and CCL11. Together, these data on serum cytokine profile of this dysferlinopathy patient suggest immune response activation, which could explain leukocyte infiltration in the muscle tissue.

  5. Relationship between serum biomarkers of cartilage and bone metabolism and joint injury in young Thoroughbred racehorses in training.

    Science.gov (United States)

    Jackson, Brendan F; Reed, Suzanne R; Price, Joanna S; Verheyen, Kristien L P

    2015-08-01

    To compare serum concentrations of biomarkers of cartilage and bone metabolism between racehorses with a carpal or metacarpophalangeal or metatarsophalangeal (ie, fetlock) joint injury and matched uninjured control horses, determine changes in biomarker concentrations following joint injury, and establish the biomarkers' diagnostic test performance. 50 Thoroughbred racehorses with a carpal or fetlock joint injury and 50 matched uninjured horses (control horses). Serum concentrations of 2 cartilage synthesis biomarkers (carboxy-terminal propeptide of type II collagen [CPII] and chondroitin sulfate epitope 846 [CS846]), 2 cartilage degradation biomarkers (neoepitope generated by collagenase cleavage of type II collagen [C2C] and cross-linked carboxy-terminal telopeptide fragments of type II collagen [CTX-II]), and serum activity of a bone formation marker (bone-specific alkaline phosphatase [BAP]) were measured around the time of injury diagnosis and monthly thereafter for as long as possible. Injured horses as a group and horses specifically with fetlock joint injuries had significantly lower serum CPII concentrations and significantly higher serum BAP activities than matched control horses. Concentrations of CTX-II were decreased between 2 and 4 months following joint injury. Measurement of CPII concentration at baseline could distinguish between injured horses and control horses with a sensitivity of 82% and specificity of 50%. Although significant differences in specific biomarker concentrations between horses with carpal and fetlock joint injuries and matched control horses were identified, there was no convincing evidence of the suitability of these biomarkers as diagnostic or prognostic tools in a clinical setting.

  6. Cord Serum Lipid Profile of Infants of Diabetic Mothers

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    Jasim Almusawi

    2015-12-01

    Full Text Available Background: Infants of diabetic mothers (IDM is a critical issue in pediatrics, which is regarded as a major risk factor for birth trauma, respiratory distress syndrome (RDS, birth asphyxia, transient tachypnea of the newborn (TTN and jaundice. IDM is also a risk factor for microvascular (e.g., ocular and renal complications and macrovascular complications (e.g., cerebrovascular accident, atherosclerosis and cardiovascular complications. Lipids are a heterogeneous group of hydrophobic organic molecules which can be extracted from tissues using non-polar solvents. Lipids, due to their hydrophobic property, are mainly found in membranes enclosing various cell organelles. Diabetes mellitus management with insulin (nowadays also with oral hypoglycemic medications has improved the outcomes of gestational diabetes mellitus (GDM (most infants born to diabetic mother are large for gestational age. The neonatal mortality rate in IDM is over five times higher than that of infants of non-diabetic mothers. In this study, therefore, we aimed to assess the effect of maternal diabetes on cord serum lipid profile. Methods: This prospective (case-control study was carried out on 60 infants born in Al-Zahra teaching hospital during February 2014–October 2014. The study group consisted of 30 randomly chosen IDM, and the control group comprised 30 infants who were born to healthy mothers. Results: The results of this study demonstrated that there are significant differences between IDM and infants of healthy mothers regarding lipid profile and birth weight. Conclusion: This study confirms that cord serum lipid profile (serum cholesterol, serum triglycerides and low-density lipoprotein is higher at birth in IDM. Moreover, this study shows a significant association between lipid profile and body weight.

  7. Serum nutritional biomarkers and their associations with sleep among US adults in recent national surveys.

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    May A Beydoun

    Full Text Available The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear.Cross-sectional data from the National Health and Nutrition Examination Surveys (NHANES 2005-2006 were used. We selected 2,459 adults aged 20-85, with complete data on key variables. Five sleep measures were constructed as primary outcomes: (A Sleep duration; (B Sleep disorder; (C Three factors obtained from factor analysis of 15 items and labeled as "Poor sleep-related daytime dysfunction" (Factor 1, "Sleepiness" (Factor 2 and "Sleep disturbance" (Factor 3. Main exposures were serum concentrations of key nutrients, namely retinol, retinyl esters, carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein+zeaxanthin, lycopene, folate, vitamin B-12, total homocysteine (tHcy, vitamin C, 25-hydroxyvitamin D (25(OHD and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models.Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OHD and sleepiness (as well as insomnia, and between folate and sleep disturbance. Serum total carotenoids concentration was linked to higher odds of short sleep duration (i.e. 5-6 h per night compared to normal sleep duration (7-8 h per night.A few of the selected serum nutritional biomarkers were associated with sleep quantity and quality. Longitudinal studies are needed to ascertain temporality and assess putative causal relationships.

  8. Protective Effect of Cornus mas Fruits Extract on Serum Biomarkers in CCl4-Induced Hepatotoxicity in Male Rats.

    Science.gov (United States)

    Alavian, Seyed Moayed; Banihabib, Nafiseh; Es Haghi, Masoud; Panahi, Farid

    2014-04-01

    Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties. The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats. Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity. Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders.

  9. Relationship of examination stress to serum lipid profile.

    Science.gov (United States)

    Bijlani, R L; Sud, S; Gandhi, B M; Tandon, B N

    1986-01-01

    Although mental stress as well as hypercholesterolaemia have been individually linked with atherosclerosis, the relationship between mental stress and hypercholesterolaemia is poorly understood. Serum lipid profile was studied in eight male medical student volunteers before, near and after examinations. Identical observations were also made on seven well-matched control volunteers. As compared to pre-exam levels, total serum cholesterol (T-C) increased significantly (P less than 0.05) near exams, and so did low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). The HDL-C/T-C and HDL-C/LDL-C ratios remained essentially constant throughout the study. Control subjects did not show any significant change in serum lipid profile. Further serial measurement in five of the subjects revealed that examination-related changes were transient. Moreover, a second examination after about 40 days did not evoke any change in the lipid profile. The response to examination stress may be related to the enhanced utilisation of cholesterol in the adrenal cortex for steroidogenesis.

  10. Usefulness of gel filtration fraction as potential biomarker for neurocysticercosis in serum: towards a new diagnostic tool.

    Science.gov (United States)

    Nunes, D S; Gonzaga, H T; Ribeiro, V S; Cunha-Júnior, J P; Costa-Cruz, J M

    2017-04-01

    There is an increasing interest in improving neurocysticercosis (NCC) diagnosis through the search of new and alternative antigenic sources, as those obtained from heterologous antigens. The aim of this study was to obtain potential biomarkers for NCC diagnosis after gel filtration chromatography [gel filtration fraction (GFF)] from the total saline extract (SE) from Taenia saginata metacestodes, followed by protein identification and application in immunodiagnostic. SE and GFF proteic profiles were characterized in gel electrophoresis, and diagnostic performance was verified by testing 160 serum samples through enzyme-linked immunosorbent assay and immunoblotting. Sensitivity (Se), specificity (Sp) and other diagnostic parameters were calculated. Polypeptides of interest in the diagnosis of human NCC present at GFF were analysed by mass spectrometry (MS) and B-cell epitopes were predicted. GFF had the best diagnostic parameters: Se 93·3%; Sp 93%; AUC 0·990; LR+ = 13·42 and LR- = 0·07, and proved to be useful reacting with serum samples in immunoblotting. Proteic profile ranged from 64 to 68 kDa and enolase and calcium binding protein calreticulin precursor were identified after MS. The enolase and calcium-binding protein calreticulin precursor showed 18 and 10 predicted B-cell epitopes, respectively. In conclusion we identified important markers in the GFF with high efficiency to diagnose NCC.

  11. Discovery of serum biomarkers predicting development of a subsequent depressive episode in social anxiety disorder.

    Science.gov (United States)

    Gottschalk, M G; Cooper, J D; Chan, M K; Bot, M; Penninx, B W J H; Bahn, S

    2015-08-01

    Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a 2-year follow-up period. One hundred sixty-five multiplexed immunoassay analytes were investigated in blood serum of 143 SAD patients without co-morbid depressive disorders, recruited within the Netherlands Study of Depression and Anxiety (NESDA). Predictive performance of identified biomarkers, clinical variables and self-report inventories was assessed using receiver operating characteristics curves (ROC) and represented by the area under the ROC curve (AUC). Stepwise logistic regression resulted in the selection of four serum analytes (AXL receptor tyrosine kinase, vascular cell adhesion molecule 1, vitronectin, collagen IV) and four additional variables (Inventory of Depressive Symptomatology, Beck Anxiety Inventory somatic subscale, depressive disorder lifetime diagnosis, BMI) as optimal set of patient parameters. When combined, an AUC of 0.86 was achieved for the identification of SAD individuals who later developed a depressive disorder. Throughout our analyses, biomarkers yielded superior discriminative performance compared to clinical variables and self-report inventories alone. We report the discovery of a serum marker panel with good predictive performance to identify SAD individuals prone to develop subsequent depressive episodes in a naturalistic cohort design. Furthermore, we emphasise the importance to combine biological markers, clinical variables and self-report inventories for disease course predictions in psychiatry. Following replication in independent cohorts, validated biomarkers could help to identify SAD patients at risk of developing a depressive disorder, thus facilitating early intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Potential serum and urine biomarkers in patients with lupus nephritis and the unsolved problems

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    Hsieh SC

    2016-09-01

    Full Text Available Song-Chou Hsieh,1 Chang-Youh Tsai,2 Chia-Li Yu3 1Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, 2Section of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, 3Department of Internal Medicine, Institute of Molecular Medicine, National Taiwan University College of Medicine, Taipei, Taiwan Abstract: Lupus nephritis (LN is one of the most frequent and serious complications in the patients with systemic lupus erythematosus. Autoimmune-mediated inflammation in both renal glomerular and tubulointerstitial tissues is the major pathological finding of LN. In clinical practice, the elevated anti-dsDNA antibody titer concomitant with reduced complement C3 and C4 levels has become the predictive and disease-activity surrogate biomarkers in LN. However, more and more evidences suggest that autoantibodies other than anti-dsDNA antibodies, such as anti-nucleosome, anti-C1q, anti-C3b, anti-cardiolipin, anti-endothelial cell, anti-ribonuclear proteins, and anti-glomerular matrix (anti-actinin antibodies, may also involve in LN. Researchers have demonstrated that the circulating preformed and in situ-formed immune complexes as well as the direct cytotoxic effects by those cross-reactive autoantibodies mediated kidney damage. On the other hand, many efforts had been made to find useful urine biomarkers for LN activity via measurement of immune-related mediators, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomic signature, and assessment of mRNA and exosomal-derived microRNA from urine sediment cell. Our group had also devoted to this field with some novel findings. In this review, we briefly discuss the possible mechanisms of LN and try to figure out the potential serum and urine biomarkers in LN. Finally, some of the unsolved problems in this field are discussed. Keywords: anti-dsDNA antibodies, serum biomarkers, urine biomarkers, THP

  13. Relationship between exposure to industrial noise and serum lipid profile.

    Science.gov (United States)

    Mehrdad, Ramin; Bahabad, Afshin Malek; Moghaddam, Azadeh Nahan

    2011-01-01

    Aim of our study was to investigate the effects of exposure to industrial noise on serum lipid profile among workers who are exposed to noise at work. In a historical cohort study, we recruited 154 and 146 male workers as high and low level noise exposure groups respectively. We defined workers with at least one year exposure to noise level more than 90 dB as high exposure group, and those with exposure to less than 80 dB as low exposure group. Afterwards, in the fasting blood specimens of participants we measured serum Triglyceride (TG), total Cholesterol (TC), high and low density lipoprotein (HDL and LDL). Mean of TG, TC, HDL and LDL for low exposure group were 148, 189, 38 and 103 mg/dl and for high exposure group were 237, 189, 37 and 104 mg/dl respectively. Mean serum TG between two groups was different. Even after adjustment for age, BMI, smoking and work hours per week, serum TG among high exposure group was 89 mg/dl higher than low exposure group and this difference was statistically significant (P = 0.00). There was no significant difference between two groups in TC, LDL and HDL levels. This study did not find a statistically significant relationship between exposure to noise and serum TC, LDL and HDL, but TG in two groups was different and this difference was statistically significant.

  14. Relationship Between Exposure to Industrial Noise and Serum Lipid Profile

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    Ramin Mehrdad

    2011-11-01

    Full Text Available Aim of our study was to investigate the effects of exposure to industrial noise on serum lipid profile among workers who are exposed to noise at work. In a historical cohort study, we recruited 154 and 146 male workers as high and low level noise exposure groups respectively. We defined workers with at least one year exposure to noise level more than 90 dB as high exposure group, and those with exposure to less than 80 dB as low exposure group. Afterwards, in the fasting blood specimens of participants we measured serum Triglyceride (TG, total Cholesterol (TC, high and low density lipoprotein (HDL and LDL. Mean of TG, TC, HDL and LDL for low exposure group were 148, 189, 38 and 103 mg/dl and for high exposure group were 237, 189, 37 and 104 mg/dl respectively. Mean serum TG between two groups was different. Even after adjustment for age, BMI, smoking and work hours per week, serum TG among high exposure group was 89 mg/dl higher than low exposure group and this difference was statistically significant (P=0.00. There was no significant difference between two groups in TC, LDL and HDL levels. This study did not find a statistically significant relationship between exposure to noise and serum TC, LDL and HDL, but TG in two groups was different and this difference was statistically significant.

  15. Serum AFU, 5'-NT and AFP as Biomarkers for Primary Hepatocellular Carcinoma Diagnosis.

    Science.gov (United States)

    Junna, Zhu; Gongde, Chen; Jinying, Xu; Xiu, Zhou

    2017-01-01

    To evaluate the clinical value of serum α-L-fucosidase (AFU), 5'-nucleotidase (5'-NT) and alpha fetoprotein (AFP) as biomarkers for primary hepatocellular carcinoma (PHC) diagnosis. Thirty six primary hepatocellular carcinoma (PHC) patients and 36 healthy controls were recruited in this study from February 2014 to January 2016 in the Second People's Hospital of Tianjin. The serum level of AFU, 5'-NT and AFP were examined and compared between the two groups. The diagnostic sensitivity, specificity area under the receiver operating characteristic (ROC) curve were calculated by STATA11.0 software. The serum level of AFU, 5'-NT, AFP were 30.87±10.43(U/L), 5.58±3.89(U/L), 233.60±226.60 (μg/L) respectively for primary hepatocellular carcinoma group and 19.96±6.73 (U/L), 1.87±0.84 (U/L), 16.64±14.17 (μg/L) for healthy control groups. The serum level of AFU, 5'-NT and AFP in primary hepatocellular carcinoma group were significant higher than those of healthy control group (PAFP respectively. The AUC under the ROC curve were 0.80 (0.69-0.90), 0.80 (0.69-0.91) and 0.87 (0.780-0.96) for serum AFU, 5'-NT and AFP respectively. Positive correlation between AFU and 5'-NT (rpearson=0.63, PAFP (rpearson=0.49, PAFP(rpearson=0.44, PAFP were higher in PHC patients than those of healthy controls. The difference between PHC patients and healthy controls made serum AFU, 5'-NT and AFP potential biomarker for PHC diagnosis.

  16. Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson’s Disease and Related Dementia

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    Mei-Xue Dong

    2017-01-01

    Full Text Available Objective. This study aim to determine changes of serum butyrylcholinesterase (BChE activity in PD patients and related dementia. Patients and Methods. Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia. Results. Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson’s Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L. Conclusions. Serum BChE activity can be regarded as a biomarker for PD and related dementia.

  17. Evaluation of Serum Biomarkers for Patients at Increased Risk of Stroke

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    Pelisek Jaroslav

    2012-01-01

    Full Text Available Early recognition of vulnerable patients is an important issue for stroke prevention. In our study, a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors. Study subjects (=110 were divided into four groups: asymptomatic patients with stable (=25 and unstable (=36 plaques and symptomatic patients with stable (=13 and unstable (=36 plaques. Serum levels of MMP-1, -2, -3, -7, -8, -9, TIMP-1, -2, TNF-α, IL-1b, and IL-6, -8, -10, -12 were measured. Multi-score analysis was performed using multiple receiver operating characteristics (ROC and determination of appropriate cutoff values. Significant differences between the groups were observed for MMP-1, -7, -9 and TIMP-1 in serum of the study subjects (<0.05. Multiple biomarker analysis led to a significant increase in the AUC (area under curve. In case of plaque instability, positive predictive value (PPV for up to 86.4% could be correctly associated with vulnerable plaques. Thus, multiscore analysis might be preferable than the use of single biomarkers.

  18. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3 in colon cancer serum and tumours: a biomarker study

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    Olsen Jesper

    2005-01-01

    Full Text Available Abstract Background Molecular markers for localized colon tumours and for prognosis following therapy are needed. Proteomics research is currently producing numerous biomarker studies with clinical potential. We investigate the protein composition of plasma and of tumour extracts with the aim of identifying biomarkers for colon cancer. Methods By Surface Enhanced Laser Desorption/Ionisation – Time Of Flight / Mass spectrometry (SELDI-TOF/MS we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue. By size exclusion chromatography, we investigate the binding of HNP 1-3 to high mass plasma proteins. By microflow we investigate the effect of HNP 1-3 on mammalian cells. Results Human Neutrophil Peptides -1, -2 and -3 (HNP 1-3, also known as alfa-defensin-1, -2 and -3, are present in elevated concentrations in serum from colon cancer patients and in protein extracts from colon tumours. A fraction of HNP 1-3 in serum is bound to unidentified high mass plasma proteins. HNP 1-3 purified from colon tumours are lethal to mammalian cells. Conclusions HNP 1-3 may serve as blood markers for colon cancer in combination with other diagnostic tools. We propose that HNP 1-3 are carried into the bloodstream by attaching to high mass plasma proteins in the tumour microenvironment. We discuss the effect of HNP 1-3 on tumour progression.

  19. Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum

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    Higgins LeeAnn

    2010-06-01

    Full Text Available Abstract Background Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®. Results Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. Conclusions This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.

  20. Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.

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    Nadine M P Daan

    Full Text Available To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.Cross-sectional comparison of serum biomarkers.University Medical Center Utrecht.Hyperandrogenic PCOS women (HA-PCOS, n = 34, normoandrogenic PCOS women (NA-PCOS, n = 34, non-PCOS reference population (n = 32, PCOS offspring (n = 14, age 6-8 years, and a paedriatic reference population (n = 30.Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1, growth factors (PIGF, VEGF, sVEGF-R1, soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106, and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S. Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100.The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219 and adiponectin (R2 = 0.182 showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001, DPP-IV (P = 0.005, and adiponectin (P < 0.001. Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001 and S100A8 (P < 0.001 concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers

  1. Hepatocyte-derived microRNAs as sensitive serum biomarkers of hepatocellular injury in Labrador retrievers.

    Science.gov (United States)

    Dirksen, K; Verzijl, T; van den Ingh, T S G A M; Vernooij, J C M; van der Laan, L J W; Burgener, I A; Spee, B; Fieten, H

    2016-05-01

    Common parenchymal liver diseases in dogs include reactive hepatopathies and primary hepatitis (acute or chronic). In chronic hepatitis, there is usually a long subclinical phase. Specific clinical signs become overt only when liver damage is severe and in this phase, treatment is usually less effective. Limited data are available regarding the sensitivity of liver enzyme activity or biomarkers for early detection of subclinical hepatitis. Hepatocyte-derived microRNAs (HDmiRs) were recently identified as promising biomarkers for hepatocellular injury in multiple species. Here, the potential of the HDmiRs miR-122 and miR-148a as sensitive diagnostic biomarkers for hepatocellular injury in Labrador retrievers was investigated. Samples from 66 Labrador retrievers with histologically normal livers, high hepatic copper, and with various forms of liver injury were evaluated for serum alanine aminotransferase (ALT) activity and microRNA values. Median values of HDmiR-122 were 34.6 times higher in dogs with liver injury and high ALT than in normal dogs (95% confidence intervals [CI], 13-95; P dogs with liver injury and normal ALT (4.2 times; 95% CI, 2-12; P dogs with high hepatic copper concentrations and unremarkable histopathology (2.9 times; 95% CI, 1.1-8.0; P Labrador retrievers (P Labrador retrievers and is a promising new biomarker that may be used for early detection of subclinical hepatitis in dogs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Profiling of microRNAs in tumor interstitial fluid of breast tumors – a novel resource to identify biomarkers for prognostic classification and detection of cancer

    DEFF Research Database (Denmark)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel

    2017-01-01

    and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer......, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266...

  3. Evaluation of serum biochemical profile of breast cancer patients

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    Chauhan P

    2016-07-01

    Full Text Available Breast cancer is the most common cancer worldwide. The incidence and mortality rate is increasing in developing countries as compare to developed countries. The aim of this study was to evaluate the effect of different courses of chemotherapy treatment on serum biochemical profile of breast cancer patients. In the present study, two hundred breast cancer patients were selected to study variations in serum biochemical level of breast cancer patients. The mean values of blood urea nitrogen, creatinine, uric acid, aspartate aminotransferase (SGOT, alanine aminotransferase (SGPT and alkaline phosphatase was found to be 32.58±19.7mg/dl, 1.05±0.59mg/dl, 8.6±1.3mg/dl, 27.3±4.02U/L, 27.9±10.24U/L and 111±2 4.04U/L before the start of chemotherapy courses. The mean values of total and direct bilirubin, total serum protein, albumin, Fasting and postprandial glucose level was 0.30±1.3mg/dl, 0.13±0.11mg/dl, 8.11±0.5g/dl, 3.5±0. 07g/dl, 96±25 mg/dl and 110±25mg/dl before the star t of chemotherapy treatment. The level of serum blood urea nitrogen, uric acid, alkaline phosphatase, bilirubin and post-prandial glucose level was found to be more than normal reference range; while the level of creatinine, aspartate aminotransferase (AST or SGOT, alanine aminotransferase (ALT or SGPT, total serum protein, albumin and fasting blood glucose level was reported to be within normal reference range during the different courses of chemotherapy. In conclusion, present results suggest serum biochemical parameters as an important diagnostic tool in the disease monitoring and metastasis.

  4. Lessons to be learned from serum biomarkers in psoriasis and IBD - the potential role in SpA.

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    Turina, Maureen C; Landewé, Robert; Baeten, Dominique

    2017-04-01

    Early diagnosis, monitoring of disease activity, prediction of treatment response, and structural outcome remain major challenges in spondyloarthritis (SpA). Biomarkers could play a role in addressing these challenges, but in SpA there is a lack of suitable biomarkers. Areas covered: As SpA is clinically and pathophysiologically closely related to psoriasis and inflammatory bowel disease (IBD), we reviewed in literature, the value of serum biomarkers in these conditions with the aim to find potential candidates for assessing SpA. Expert commentary: Candidates of interest were antimicrobial peptides, including serum human beta defensin-2 (hBD-2) and lipocalin-2 (LCN-2), and class-1 MHC molecule beta2-microglobulin. Since these biomarkers are relevant in psoriasis and/or IBD from a pathophysiological point of view, and may play a role in the pathogenesis of SpA, we recommend further exploration of their value as biomarker in the diagnosis and prognosis of SpA.

  5. Serum biomarkers of oxidative stress in dogs with idiopathic inflammatory bowel disease.

    Science.gov (United States)

    Rubio, C P; Martínez-Subiela, S; Hernández-Ruiz, J; Tvarijonaviciute, A; Cerón, J J; Allenspach, K

    2017-03-01

    The objective of this work was to study and compare a panel of various serum biomarkers evaluating both the antioxidant response and oxidative damage in dogs with idiopathic inflammatory bowel disease (IBD). Eighteen dogs with IBD and 20 healthy dogs were enrolled in the study. Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), ferric reducing ability of the plasma (FRAP), total thiol concentrations, and paraoxonase 1 (PON1) activity were evaluated in serum to determine antioxidant response. To evaluate oxidative status, ferrous oxidation-xylenol orange (FOX), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species production (ROS) concentrations in serum were determined. Mean concentrations of all antioxidant biomarkers analyzed, with exception of FRAP, were significantly lower (P dogs with IBD than in healthy dogs. The oxidant markers studied were significantly higher (P dogs with IBD than in healthy dogs. These findings support the hypothesis that oxidative stress could play an important role in the pathogenesis of canine IBD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Analysis of IGF and IGFBP as prognostic serum biomarkers for adrenocortical carcinoma.

    Science.gov (United States)

    Patel, Dhaval; Ellis, Ryan; Howard, Brandi; Boufraqech, Myriem; Gara, Sudheer Kumar; Zhang, Lisa; Quezado, Martha M; Nilubol, Naris; Kebebew, Electron

    2014-10-01

    Adrenocortical carcinoma (ACC) lacks diagnostic and prognostic biomarkers to guide treatment. A consistently dysregulated pathway in ACC is the IGF signaling pathway, specifically overexpression of IGF2, IGF-I-receptor, and IGFBP2. The objective of this study was to perform a comprehensive analysis of serum IGF and IGFBP levels and to determine their utility as diagnostic and prognostic biomarkers in ACC. Preoperative serum samples from 53 patients who underwent surgery for adrenocortical adenomas, 3 patients who underwent initial surgery for ACC, 16 patients who underwent reoperative surgery for ACC, and 5 healthy volunteer controls were analyzed. The serum concentration of IGF1, IGF2, IGFBP1, IGFBP2, and IGFBP3 was determined by enzyme-linked immunosorbent assay. No difference in the levels of IGF2 (p = .231) and IGFBP2 (p = .511) was observed between patients with ACC, benign adrenocortical tumors, and healthy volunteers. IGF1, IGFBP1, and IGFBP3 levels were not detected. High IGFBP2 levels were associated with better overall survival (OS) (p = .001) and showed a trend toward better abdominal progression-free (APFS) survival (p = .070) in patients with ACC. A subanalysis of patients undergoing reoperation for recurrent ACC showed better OS with high levels of IGFBP2 (p = .003) and a trend toward better APFS (p = .107). There was no significant difference in IGF2 and IGFBP2 levels by extent of disease. IGF2 and IGFBP2 are not elevated in the serum of patients with ACC compared with patients with benign neoplasms and healthy volunteers. Elevated serum IGFBP2 is associated with better survival in patients with ACC and those undergoing reoperative surgery for recurrent ACC.

  7. Potential of Treatment-Specific Protein Biomarker Profiles for Detection of Hormone Abuse in Cattle

    NARCIS (Netherlands)

    Ludwig, S.K.J.; Smits, N.G.E.; Cannizzo, F.T.; Nielen, M.W.F.

    2013-01-01

    Targeted protein biomarker profiling is suggested as a fast screening approach for detection of illegal hormone treatment in meat production. The advantage of using biomarkers is that they mark the biological response and, thus, are responsive to a panel of substances with similar effects. In a

  8. Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

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    Zhigang Hu

    2016-01-01

    Full Text Available Vascular adhesion protein-1 (VAP-1 is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules and subgroup 2 (57 cases with thyroid cancer. Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg levels in thyroid cancer patients (r=-0.81; p<0.001. The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer.

  9. Serum microRNAs as biomarkers of human lymphocyte activation in health and disease.

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    Paola ede Candia

    2014-02-01

    Full Text Available Induction of the adaptive immune system is evaluated mostly by assessment of serum antibody titers and T lymphocyte responses in peripheral blood, although T and B cell activation occurs in lymphoid tissues. In recent years, the release of microRNAs (miRNAs in the extra-cellular environment has been exploited to assess cell functions at distance via measurement of serum miRNAs. Also activated lymphocytes release a large amount of nano-sized vesicles (exosomes, containing miRNA, but there are still few data on whether this phenomenon is reflected in modulation of serum miRNAs. Interestingly, miRNA signatures of CD4+ T cell-derived exosomes are substantially different from intracellular miRNA signatures of the same cells. We have recently identified serum circulating miR-150 as a sensor of general lymphocyte activation and we strongly believe that the identification of miRNAs differentially released by specific CD4+ effector T cell subsets (Th1, Th2, Th17 and Treg may work as serum biomarkers of their elicitation in lymphoid tissues but also in damaged tissues, thus providing pivotal information about the nature of immune responses occurring in health and disease.

  10. Impact of Serum Estradiol on Biomarkers of Oxidative Stress in Polycystic Ovary Syndrome and Ovulatory Women

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    Dana M. Block-Abraham

    2012-01-01

    Full Text Available Background Estrogens are thought to possess antioxidant properties in vivo, with estradiol being the most biologically active and available. Unlike ovulatory women, those with polycystic ovary syndrome (PCOS have a relative steady-state serum estradiol concentration across a typical month. To better understand the antioxidant role of serum estradiol in premenopausal women, we evaluated biomarkers of oxidative stress at two time points in both ovulatory and anovulatory cycles (ie, women with PCOS. Methods A total of 16 women (7 PCOS, 9 ovulatory completed this study. Ovulatory women were tested on cycle day 3, and again on cycle day 21. Women with PCOS were tested at a random time and returned to the clinic 14 days later. At each visit, blood was collected for determination of malondialdehyde (MDA, hydrogen peroxide (H 2 O 2 and Trolox Equivalent Antioxidant Capacity (TEAC. Estradiol, progesterone, luteinizing hormone (LH, and follicle-stimulating hormone (FSH were also measured. Results There were no significant differences observed in any oxidative stress biomarker between ovulatory and PCOS women. Estradiol levels were positively correlated with TEAC in women with PCOS (r = 0.57; P = 0.03, but not in ovulatory women. While not statistically significant, negative correlations were noted between estradiol and MDA and estradiol and H 2 O 2 in women with PCOS but not in ovulatory subjects. Conclusions Our data indicate that oxidative stress biomarkers do not differ between PCOS and ovulatory women. The changing estrogen level that occurs throughout ovulatory cycles does not appear to impact overall oxidative status when compared to the relative steady-state estradiol levels in PCOS subjects in our study. Furthermore, estradiol may be associated with antioxidant status and biomarkers of oxidative stress in women with PCOS but not in those with regular menstrual cycles.

  11. Serum microRNAs as novel biomarkers for primary sclerosing cholangitis and cholangiocarcinoma.

    Science.gov (United States)

    Bernuzzi, F; Marabita, F; Lleo, A; Carbone, M; Mirolo, M; Marzioni, M; Alpini, G; Alvaro, D; Boberg, K M; Locati, M; Torzilli, G; Rimassa, L; Piscaglia, F; He, X-S; Bowlus, C L; Yang, G-X; Gershwin, M E; Invernizzi, P

    2016-07-01

    The diagnosis of primary sclerosing cholangitis (PSC) is difficult due to the lack of sensitive and specific biomarkers, as is the early diagnosis of cholangiocarcinoma (CC), a complication of PSC. The aim of this study was to identify specific serum miRNAs as diagnostic biomarkers for PSC and CC. The levels of 667 miRNAs were evaluated in 90 human serum samples (30 PSC, 30 CC and 30 control subjects) to identify disease-associated candidate miRNAs (discovery phase). The deregulated miRNAs were validated in an independent cohort of 140 samples [40 PSC, 40 CC, 20 primary biliary cirrhosis (PBC) and 40 controls]. Receiver operating characteristic (ROC) curves were established and only miRNAs with an area under the curve (AUC) > 0·70 were considered useful as biomarkers. In the discovery phase we identified the following: 21 miRNAs expressed differentially in PSC, 33 in CC and 26 in both in comparison to control subjects as well as 24 miRNAs expressed differentially between PSC and CC. After the validation phase, miR-200c was found to be expressed differentially in PSC versus controls, whereas miR-483-5p and miR-194 showed deregulated expression in CC compared with controls. We also demonstrate a difference in the expression of miR-222 and miR-483-5p in CC versus PSC. Combination of these specific miRNAs further improved the specificity and accuracy of diagnosis. This study provides a basis for the use of miRNAs as biomarkers for the diagnosis of PSC and CC. © 2016 British Society for Immunology.

  12. Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study

    DEFF Research Database (Denmark)

    Silkoff, P E; Strambu, I; Laviolette, M

    2015-01-01

    BACKGROUND: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This re...

  13. Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

    Science.gov (United States)

    Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

    2016-01-01

    We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Tissue compartment analysis for biomarker discovery by gene expression profiling.

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    Antoine Disset

    Full Text Available BACKGROUND: Although high throughput technologies for gene profiling are reliable tools, sample/tissue heterogeneity limits their outcomes when applied to identify molecular markers. Indeed, inter-sample differences in cell composition contribute to scatter the data, preventing detection of small but relevant changes in gene expression level. To date, attempts to circumvent this difficulty were based on isolation of the different cell structures constituting biological samples. As an alternate approach, we developed a tissue compartment analysis (TCA method to assess the cell composition of tissue samples, and applied it to standardize data and to identify biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: TCA is based on the comparison of mRNA expression levels of specific markers of the different constitutive structures in pure isolated structures, on the one hand, and in the whole sample on the other. TCA method was here developed with human kidney samples, as an example of highly heterogeneous organ. It was validated by comparison of the data with those obtained by histo-morphometry. TCA demonstrated the extreme variety of composition of kidney samples, with abundance of specific structures varying from 5 to 95% of the whole sample. TCA permitted to accurately standardize gene expression level amongst >100 kidney biopsies, and to identify otherwise imperceptible molecular disease markers. CONCLUSIONS/SIGNIFICANCE: Because TCA does not require specific preparation of sample, it can be applied to all existing tissue or cDNA libraries or to published data sets, inasmuch specific operational compartments markers are available. In human, where the small size of tissue samples collected in clinical practice accounts for high structural diversity, TCA is well suited for the identification of molecular markers of diseases, and the follow up of identified markers in single patients for diagnosis/prognosis and evaluation of therapy efficiency. In laboratory

  15. Serum Calcium Increase Correlates With Worsening of Lipid Profile

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    Gallo, Luigia; Faniello, Maria C.; Canino, Giovanni; Tripolino, Cesare; Gnasso, Agostino; Cuda, Giovanni; Costanzo, Francesco S.; Irace, Concetta

    2016-01-01

    Abstract Despite the well-documented role of calcium in cell metabolism, its role in the development of cardiovascular disease is still under heavy debate. Several studies suggest that calcium supplementation might be associated with an increased risk of coronary heart disease, whereas others underline a significant effect on lowering high blood pressure and hyperlipidemia. The purpose of this study was to investigate, in a large nonselected cohort from South Italy, if serum calcium levels correlate with lipid values and can therefore be linked to higher individual cardiovascular risk. Eight-thousand-six-hundred-ten outpatients addressed to the Laboratory of Clinical Biochemistry, University of Magna Græcia, Catanzaro, Italy from January 2012 to December 2013 for routine blood tests, were enrolled in the study. Total HDL-, LDL- and non-HDL colesterol, triglycerides, and calcium were determined with standard methods. We observed a significant association between total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL cholesterol, triglycerides, and serum calcium in men and postmenopause women. Interestingly, in premenopause women, we only found a direct correlation between serum calcium, total cholesterol, and HDL-cholesterol. Calcium significantly increased while increasing total cholesterol and triglycerides in men and postmenopause women. Our results confirm that progressive increase of serum calcium level correlates with worsening of lipid profile in our study population. Therefore, we suggest that a greater caution should be used in calcium supplement prescription particularly in men and women undergoing menopause, in which an increase of serum lipids is already known to be associated with a higher cardiovascular risk. PMID:26937904

  16. Identification of serum microRNA biomarkers for tuberculosis using RNA-seq.

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    Hongtai Zhang

    Full Text Available Tuberculosis (TB remains a significant human health issue. More effective biomarkers for use in tuberculosis prevention, diagnosis, and treatment, including markers that can discriminate between healthy individuals and those with latent infection, are urgently needed. To identify a set of such markers, we used Solexa sequencing to examine microRNA expression in the serum of patients with active disease, healthy individuals with latent TB, and those with or without prior BCG inoculation. We identified 24 microRNAs that are up-regulated (2.85-1285.93 fold and 6 microRNAs that are down-regulated (0.003-0.11 fold (P<0.05 in patients with active TB relative to the three groups of healthy controls. In addition, 75 microRNAs were up-regulated (2.05-2454.58 fold and 11 were down-regulated (0.001-0.42 fold (P<0.05 in latent-TB infected individuals relative to BCG- inoculated individuals. Of interest, 134 microRNAs were differentially-expressed in BCG-inoculated relative to un-inoculated individuals (18 up-regulated 2.9-499.29 fold, 116 down-regulated 0.0002-0.5 fold, providing insights into the effects of BCG inoculation at the microRNA level. Target prediction of differentially-expressed microRNAs by microRNA-Gene Network analysis and analysis of pathways affected suggest that regulation of the host immune system by microRNAs is likely to be one of the main factors in the pathogenesis of tuberculosis. qRT-PCR validation indicated that hsa-miR-196b and hsa-miR-376c have potential as markers for active TB disease. The microRNA differential-expression profiles generated in this study provide a good foundation for the development of markers for TB diagnosis, and for investigations on the role of microRNAs in BCG-inoculated and latent-infected individuals.

  17. MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy

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    Qi Lu

    2017-05-01

    Full Text Available Background: Ectopic pregnancy (EP refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. Methods: The serum concentrations of 21 microRNAs (miRNAs associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP, 30 patients with spontaneous abortion (SA, and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. Results: Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%. In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%. Conclusion: Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP.

  18. MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy.

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    Lu, Qi; Yan, Qi; Xu, Fengying; Li, Yuhong; Zhao, Wenxia; Wu, Chunzhu; Wang, Yudong; Lang, Xiao

    2017-01-01

    Ectopic pregnancy (EP) refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG) measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. The serum concentrations of 21 microRNAs (miRNAs) associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP), 30 patients with spontaneous abortion (SA), and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%). In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%). Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP. © 2017 The Author(s). Published by S. Karger AG, Basel.

  19. Serum Matrix Metalloproteinase-3 as a Noninvasive Biomarker of Histological Synovitis for Diagnosis of Rheumatoid Arthritis

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    Jian-Da Ma

    2014-01-01

    Full Text Available Objective. To explore the correlation between matrix metalloproteinase- (MMP- 3 and histological synovitis in rheumatoid arthritis (RA. Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenn’s synovitis score r=0.574, P<0.001 and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA r=0.656, P<0.001. Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P<0.05. Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.

  20. Differential Expression of Host Biomarkers in Saliva and Serum Samples from Individuals with Suspected Pulmonary Tuberculosis

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    Khutso G. Phalane

    2013-01-01

    Full Text Available The diagnosis of tuberculosis remains challenging in individuals with difficulty in providing good quality sputum samples such as children. Host biosignatures of inflammatory markers may be valuable in such cases, especially if they are based on more easily obtainable samples such as saliva. To explore the potential of saliva as an alternative sample in tuberculosis diagnostic/biomarker investigations, we evaluated the levels of 33 host markers in saliva samples from individuals presenting with pulmonary tuberculosis symptoms and compared them to those obtained in serum. Of the 38 individuals included in the study, tuberculosis disease was confirmed in 11 (28.9% by sputum culture. In both the tuberculosis cases and noncases, the levels of most markers were above the minimum detectable limit in both sample types, but there was no consistent pattern regarding the ratio of markers in serum/saliva. Fractalkine, IL-17, IL-6, IL-9, MIP-1β, CRP, VEGF, and IL-5 levels in saliva and IL-6, IL-2, SAP, and SAA levels in serum were significantly higher in tuberculosis patients (P<0.05. These preliminary data indicate that there are significant differences in the levels of host markers expressed in saliva in comparison to those expressed in serum and that inflammatory markers in both sample types are potential diagnostic candidates for tuberculosis disease.

  1. Chronic kidney disease may be differentially diagnosed from preeclampsia by serum biomarkers.

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    Rolfo, Alessandro; Attini, Rossella; Nuzzo, Anna M; Piazzese, Annalisa; Parisi, Silvia; Ferraresi, Martina; Todros, Tullia; Piccoli, Giorgina B

    2013-01-01

    Preeclampsia, affecting 5-8% of pregnancies, is the main cause of fetal-maternal mortality and morbidity. The differential diagnosis with chronic kidney disease (CKD) is a challenge owing to the overlapping clinical features. No biomarker has been found to discriminate between the two conditions. Here, we tested whether maternal serum levels of placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1), markers of preeclampsia, could be used to discriminate between 34 patients with preeclampsia, 23 patients with CKD during pregnancy, and 38 healthy pregnant women. Serum levels of PlGF and sFlt-1 were determined during the third trimester by commercially available immunoassays. In preeclampsia, sFlt-1 levels were significantly increased in comparison with that in CKD and in the control women. Serum levels of PlGF in preeclampsia were significantly decreased relative to both controls and patients with CKD. The sFlt-1 to PlGF ratio was significantly increased in preeclampsia (median 436) compared with controls (median 9.4) and CKD (median 4.0). No differences were found between controls and patients with CKD. Thus, our study suggests that it is possible to discriminate between preeclampsia and CKD during pregnancy by determining maternal serum levels of sFlt-1 and PlGF and their ratio.

  2. Profiling of cytokines, chemokines and other soluble proteins as a potential biomarker in colorectal cancer and polyps.

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    Johdi, Nor Adzimah; Mazlan, Luqman; Sagap, Ismail; Jamal, Rahman

    2017-11-01

    Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be

  3. SERUM LIPID PROFILE AS AN ETIOLOGY OF VERTIGO : A STUDY

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    Sami

    2015-09-01

    Full Text Available A prospective study of lipid profile was done in 60 patients of vertigo at E.L.M.C. Lucknow from 2011 to 2014. All components of serum cholesterol were analyzed. Serum cholesterol and hyperlipidemia as an etiology of the atherosclerosis of all blood vessel s also have a role in vestibulo - cochlear vessels. It was found that there were 34 females and 26 males and maximum number of patients (63.33% in the age group of 31 - 50years. Appreciable difference (p<0.05 in the mean value of total lipid, total cholester ol, triglycerides and phospholipids in the control and study group was found but difference was not significant in the mean value of HDL, LDL and VLDL cholesterol level. Four cases of diabetes and ten cases of hypertension of 60 vertigo cases were having m arked vertigo of longer duration. These findings were similar to Mehra Y.N. Thus we find that serum lipid studies are important in the patients of vertigo for the diagnosis and management

  4. Serum and bronchoalveolar lavage fluid endothelin-1 concentrations as diagnostic biomarkers of canine idiopathic pulmonary fibrosis.

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    Krafft, E; Heikkilä, H P; Jespers, P; Peeters, D; Day, M J; Rajamäki, M M; Mc Entee, K; Clercx, C

    2011-01-01

    Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin-1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown. To evaluate whether measurement of the concentration of ET1 in serum and bronchoalveolar lavage fluid (BALF) can be used to distinguish canine IPF from chronic bronchitis (CB) and eosinophilic bronchopneumopathy (EBP). Twelve dogs with IPF, 10 dogs with CB, 6 dogs with EBP, 13 privately owned healthy West Highland White Terriers (WHWT), and 9 healthy Beagle dogs. Prospective, case control study. ET1 concentration was determined by ELISA in serum and in BALF. No significant difference in serum ET1 concentration was detected between healthy Beagle dogs and WHWT. Serum ET1 concentration was higher in dogs with IPF (median interquartile range; 2.32 pg/mL, 2.05-3.38) than healthy Beagle dogs (1.28, 1.07-1.53; P < .001), healthy WHWT (1.56, 1.25-1.85; P < .001), dogs with EBP (0.94 0.68-1.01; P = .001), and dogs with CB (1.54 0.74-1.82; P = .005). BALF ET1 concentration was below the detection limit in healthy WHWT and in dogs with CB, whereas it was measurable in all dogs with IPF. A cut-off serum concentration of 1.8 pg/mL had a sensitivity of 100% and a specificity of 81.2% for detection of IPF, with an area under the receiver operating characteristic curve of 0.818. Serum ET1 can differentiate dogs with IPF from dogs with EBP or CB. ET1 can be detected in BALF of dogs with IPF. Copyright © 2011 by the American College of Veterinary Internal Medicine.

  5. Evaluation the Effect Garlet Tablet on Serum Lipid Profile

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    F. Emami

    2006-07-01

    Full Text Available Introduction & Objective: Some investigators reported significant effect of garlic on serum cholesterol reduction. In addition, Iranian culture has specific belief on herbs and garlic in this regard. Our goal in this study was to evaluate the effect of garlet tablets on serum lipid profile.Materials & Methods: Sixty patients were randomly divided into two groups for evaluation of the effect of garlic on their lipid profile. The first group was low fat regimen group and the second was garlet tablet regimen group. Total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels were measured in both groups. Then, after two months of these regimens administration, these items were measured again and were compared.Results: Mean age, sex and baseline initial lipid levels were similar in both groups. Total cholesterol and LDL cholesterol levels were decreased significantly in the garlic regimen group (in spite of non significant reduction in the other group. Triglyceride and HDL levels were not changed significantly in both regimen groups. Conclusion: Garlet tablet administration has more significant reductive effect on cholestrol level than low cholesterol diet.

  6. Low serum leptin serves as a biomarker of malnutrition in elderly patients.

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    Amirkalali, Bahareh; Sharifi, Farshad; Fakhrzadeh, Hossein; Mirarefein, Mojde; Ghaderpanahi, Maryam; Badamchizadeh, Zohreh; Larijani, Bagher

    2010-05-01

    Anthropometric and classical biologic markers of malnutrition, such as serum albumin, are limited because they are influenced by nonnutritional factors. We propose that a biologic parameter that both predicts nutritional status and is unaffected by nonnutritional factors would facilitate the diagnosis of malnutrition in the elderly. This cross-sectional study included 179 randomized elderly patients. Nutritional status was assessed by the Mini-Nutritional Assessment (MNA) instrument; other end points included anthropometric measures and biologic parameters. Subjects were divided into 3 groups based on MNA-defined nutritional status, and end point means were compared using 2-way analyses of variance adjusted by sex. Correlations between the most accurate biologic marker in predicting malnutrition and other biologic and clinical variables were assessed using Pearson correlation test. Multiple linear regressions were then performed to relate the best biomarker of malnutrition to specific parameters. Finally, leptin levels that predict malnutrition were determined using receiver operating characteristic curve cutoff values. The well-nourished group had significantly higher leptin (P = .001), weight, body mass index, mid-arm circumference, and calf circumference (all, P malnourished group and the at risk of malnutrition group. Serum leptin was the optimal biomarker of MNA-defined malnutrition and had significant positive correlations with weight (P = .003) and with all anthropometric values (all P elderly patients. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Serum biomarker screening for the diagnosis of early gastric cancer using SELDI-TOF-MS.

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    Li, Ping; Zhang, Dianliang; Guo, Chunbao

    2012-06-01

    In this study, we performed a proteomic analysis of sera from stage I gastric cancer patients using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and established a diagnostic model for the early diagnosis of stage I gastric cancer. Serum samples from 169 gastric cancer patients and 83 age- and gender-matched healthy individuals were analyzed by SELDI-TOF-MS ProteinChip array technology. The SELDI-TOF-MS spectral data were analyzed using the Biomarker Wizard™ and Biomarker Patterns™ software to find differential proteins and develop a classification tree for gastric cancer. A total of 34 mass peaks were identified. Six peaks at a mass-to-charge ratio (m/z) of 2873, 3163, 4526, 5762, 6121 and 7778 were used to construct the diagnostic model. The model effectively distinguished gastric cancer samples from control samples, achieving a sensitivity and specificity of 93.49 and 91.57%, respectively. In addition, we identified 3 of the 6 protein peaks at 2873, 6121 and 7778 m/z, which distinguished between stage I and stage II/III/IV gastric cancer. The model had an accuracy of 88.89% for the identification of stage I gastric cancer. In conclusion, the diagnostic model for the detection of serum proteins by SELDI-TOF-MS ProteinChip array technology correctly distinguishes gastric cancer from healthy samples, and has the ability to screen and distinguish between early gastric cancer from advanced gastric cancer.

  8. Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children

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    Wiredu Edwin K

    2007-11-01

    Full Text Available Abstract Background Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM, a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. Methods Postmortem serum and cerebrospinal fluid (CSF samples were obtained within 2–4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA, and non-malarial (NM causes. Serum and CSF levels of 36 different biomarkers (IL-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70, IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-γ, TNF-α, IP-10, MCP-1 (MCAF, MIP-1α, MIP-1β, RANTES, SDF-1α, CXCL11 (I-TAC, Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55, sTNF-R2 (p75, MMP-9, TGF-β1, PDGF bb and VEGF were measured and the results compared between the 3 groups. Results After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1β, Fas-L, sTNF-R1, and sTNF-R2 were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. Conclusion The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1β, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting

  9. Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis: A cross-sectional study.

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    Sanaei Dashti, Anahita; Alizadeh, Shekoofan; Karimi, Abdullah; Khalifeh, Masoomeh; Shoja, Seyed Abdolmajid

    2017-09-01

    There are many difficulties distinguishing bacterial from viral meningitis that could be reasonably solved using biomarkers. The aim of this study was to evaluate lactate, procalcitonin (PCT), ferritin, serum-CRP (C-reactive protein), and other known biomarkers in differentiating bacterial meningitis from viral meningitis in children.All children aged 28 days to 14 years with suspected meningitis who were admitted to Mofid Children's Hospital, Tehran, between October 2012 and November 2013, were enrolled in this prospective cross-sectional study. Children were divided into 2 groups of bacterial and viral meningitis, based on the results of cerebrospinal fluid (CSF) culture, polymerase chain reaction, and cytochemical profile. Diagnostic values of CSF parameters (ferritin, PCT, absolute neutrophil count [ANC], white blood cell count, and lactate) and serum parameters (PCT, ferritin, CRP, and erythrocyte sedimentation rate [ESR]) were evaluated.Among 50 patients with meningitis, 12 were diagnosed with bacterial meningitis. Concentrations of all markers were significantly different between bacterial and viral meningitis, except for serum (P = .389) and CSF (P = .136) PCT. The best rates of area under the receiver operating characteristic (ROC) curve (AUC) were achieved by lactate (AUC = 0.923) and serum-CRP (AUC = 0.889). The best negative predictive values (NPV) for bacterial meningitis were attained by ANC (100%) and lactate (97.1%).The results of our study suggest that ferritin and PCT are not strong predictive biomarkers. A combination of low CSF lactate, ANC, ESR, and serum-CRP could reasonably rule out the bacterial meningitis.

  10. Serum anti-Helicobacter pylori immunoglobulin G titer correlates with grade of histological gastritis, mucosal bacterial density, and levels of serum biomarkers.

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    Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Yuan, Yuan

    2014-03-01

    OBJECTIVE. Clinical implications of serum anti-Helicobacter pylori immunoglobulin G (IgG) titer were unclear. This study investigated the associations of serum anti-H. pylori IgG titer with grade of histological gastritis, mucosal bacterial density and levels of serum biomarkers, including pepsinogen (PG) I, PGII, PGI/II ratio and gastrin-17. MATERIAL AND METHODS. Study participants were from a screening program in northern China. Serum anti-H. pylori IgG measurements were available for 5922 patients with superficial gastritis. Serum anti-H. pylori IgG titer and serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized criteria. RESULTS. In patients with mild, moderate or severe superficial gastritis, the mean serum anti-H. pylori IgG titers were 17.3, 33.4 and 54.4 EIU (p for trend gastritis, mucosal bacterial density and concentrations of serum PGI, PGII and gastrin-17, and negatively with PGI/II ratio.

  11. Potential serum biomarkers associated with mild and severe leptospirosis infection: A cohort study in the Malaysian population.

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    Tan, Xue Ting; Amran, Fairuz Binti; Thayan, Ravindran; Ahmad, Norazah; Jaafar, Roslinda; Haron, Rahimah; Abdullah, Rafidah; Bin Shamsuddin, Sazwan Reezal; Md Riffin, Nor Suhaila Binti; Abdul-Rahman, Puteri Shafinaz

    2017-09-01

    Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild nonspecific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, 15 paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS. The expression of proteins that were significantly different and had a fold difference of at least 2 had been identified and then validated using Western blot. Our study demonstrated apolipoprotein A-I (APOA-I), serum amyloid A (SAA), transferrin (TF), haptoglobin (HP) and transthyretin (TTR) have significantly different expression between mild and severe leptospirosis. The Ingenuity Pathway Analysis software suggested the expression of these five proteins were modulated by acute phase response signaling pathway. Besides that, a functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects these five proteins with interactomes also had been predicted by this software. In conclusion, this finding supports the potential of these five proteins to be the biomarkers for mild and severe human leptospirosis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. The thymus and activation-regulated chemokine (TARC level in serum at an early stage of a drug eruption is a prognostic biomarker of severity of systemic inflammation

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    Takayoshi Komatsu-Fujii

    2018-01-01

    Conclusions: Serum TARC levels correlate well with indicators of systemic inflammation and of disease severity among patients with a drug eruption except SJS/TEN. Serum TARC may be a prognostic biomarker of severity of inflammation in drug eruptions.

  13. Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.

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    Sheng, Jonathan; Wang, Yi; Turesky, Robert J; Kluetzman, Kerri; Zhang, Qing-Yu; Ding, Xinxin

    2016-05-16

    Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans.

  14. Soluble MUC1 and serum MUC1-specific antibodies are potential prognostic biomarkers for platinum-resistant ovarian cancer.

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    Budiu, Raluca A; Mantia-Smaldone, Gina; Elishaev, Esther; Chu, Tianjiao; Thaller, Julia; McCabe, Kathryn; Lenzner, Diana; Edwards, Robert P; Vlad, Anda M

    2011-07-01

    MUC1 (CA15-3) and MUC16 (CA125) tumor-associated antigens are upregulated in ovarian cancer and can be detected in patients' sera by standardized tests. We postulated that increased MUC1 and MUC16 antigens augment antibody responses in platinum-resistant ovarian cancer patients and that the frequency and intensity of these responses can be used as immune biomarkers of treatment response and disease outcome. We measured MUC1 and MUC16 tumor expression by immunohistochemistry (IHC), assessed serum antigenic levels and quantitated circulating antibodies by ELISA in a cohort of 28 ovarian cancer patients with platinum-resistant or platinum-refractory ovarian cancer, and treated with intraperitoneal (IP) interleukin-2 (IL-2). MUC1 and MUC16 were overexpressed in tumor samples and showed differential distribution profiles. Serum MUC1 (CA15-3) measurements were elevated in all patients and significantly correlated with increased risk of death (P = 0.003). MUC1-specific IgM and IgG anitbodies were found in 92 and 50% of cases, respectively. Patients with progressive disease had higher mean anti-MUC1 IgG than responders at both early (P = 0.025) and late (P = 0.022) time points during IP IL-2 treatment. Anti-MUC1 IgM antibodies inversely correlated with overall survival at both early (P = 0.052) and late (P = 0.009) time points. In contrast to MUC1, neither soluble MUC16 nor MUC16-specific antibodies were significantly associated with clinical response or overall survival in this study. Increased serum MUC1 and high anti-MUC1 antibody levels are prognostic for poor clinical response and reduced overall survival in platinum-resistant or platinum-refractory ovarian cancer.

  15. Mapping CSF biomarker profiles onto NIA-AA guidelines for Alzheimer's disease.

    Science.gov (United States)

    Alexopoulos, Panagiotis; Roesler, Jennifer; Thierjung, Nathalie; Werle, Lukas; Buck, Dorothea; Yakushev, Igor; Gleixner, Lena; Kagerbauer, Simone; Ortner, Marion; Grimmer, Timo; Kübler, Hubert; Martin, Jan; Laskaris, Nikolaos; Kurz, Alexander; Perneczky, Robert

    2016-10-01

    The National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines for Alzheimer's disease (AD) propose the categorization of individuals according to their biomarker constellation. Though the NIA-AA criteria for preclinical AD and AD dementia have already been applied in conjunction with imaging AD biomarkers, the application of the criteria using comprehensive cerebrospinal fluid (CSF) biomarker information has not been thoroughly studied yet. The study included a monocentric cohort with healthy (N = 41) and disease (N = 22) controls and patients with AD dementia (N = 119), and a multicentric sample with healthy controls (N = 116) and patients with AD dementia (N = 102). The CSF biomarkers β-amyloid 1-42, total tau, and phosphorylated tau at threonine 181 were measured with commercially available assays. Biomarker values were trichotomized into positive for AD, negative, or borderline. In controls the presence of normal CSF profiles varied between 13.6 and 25.4 % across the studied groups, while up to 8.6 % of them had abnormal CSF biomarkers. In 40.3-52.9 % of patients with AD dementia, a typical CSF profile for AD was detected. Approximately 40 % of the potential biomarker constellations are not considered in the NIA-AA guidelines, and more than 40 % of participants could not be classified into the NIA-AA categories with distinct biomarker constellations. Here, a refined scheme covering all potential biomarker constellations is proposed. These results enrich the discussion on the NIA-AA guidelines and point to a discordance between clinical symptomatology and CSF biomarkers even in patients with full-blown AD dementia, who are supposed to have a clearly positive for AD neurochemical profile.

  16. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  17. Serial Sampling of Serum Protein Biomarkers for Monitoring Human Traumatic Brain Injury Dynamics: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Eric Peter Thelin

    2017-07-01

    Full Text Available BackgroundThe proteins S100B, neuron-specific enolase (NSE, glial fibrillary acidic protein (GFAP, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1, and neurofilament light (NF-L have been serially sampled in serum of patients suffering from traumatic brain injury (TBI in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term “effective half-life” (t1/2 in order to describe the “fall” rate in serum.Materials and methodsThrough searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations.ResultsFollowing screening (10,389 papers, n = 122 papers were included. The proteins S100B (n = 66 and NSE (n = 27 were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1–2 h though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18 appears to have t1/2 of about 24–48 h in severe TBI. The protein UCH-L1 (n = 9 presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2 only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use.ConclusionSerial sampling of brain-specific proteins in serum reveals

  18. Serum Proteomic Profiling of Obsessive-Compulsive Disorder, Washing Subtype: A Preliminary Study

    Science.gov (United States)

    Zamanian-Azodi, Mona; Rezaei-Tavirani, Mostafa; Nejadi, Naser; Arefi Oskouie, Afsaneh; Zayeri, Faird; Hamdieh, Mostafa; Safaei, Akram; Rezaei-Tavirani, Majid; Ahmadzadeh, Alireza; Amouzandeh-Nobaveh, Alireza; Okhovatian, Farshad

    2017-01-01

    Introduction: Obsessive-Compulsive Disorder (OCD) is a disabling mental condition that its proteomic profiling is not yet investigated. Proteomics is a valuable tool to discover biomarker approaches. It can be helpful to detect protein expression changes in complex disorders such as OCD. Methods: Here, by the application of 2D gel electrophoresis (2DE), a pilot study of serum proteome profile of females with washing subtype of OCD was performed. Serum samples were obtained from females with washing subtype of OCD. Following the protein extraction from the serum with acetone perception, the samples were subjected to 2DE for separation based on pI and molecular weight (MW) with triple replications. Finally, the protein spots were visualized using Coomassie blue staining method and analyzed by Progenesis SameSpots software. Furthermore, protein-protein interaction (PPI) network analysis was handled by the application of Cytoscape software. Results: The results suggested that 41 matched spots demonstrated significant expression alterations among which 5 proteins including immunoglobulin heavy constant alpha-1 (IGHA1), apolipoprotein A-4 (APOA4), haptoglobin (HP), protein α-1-antitrypsin (SERPINA1), and component 3 (C3) were identified by database query. Additionally, PPI network analysis indicated the central role of SERPINA1 and C3 in the network integrity. However, albumin (ALB), amyloid precursor protein (APP), and protein α-1-antitrypsin (APOA1) proteins were important in OCD PPI network as well. The identified proteins were related to 3 processes: acute-phase response, hydrogen peroxide catabolic process, and regulation of triglyceride metabolic process. Conclusion: It was concluded that these proteins may have a fundamental role in OCD pathogenesis. Moreover, the dysregulation of inflammatory and antioxidant systems in OCD risk was suggested by the current study. However, evaluation of bigger sample sizes and application of mass spectrometry are essential

  19. Effects of Sesame Seed Supplementation on Lipid Profile and Oxidative Stress Biomarkers in Patients with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Mahdieh Khadem Haghighian

    2014-07-01

    Full Text Available Background: This study was designed to assess the effect of sesame seed on lipid profile and oxidative stress biomarkers in knee osteoarthritis (OA patients. Methods: Fifty patients with knee OA were allocated into two groups receiving 40 g of sesame seed daily along with standard medical therapy (n=25 or standard treatment (n=25 for two months. Serum total antioxidant capacity, malondialdehyde (MDA and lipid profile (total cholesterol (TC, HDL-cholesterol, LDL-cholesterol, triglycerides were measured. Results: After the intervention period two months of study, serum TC, LDL-cholesterol and MDA decreased significantly in the sesame group (P0.05. There was no significant difference in pre and post-treatment values of lipid profile and oxidative parameters between the two groups (P>0.05. Conclusion: Current study showed a positive effect of sesame seed in improving lipid profile and oxidative stress in patients with knee OA and indicated the fact that sesame seed might be of help to reduce oxidative stress in OA patients.

  20. Biomarker Research in Parkinson's Disease Using Metabolite Profiling

    DEFF Research Database (Denmark)

    Havelund, Jesper F; Heegaard, Niels H H; Færgeman, Nils J K

    2017-01-01

    Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered...

  1. Identification of potential serum biomarkers to predict feed efficiency in young pigs.

    Science.gov (United States)

    Grubbs, J K; Dekkers, J C M; Huff-Lonergan, E; Tuggle, C K; Lonergan, S M

    2016-04-01

    Identification of biomarkers for feed efficiency in livestock will aid in the efficient production of high-quality protein to meet the demands of a growing population. The overall objective of this research was to identify biomarkers in serum for swine feed efficiency and to discover pathways affected by divergent selection for residual feed intake (RFI). Serum was collected from young pigs (between 35 and 42 d of age) from 2 lines of pigs that have been genetically selected to be either more efficient (low-RFI) or less efficient (high-RFI). After blood collection, during finishing, pigs from each line were placed on either a low-energy/high-fiber diet or a traditional high-energy/low-fiber diet to test for any diet effects on RFI. Subsets of 6 pigs per line within each diet were used in 3 independent experiments. Pigs with extreme RFI phenotypes from the low-energy/high-fiber diet were used to confirm the results from the first 2 comparisons. Two-dimensional difference in gel electrophoresis and mass spectrometry were used to identify proteins with different abundances between RFI line or finishing diet. Three proteins had consistent and significant ( efficient low-RFI pigs (9 to 39%). Vitronectin was also more abundant in the low-RFI pigs (39 to 56%) and has known roles in blood homeostasis and may regulate adiposity. SerpinA3 is a member of a very large family of proteins referred to as serine protease inhibitors. A total of 14 spots that were more abundant in the low-RFI line, some at least twice as abundant, were identified as serpinA3. Multiple isoforms of serpinA3 have been reported (serpinA3-1 to serpinA3-4 in pigs and serpinA3-1 to serpinA3-8 in cattle) with serpinA3 having many different functions dependent on isoform. Gelsolin, vitronectin, and serpinA3 are 3 proteins that may play direct and important biological roles in the pathways that control RFI and, ultimately, feed efficiency through energy utilization and homeostasis. These data demonstrate that

  2. Sex-Specific Associations Between Thyrotropin and Serum Lipid Profiles

    DEFF Research Database (Denmark)

    Meisinger, Christa; Ittermann, Till; Tiller, Daniel

    2014-01-01

    ) cholesterol, and triglycerides in men and women from the general population. Furthermore, the association with TSH outside and within the reference range and lipid levels was studied. METHODS: Individual data of 13,571 men and women without lipid medication of four population-based studies conducted...... with triglyceride values in men and with total cholesterol, LDL cholesterol, and triglyceride values in women. In the pooled male population, low serum TSH levels (... TSH levels within the reference range (0.3-3.0 mIU/L) were significantly positively associated with triglyceride concentrations. CONCLUSIONS: Increasing levels of TSH were associated with a less favorable lipid profile in both men and women from the general population. In both sexes, TSH levels within...

  3. Serum lipid profiles are associated with semen quality

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    Chin-Yu Liu

    2017-01-01

    Full Text Available We aimed to explore the associations between different lipid profiles and semen quality in a large-scale general male population. Sperm concentration, total sperm motility, progressive motility, and normal sperm morphology of total 7601 participants were recorded. The association of these semen parameters with the triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein of serum lipid profiles was analyzed. Sperm concentration was statistically positively correlated with triglyceride and very low-density lipoprotein (adjusted P = 0.001 and P = 0.005, respectively. Total sperm motility and progressive motility were statistically increased with increasing low-density lipoprotein and cholesterol levels (both adjusted P = 0.008 and P < 0.001, respectively. The similar J-shaped associations (high-low-low-high were noted between individual lipid profile and normal sperm morphology, especially low-density lipoprotein and cholesterol with statistical significance (adjusted P = 0.017 and P = 0.021, respectively. The prevalence of abnormal total sperm motility and progressive motility was decreased in participants with high levels of cholesterol (P = 0.008 and P = 0.019, respectively, and the reverse J-shaped associations (low-high-high-low were noted between high-density lipoprotein, triglyceride, very low-density lipoprotein, and the prevalence of abnormal normal sperm morphology (P = 0.010, P = 0.037, and P = 0.025, respectively. A high cholesterol level was associated with better sperm motility. Similar J-shaped associations were noted between all lipid profiles and normal sperm morphology; meanwhile, the reverse J-shaped trends were identified between them and abnormal normal sperm morphology prevalence.

  4. Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination

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    Takao Itoi

    2017-04-01

    Full Text Available This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC from malignant diseases, such as biliary tract cancer (BTC, intraductal papillary mucinous carcinoma (IPMC, and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41 of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140. Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel–Dwass test. Four multiple logistic regression models (MLR were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC of 0.970 (95% confidential interval (CI, 0.946–0.994, p < 0.0001. Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650–1.01, p = 0.0020 with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, pancreatic cancer-associated antigen (DUPAN2 and s-pancreas-1 antigen (SPAN1. Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

  5. Identifying Urinary and Serum Exosome Biomarkers for Radiation Exposure Using a Data Dependent Acquisition and SWATH-MS Combined Workflow

    Energy Technology Data Exchange (ETDEWEB)

    Kulkarni, Shilpa [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Koller, Antonius [Proteomics Center, Stony Brook University School of Medicine, Stony Brook, New York (United States); Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Mani, Kartik M. [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wen, Ruofeng [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York (United States); Alfieri, Alan; Saha, Subhrajit [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); Wang, Jian [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Patel, Purvi [Proteomics Shared Resource, Herbert Irving Comprehensive Cancer Center, New York, New York (United States); Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York (United States); Bandeira, Nuno [Center for Computational Mass Spectrometry, University of California, San Diego, California (United States); Department of Computer Science and Engineering, University of California, San Diego, California (United States); Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, California (United States); Guha, Chandan, E-mail: cguha@montefiore.org [Department of Radiation Oncology, Albert Einstein College of Medicine, Bronx, New York (United States); and others

    2016-11-01

    Purpose: Early and accurate assessment of radiation injury by radiation-responsive biomarkers is critical for triage and early intervention. Biofluids such as urine and serum are convenient for such analysis. Recent research has also suggested that exosomes are a reliable source of biomarkers in disease progression. In the present study, we analyzed total urine proteome and exosomes isolated from urine or serum for potential biomarkers of acute and persistent radiation injury in mice exposed to lethal whole body irradiation (WBI). Methods and Materials: For feasibility studies, the mice were irradiated at 10.4 Gy WBI, and urine and serum samples were collected 24 and 72 hours after irradiation. Exosomes were isolated and analyzed using liquid chromatography mass spectrometry/mass spectrometry-based workflow for radiation exposure signatures. A data dependent acquisition and SWATH-MS combined workflow approach was used to identify significantly exosome biomarkers indicative of acute or persistent radiation-induced responses. For the validation studies, mice were exposed to 3, 6, 8, or 10 Gy WBI, and samples were analyzed for comparison. Results: A comparison between total urine proteomics and urine exosome proteomics demonstrated that exosome proteomic analysis was superior in identifying radiation signatures. Feasibility studies identified 23 biomarkers from urine and 24 biomarkers from serum exosomes after WBI. Urinary exosome signatures identified different physiological parameters than the ones obtained in serum exosomes. Exosome signatures from urine indicated injury to the liver, gastrointestinal, and genitourinary tracts. In contrast, serum showed vascular injuries and acute inflammation in response to radiation. Selected urinary exosomal biomarkers also showed changes at lower radiation doses in validation studies. Conclusions: Exosome proteomics revealed radiation- and time-dependent protein signatures after WBI. A total of 47 differentially secreted

  6. Blood Biomarker Profile of TBI-Associated Cognitive Impairment Among Old and Young Veterans

    Science.gov (United States)

    2015-10-01

    SUBJECT TERMS Traumatic brain injury (TBI), dementia, chronic traumatic encephalopathy (CTE), blood biomarkers, aging, cognitive impairment (CI... chronic traumatic encephalopathy (CTE). The goal of this project is to define the biomarker profile of TBI-associated CI in veterans and compare it to...who may benefit from interventions and treatment for CI and its prevention. Key Words Traumatic brain injury (TBI), dementia, chronic traumatic

  7. Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study.

    Science.gov (United States)

    Mankapure, Pritam Kumar; Barpande, Suresh Ramchandra; Bhavthankar, Jyoti Dilip; Mandale, Manda

    2015-10-01

    Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC) to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1) is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC), but its utility in OSCC has not been confirmed. This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading. Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA) in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA) test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey's multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0. By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (pbig ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729). Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic marker warrants larger prospective studies.

  8. Serum thyroglobulin as a biomarker of iodine deficiency in adult populations

    DEFF Research Database (Denmark)

    Krejbjerg, Anne; Bjergved, Lena; Bülow Pedersen, Inge

    2016-01-01

    OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570...... size and autonomy with low TSH). Others were caused by Tg assay interference (Tg-Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24-h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median...... Tg values compared with nonusers both before and after IF. CONCLUSIONS: Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including...

  9. Longitudinal Bank for Serum, Plasma, and DNA for Detection of Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Vogelzang, Nicolas [Nevada Cancer Inst., Las Vegas, NV (United States); Fink, Louis [Nevada Cancer Inst., Las Vegas, NV (United States)

    2007-11-12

    The discovery of genetic or biochemical markers to discriminate malignant cancers from normal or benign disease states, markers to stage cancer or monitor disease progression and markers that provide an early indication of an individual’s response to chemotherapy have become a major research objectives of the oncology community over the past few years. The goal of the project is to create a patient specimen bank of serum, plasma, urine and tissues from approximately 1500 individuals. The collection of samples from individuals on a longitudinal basis provided proteomic and biochemical data to be correlated with clinical endpoints. This greatly enhanced our ability to identify biomarkers for staging different cancers and to detect patient responsiveness to therapy at an early state in the treatment process.

  10. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

    Directory of Open Access Journals (Sweden)

    Paolo Colomba

    2014-12-01

    Full Text Available Multiple sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these.

  11. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

    Science.gov (United States)

    Colomba, Paolo; Fontana, Simona; Salemi, Giuseppe; Barranca, Marilisa; Lo Sicco, Claudia; Mazzola, Maria Antonietta; Ragonese, Paolo; Savettieri, Giovanni; De Leo, Giacomo; Alessandro, Riccardo; Duro, Giovanni

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these. PMID:25517032

  12. SERUM MAGNESIUM, LIPID PROFILE AND GLYCATED HAEMOGLOBIN IN DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Sunanda Vusikala

    2016-07-01

    Full Text Available BACKGROUND Diabetic retinopathy is one of the important microvascular complications of diabetes mellitus of long duration. Alterations in trace metals like magnesium and lipid profile was observed in diabetic retinopathy with hyperglycaemic status. AIM The study was taken up to assess the role of magnesium, lipid profile and glycated haemoglobin in diabetic retinopathy. MATERIALS AND METHODS A total of 80 subjects between 40-65 years were included in the study. Group 1 includes 20 age and sex matched healthy controls. Group 2 includes 30 cases of Diabetes mellitus without retinopathy. Group 3 includes 30 cases of Diabetes mellitus with retinopathy. RESULTS Magnesium was found to be significantly low in the diabetic group with retinopathy. Serum cholesterol and triglycerides were significantly elevated in the diabetic group with retinopathy. Fasting and Postprandial plasma glucose and glycated haemoglobin (HbA1c levels confirmed the glycaemic status of each of the groups. CONCLUSIONS Hypomagnesemia, hypercholesterolaemia, hypertriglyceridemia was observed in diabetic retinopathy along with increased levels of glycated haemoglobin in our study.

  13. Serum C-reactive protein as a diagnostic biomarker in dogs with bacterial respiratory diseases.

    Science.gov (United States)

    Viitanen, S J; Laurila, H P; Lilja-Maula, L I; Melamies, M A; Rantala, M; Rajamäki, M M

    2014-01-01

    C-reactive protein (CRP) is a major acute-phase protein in dogs. Serum concentrations are low in healthy animals, but increase rapidly after inflammatory stimuli. The aim of the study was to investigate CRP concentrations in various respiratory diseases of dogs and to determine if CRP can be used as a biomarker in the diagnosis of bacterial respiratory diseases. A total of 106 privately owned dogs with respiratory diseases (17 with bacterial tracheobronchitis [BTB], 20 with chronic bronchitis [CB], 20 with eosinophilic bronchopneumopathy [EBP], 12 with canine idiopathic pulmonary fibrosis [CIPF], 15 with cardiogenic pulmonary edema [CPE], and 22 with bacterial pneumonia [BP]) and 72 healthy controls. The study was conducted as a prospective cross-sectional observational study. CRP was measured in serum samples. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and selected diagnostic methods such as cytological and microbiological analysis of respiratory samples, echocardiography, and histopathology. Dogs with BP had significantly higher CRP concentrations (median, 121 mg/L; interquartile range, 68-178 mg/L) than dogs with BTB (23, 15-38, P = .0003), CB (13, 8-14, P < .0001), EBP (5, 5-15, P < .0001), CIPF (17, 10-20, P < .0001), or CPE (19, 13-32, P < .0001) and healthy controls (14, 8-20, P < .0001). Dogs with BTB had significantly higher CRP concentrations than dogs with CB (P = .001) or EBP (P < .0001) and healthy controls (P = .029). These results indicate that CRP has potential for use as an additional biomarker, especially in the diagnostics of BP. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  14. Altered Serum Lipoprotein Profiles in Male and Female Power Lifters Ingesting Anabolic Steroids.

    Science.gov (United States)

    Cohen, Jonathan C.; And Others

    1986-01-01

    Serum lipoprotein profiles were measured in nine male and three female weightlifters who were taking anabolic steroids. The profiles suggest that steriod users may face an increased risk of coronary artery disease. (Author/MT)

  15. Serum cytokine profile in the subclinical form of visceral leishmaniasis

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    Gama M.E.A.

    2004-01-01

    Full Text Available The factors determining the development or not of visceral leishmaniasis (VL have not been completely identified, but a Leishmania-specific cellular immune response seems to play a fundamental role in the final control of infection. Few studies are available regarding the production of cytokines in the subclinical form of VL, with only the production of IFN-g and TNF-a known. The aim of the present study was to identify immunological markers for the oligosymptomatic or subclinical form of VL. A prospective cohort study was conducted on 784 children aged 0 to 5 years from an endemic area in the State of Maranhão, Brazil, between January 1998 and December 2001. During 30 consecutive months of follow-up, 33 children developed the oligosymptomatic form of the disease and 12 the acute form. During the clinical manifestations, serum cytokine levels were determined in 27 oligosymptomatic children and in nine patients with the acute form using a quantitative sandwich enzyme immunoassay. In the subclinical form of VL, variable levels of IL-2 were detected in 52.3% of the children, IL-12 in 85.2%, IFN-g in 48.1%, IL-10 in 88.9%, and TNF-a in 100.0%, with the last two cytokines showing significantly lower levels than in the acute form. IL-4 was not detected in oligosymptomatic individuals. Multiple discriminant analysis used to determine the profile or combination of cytokines predominating in the subclinical form revealed both a Leishmania resistance (Th1 and susceptibility (Th2 profile. The detection of both Th1 and Th2 cytokine profiles explains the self-limited evolution accompanied by the discrete alterations observed for the subclinical form of VL.

  16. Human kallikrein 6 (hK6) : A new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma

    NARCIS (Netherlands)

    Diamandis, EP; Scorilas, A; Fracchioli, S; van Gramberen, M; de Bruijn, H; Henrik, A; Soosaipillai, A; Grass, L; Yousef, GM; Stenman, UH; Massobrio, M; van der Zee, AGJ; Vergote, [No Value; Katsaros, D

    2003-01-01

    Purpose : The discovery of new ovarian cancer biomarkers that are suitable for early disease diagnosis and prognosis may ultimately lead to improved patient management and outcomes. Patients and Methods: We measured, by immunoassay, human kallikrein 6 (hK6) concentration in serum of 97 apparently

  17. Correlation of serum MMP3 and other biomarkers with clinical outcomes in patients with ankylosing spondylitis: A pilot study

    Science.gov (United States)

    The studies aimed to assess a set of biomarkers for their correlations with disease activity/severity of patients with ankylosing spondylitis (AS). A total of 24 AS patients were treated with etanercept and prospectively followed for 12 weeks. Serum levels of TNF-alpha, IFN-gamma, TGF-beta, IL6, IL1...

  18. Serum Protein Profile Study of Clinical Samples Using High Performance Liquid Chromatography-Laser Induced Fluorescence

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Ukendt, Sujatha; Rai, Lavanya

    2009-01-01

    The serum protein profiles of normal subjects, patients diagnosed with cervical cancer, and oral cancer were recorded using High Performance Liquid Chromatography combined with Laser Induced Fluorescence detection (HPLC-LIF). Serum protein profiles of the above three classes were tested...... for establishing the ability of HPLC-LIF protein profiling technique for discrimination, using hard clustering and Fuzzy clustering methods. The clustering algorithms have quite successfully classified the profiles as belonging to normal, cancer of cervix, and oral cancer conditions....

  19. Quantification of NS1 dengue biomarker in serum via optomagnetic nanocluster detection

    DEFF Research Database (Denmark)

    Antunes, Paula Soares Martins; Watterson, Daniel; Parmvi, Mattias

    2015-01-01

    Dengue is a tropical vector-borne disease without cure or vaccine that progressively spreads into regions with temperate climates. Diagnostic tools amenable to resource-limited settings would be highly valuable for epidemiologic control and containment during outbreaks. Here, we present a novel low......-cost automated biosensing platform for detection of dengue fever biomarker NS1 and demonstrate it on NS1 spiked in human serum. Magnetic nanoparticles (MNPs) are coated with high-affinity monoclonal antibodies against NS1 via bio-orthogonal Cu-free 'click' chemistry on an anti-fouling surface molecular...... method. The resulting automated dengue fever assay takes just 8 minutes, requires 6 μL of serum sample and shows a limit of detection of 25 ng/mL with an upper detection range of 20000 ng/mL. The technology holds a great potential to be applied to NS1 detection in patient samples. As the assay...

  20. Effects of Dietary Strawberry Supplementation on Antioxidant Biomarkers in Obese Adults with Above Optimal Serum Lipids

    Directory of Open Access Journals (Sweden)

    Arpita Basu

    2016-01-01

    Full Text Available Berries have shown several cardiovascular health benefits and have been associated with antioxidant functions in experimental models. Clinical studies are limited. We examined the antioxidant effects of freeze-dried strawberries (FDS in adults [n=60; age: 49±10 years; BMI: 36±5 kg/m2 (mean ± SD] with abdominal adiposity and elevated serum lipids. Participants were randomized to one of the following arms: low dose strawberry (25 g/day FDS, low dose control beverage (LD-C, high dose strawberry (50 g/d FDS, and high dose control beverage (HD-C for 12 weeks. Control beverages were matched for calories and total fiber. Plasma antioxidant capacity, trace elements (copper, iron, selenium, and zinc, whole blood glutathione (GSH, and enzyme activity (catalase, glutathione peroxidase, and glutathione reductase were examined at screening (0 week and after 12 weeks’ intervention. At 12 weeks, plasma antioxidant capacity and glutathione levels were higher in the strawberry versus control groups (low and high dose FDS: 45% and 42% for plasma antioxidant capacity and 28% and 36% for glutathione, resp.; glutathione was higher in the high versus low dose strawberry group (all p<0.05. Serum catalase activity was higher in the low dose strawberry (43% versus control group (p<0.01. No differences were noted in plasma trace elements and glutathione enzyme activity. Dietary strawberries may selectively increase plasma antioxidant biomarkers in obese adults with elevated lipids.

  1. Serum Interleukin-6 and CCL11/Eotaxin May Be Suitable Biomarkers for the Diagnosis of Chronic Nonbacterial Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Sigrun Ruth Hofmann

    2017-12-01

    Full Text Available ObjectivesChronic recurrent multifocal osteomyelitis (CRMO, the most severe form of chronic nonbacterial osteomyelitis (CNO, is an autoinflammatory bone disorder. In the absence of diagnostic criteria or biomarkers, CNO/CRMO remains a diagnosis of exclusion. The aim of this study was to identify biomarkers for diagnosing multifocal disease (CRMO.Study designSera from 71 pediatric CRMO patients, 11 patients with osteoarticular infections, 62 patients with juvenile idiopathic arthritis (JIA, 7 patients with para-infectious or reactive arthritis, and 43 patients with acute leukemia or lymphoma, as well as 59 healthy individuals were collected. Multiplex analysis of 18 inflammation- and/or bone remodeling-associated serum proteins was performed. Statistical analysis included univariate ANOVA, discriminant analysis, univariate receiver operating characteristic (ROC analysis, and logistic regression analyses.ResultsFor 14 of 18 blood serum proteins, significant differences were determined between CRMO patients, at least one alternative diagnosis, or healthy controls. Multi-component discriminant analysis delivered five biomarkers (IL-6, CCL11/eotaxin, CCL5/RANTES, collagen Iα, sIL-2R for the diagnosis of CRMO. ROC analysis allowed further reduction to a core set of 2 biomarkers (CCL11/eotaxin, IL-6 that are sufficient to discern between CRMO, healthy controls, and alternative diagnoses.ConclusionSerum biomarkers CCL11/eotaxin and IL-6 differentiate between patients with CRMO, healthy controls, and alternative diagnoses (leukemia and lymphoma, osteoarticular infections, para-infectious arthritis, and JIA. Easily accessible biomarkers may aid in diagnosing CRMO. Further studies testing biomarkers in larger unrelated cohorts are warranted.

  2. Serum androgen profile and physical performance in women Olympic athletes.

    Science.gov (United States)

    Eklund, Emma; Berglund, Bo; Labrie, Fernand; Carlström, Kjell; Ekström, Lena; Hirschberg, Angelica Lindén

    2017-09-01

    The role of endogenous androgens for body composition and physical performance in women athletes is still not elucidated. To examine the serum androgen profile in relation to body composition and physical performance in women Olympic athletes and to compare endocrine variables and body composition to controls. Cross-sectional study, conducted between 2011 and 2015 at the Women's Health Research Unit, Karolinska University Hospital, Stockholm. Swedish women Olympic athletes (n=106) and age-matched and body mass index-matched sedentary controls (n=117) were included in the study. Blood sampling was performed in a rested, fasting state for the measurement of serum androgens and their metabolites by liquid chromatography-tandem mass spectrometry. Body composition was determined by dual-energy X-ray absorptiometry (controls n=100, athletes n=65). The athletes performed standardised performance tests (n=59) (squat jump (SJ) and countermovement jump (CMJ). The athletes demonstrated significantly higher levels of the precursor androgens dehydroepiandrosterone (DHEA) and 5-androstene-3β, 17β-diol (5-DIOL) and the metabolite etiocholanolone glucuronide (Etio-G), significantly lower levels of estrone (pathletes. DHEA and lean mass legs explained 66% of the variance in SJ, whereas lean mass explained 52% of the variance in CMJ. The present data suggest that endogenous androgens are associated with a more anabolic body composition and enhanced performance in women athletes. These results are of importance for the current discussion regarding hyperandrogenism in women athletes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Discovery of the serum biomarker proteins in severe preeclampsia by proteomic analysis

    Science.gov (United States)

    Park, Jisook; Cha, Dong Hyun; Lee, Soo Jae; Kim, Young Nam; Kim, Young Hwan

    2011-01-01

    Preeclapsia (PE) is a severe disorder that occurs during pregnancy, leading to maternal and fetal morbidity and mortality. PE affects about 3-8% of all pregnancies. In this study, we conducted liquid chromatographymass spectrometry/mass spectrometry (LC-MS/MS) to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with AHSG), retinol binding protein 4 (RBP4) and α-1-microglobulin/bikunin (AMBP) and Insulin like growth factor binding protein, acid labile subunit (IGFBP-ALS) were confirmed to be differentially expressed in PE using SRM (P AHSG was verified by ELISA and showed a statistically significant increase in PE samples when compared to controls. PMID:21646846

  4. Evaluation of miR-122 as a Serum Biomarker for Hepatotoxicity in Investigative Rat Toxicology Studies.

    Science.gov (United States)

    Sharapova, T; Devanarayan, V; LeRoy, B; Liguori, M J; Blomme, E; Buck, W; Maher, J

    2016-01-01

    MicroRNAs are short noncoding RNAs involved in regulation of gene expression. Certain microRNAs, including miR-122, seem to have ideal properties as biomarkers due to good stability, high tissue specificity, and ease of detection across multiple species. Recent reports have indicated that miR-122 is a highly liver-specific marker detectable in serum after liver injury. The purpose of the current study was to assess the performance of miR-122 as a serum biomarker for hepatotoxicity in short-term (5-28 days) repeat-dose rat toxicology studies when benchmarked against routine clinical chemistry and histopathology. A total of 23 studies with multiple dose levels of experimental compounds were examined, and they included animals with or without liver injury and with various hepatic histopathologic changes. Serum miR-122 levels were quantified by reverse transcription quantitative polymerase chain reaction. Increases in circulating miR-122 levels highly correlated with serum elevations of liver enzymes, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Statistical analysis showed that miR-122 outperformed ALT as a biomarker for histopathologically confirmed liver toxicity and was equivalent in performance to AST and GLDH. Additionally, an increase of 4% in predictive accuracy was obtained using a multiparameter approach incorporating miR-122 with ALT, AST, and GLDH. In conclusion, serum miR-122 levels can be utilized as a biomarker of hepatotoxicity in acute and subacute rat toxicology studies, and its performance can rival or exceed those of standard enzyme biomarkers such as the liver transaminases. © The Author(s) 2015.

  5. Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects' gender and age.

    Directory of Open Access Journals (Sweden)

    Masaki Ishikawa

    Full Text Available Blood is a commonly used biofluid for biomarker discovery. Although blood lipid metabolites are considered to be potential biomarker candidates, their fundamental properties are not well characterized. We aimed to (1 investigate the matrix type (serum vs. plasma that may be preferable for lipid biomarker exploration, (2 elucidate age- and gender-associated differences in lipid metabolite levels, and (3 examine the stability of lipid metabolites in matrix samples subjected to repeated freeze-thaw cycles. Using liquid chromatography-mass spectrometry, we performed lipidomic analyses for fasting plasma and serum samples for four groups (15 subjects/group of young and elderly (25-34 and 55-64 years old, respectively males and females and for an additional aliquot of samples from young males, which were subjected to repeated freeze-thaw cycles. Lysophosphatidylcholine and diacylglycerol levels were higher in serum than in plasma samples, suggesting that the clotting process influences serum lipid metabolite levels. Gender-associated differences highlighted that the levels of many sphingomyelin species were significantly higher in females than in males, irrespective of age and matrix (plasma and serum. Age-associated differences were more prominent in females than in males, and in both matrices, levels of many triacylglycerols were significantly higher in elderly females than in young females. Plasma and serum levels of most lipid metabolites were reduced by freeze-thawing. Our results indicate that plasma is an optimal matrix for exploring lipid biomarkers because it represents the original properties of an individual's blood sample. In addition, the levels of some blood lipid species of healthy adults showed gender- and age-associated differences; thus, this should be considered during biomarker exploration and its application in diagnostics. Our fundamental findings on sample selection and handling procedures for measuring blood lipid metabolites

  6. Comparison of the Usefulness of N-Terminal Pro-Brain Natriuretic Peptide to Other Serum Biomarkers as an Early Predictor of ST-Segment Recovery After Primary Percutaneous Coronary Intervention

    NARCIS (Netherlands)

    Verouden, Niels J. W.; Haeck, Joost D. E.; Kuijt, Wichert J.; van Geloven, Nan; Koch, Karel T.; Henriques, José P. S.; Baan, Jan; Vis, Marije M.; van Straalen, Jan P.; Fischer, Johan; Piek, Jan J.; Tijssen, Jan G. P.; de Winter, Robbert J.

    2010-01-01

    Data on the ability of serum biomarkers to predict microvascular obstruction by ST-segment recovery after primary percutaneous coronary intervention (PCI) is largely absent. Therefore, we determined the association between 5 serum biomarkers, obtained before emergency coronary angiography, and

  7. Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

    Directory of Open Access Journals (Sweden)

    Valeria Diaz-Rizo

    Full Text Available There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN.In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN. A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02, whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07. Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001, but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02. Instead, leptin was not associated with LN.These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

  8. Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

    Science.gov (United States)

    Diaz-Rizo, Valeria; Bonilla-Lara, David; Gonzalez-Lopez, Laura; Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S; Perez-Guerrero, Edsaul E; Rodriguez-Jimenez, N Alejandra; Saldaña-Cruz, A Miriam; Vazquez-Villegas, M Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario; Gamez-Nava, Jorge I

    2017-01-01

    There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

  9. Serum biomarkers for the diagnosis and monitoring of chronic recurrent multifocal osteomyelitis (CRMO).

    Science.gov (United States)

    Hofmann, Sigrun Renate; Kubasch, Anne Sophie; Range, Ursula; Laass, Martin Walther; Morbach, Henner; Girschick, Hermann Joseph; Hedrich, Christian Michael

    2016-06-01

    Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis, is an autoinflammatory bone disorder. A timely diagnosis and treatment initiation is complicated by the absence of widely accepted diagnostic criteria and an incomplete pathophysiological understanding. The aim of this study was to determine biomarkers for the diagnosis and follow-up of CRMO. Serum of 56 CRMO patients was collected at the time of diagnosis. As controls, sera from treatment-naïve age-matched patients with Crohn's disease (N = 62) or JIA (N = 28) as well as healthy individuals (N = 62) were collected. Multiplex analysis of 25 inflammation markers was performed. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests, canonical discriminant analysis, and mixed model variance analysis. Mostly monocyte-derived serum proteins were detectable and differed significantly between groups: IL-1RA, IL-2R, IL-6, IL-12, eotaxin, MCP-1, MIP-1b, RANTES. Multicomponent discriminant analysis allowed for the definition of algorithms differentiating between CRMO, Crohn's disease, and healthy controls. Persistently high levels of MCP-1, IL-12, sIL-2R correlated with incomplete remission in follow-up samples from CRMO patients. Discrimination algorithms allow differentiation between patients with CRMO or Crohn's disease, and healthy individuals. IL-12, MCP-1, and sIL-2R can act as markers for treatment response. Though confirmation of our findings in larger multiethnical cohorts is warranted, they may prove valuable to differentiate between otherwise healthy individuals or Crohn's disease patients with "bone pain" and CRMO patients. The elevation of mainly monocyte-derived pro-inflammatory serum proteins supports the hypothesis of pro-inflammatory monocyte/macrophages driving inflammation in CRMO.

  10. Serum big endothelin-1 as a biomarker in oral squamous cell carcinoma patients: an analytical study

    Directory of Open Access Journals (Sweden)

    Pritam Kumar MANKAPURE

    2015-10-01

    Full Text Available Detection of abnormally elevated levels of molecules in patients with oral cancer may be useful in early diagnosis. These markers can be included in current Histopathology grading and in TNM staging systems of Oral Squamous Cell Carcinoma (OSCC to make it more efficient. Several pro-angiogenic molecules have been assessed for the same reason. Endothelin-1 (ET-1 is a vasoactive peptide associated with the development and spread of many solid tumors, including Squamous Cell Carcinoma (SCC, but its utility in OSCC has not been confirmed.Objective This study aims to evaluate the role of the serum big ET-1 as a biomarker of OSCC, by correlating it with the clinical staging and the histopathological grading.Material and Methods Serum levels of big ET-1 measured by the sandwich Enzyme-Linked Immunosorbent Assay (ELISA in 40 OSCC cases were compared with the levels from the control group using independent t-test. Clinical stages and histopathological grades of OSCC cases were compared in relation to their mean levels of serum big ET-1, one using the Analysis of Variance (ANOVA test and the other the independent t-test, respectively. The significance of the mean difference between the groups was evaluated by Tukey’s multiple comparison test. All statistical analyses were performed on GraphPad statistical software version 5.0.Results By comparing the mean of the big ET-1 concentrations of cases and controls, the independent t-test revealed significant higher big ET-1 concentration of OSCC cases when compared to controls (p<0.0001. Tukey’s multiple comparison test also revealed statistically significant difference among all OSCC stages in relation to the mean levels of serum big ET-1. However, the mean of the big ET-1 concentrations of cases of grade I and of grade II did not differ statistically (p=0.729.Conclusion Serum big ET-1 levels may be useful as a diagnostic tool in OSCC and as an adjunct to OSCC staging. However, its use as a prognostic

  11. Profiling of circulating microRNAs for prostate cancer biomarker discovery

    DEFF Research Database (Denmark)

    Haldrup, Christa; Kosaka, Nobuyoshi; Ochiya, Takahiro

    2014-01-01

    biopsy, and better and less invasive tools for PC detection are needed. Furthermore, whereas aggressive PC should be treated immediately to prevent dissemination, indolent PC often does not progress and overtreatment should be avoided. Currently, the best predictors of aggressiveness are Gleason score...... and T-stage of the primary PC. Better tools to assess PC aggressiveness could aid in treatment decisions. Recently, circulating miRNAs have been suggested as potential new biomarkers for PC with diagnostic and prognostic potential. Here, to identify new serum miRNA biomarker candidates for PC, we...

  12. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus.

    Science.gov (United States)

    Ionescu, Catalina; Corbu, Catalina Gabriela; Tanase, Cristiana; Jonescu-Cuypers, Christian; Nicula, Cristina; Dascalescu, Dana; Cristea, Miruna; Voinea, Liliana-Mary

    2016-01-01

    Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus.

  13. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus

    Science.gov (United States)

    Jonescu-Cuypers, Christian; Nicula, Cristina; Voinea, Liliana-Mary

    2016-01-01

    Keratoconus is a degenerative disorder with progressive stromal thinning and transformation of the normal corneal architecture towards ectasia that results in decreased vision due to irregular astigmatism and irreversible tissue scarring. The pathogenesis of keratoconus still remains unclear. Hypotheses that this condition has an inflammatory etiopathogenetic component apart from the genetic and environmental factors are beginning to escalate in the research domain. This paper covers the most relevant and recent published papers regarding the biomarkers of inflammation, their signaling pathway, and the potentially new therapeutic options in keratoconus. PMID:27563164

  14. Preoperative serum lipid profile and outcome in nonmetastatic colorectal cancer.

    Science.gov (United States)

    Hong, Ting-Ting; Shen, Di; Chen, Xiao-Ping; Wu, Xiao-Hong; Hua, Dong

    2016-12-01

    A large portion of non-metastatic colorectal cancers (non-mCRCs) recur after curative surgery. In addition to the traditional tumor-related factors, host-related factors are also required to accurately predict prognosis. A few studies have shown an association between the serum lipid profile and the survival and treatment response of patients with colorectal cancer. We retrospectively evaluated the prognostic significance of the preoperative serum lipid profile [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] in patients with non-mCRC treated with curative surgery. The Spearman rank correlation test was used to analyze associations between lipid levels and categorical variables. Lipid levels were modeled as four equal-sized quartiles based on the distribution among the whole cohort. Kaplan-Meier curves were used to estimate survival probabilities, and the log-rank test was used to detect differences between them. Multivariate fractional polynomial (MFP) analysis was used to model any non-linear effects and avoid categorization. To evaluate the added prognostic value of lipids, the predictive power of two models (with and without lipids as covariates) was compared by using Harrell's C-statistic and the Akaike information criterion (AIC). A total of 266 patients with non-mCRC were enrolled in the present study. Spearman rank correlation test showed that TG levels inversely correlated with N stage (r = -0.20, P = 0.00) and Tumor-Node-Metastasis (TNM) stage (r = -0.19, P = 0.00). HDL-C levels positively correlated with perineural invasion (PNI) (r = 0.15, P = 0.02), and LDL-C levels inversely correlated with lymphovascular invasion (LVI) (r = -0.12, P = 0.04). None of the four lipids predicted overall survival (OS) in univariate or multivariate analyses adjusted for age, gender, T stage, N stage, TNM stage, histological grade, tumor deposits, LVI, PNI, and adjuvant treatment

  15. Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks

    Energy Technology Data Exchange (ETDEWEB)

    Fliniaux, Ophelie [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Gaillard, Gwenaelle [Biobanque de Picardie (France); Lion, Antoine [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Cailleu, Dominique [Batiment Serres-Transfert, rue de Mai/rue Dallery, Plateforme Analytique (France); Mesnard, Francois, E-mail: francois.mesnard@u-picardie.fr [University of Picardie Jules Verne, Laboratoire de Phytotechnologie EA 3900-BioPI (France); Betsou, Fotini [Integrated Biobank of Luxembourg (Luxembourg)

    2011-12-15

    A blood pre-centrifugation delay of 24 h at room temperature influenced the proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation delay of 24 h at 4 Degree-Sign C did not influence the spectroscopic profile as compared with 4 h delays at either room temperature or 4 Degree-Sign C. Five or ten serum freeze-thaw cycles also influenced the proton NMR spectroscopic profiles. Certain common in vitro preanalytical variations occurring in biobanks may impact the metabolic profile of human serum.

  16. Serum biomarkers of Burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses.

    Science.gov (United States)

    Glaros, Trevor G; Blancett, Candace D; Bell, Todd M; Natesan, Mohan; Ulrich, Robert G

    2015-01-01

    The bacterium Burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. Clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. However, progress in developing sensitive assays for monitoring B. mallei infection is hampered by a shortage of useful biomarkers. Reasoning that there should be a strong correlation between the proteomes of infected tissues and circulating serum, we employed imaging mass spectrometry (IMS) of thin-sectioned tissues from Chlorocebus aethiops (African green) monkeys infected with B. mallei to localize host and pathogen proteins that were associated with abscesses. Using laser-capture microdissection of specific regions identified by IMS and histology within the tissue sections, a more extensive proteomic analysis was performed by a technique that combined the physical separation capabilities of liquid chromatography (LC) with the sensitive mass analysis capabilities of mass spectrometry (LC-MS/MS). By examining standard formalin-fixed, paraffin-embedded tissue sections, this strategy resulted in the identification of several proteins that were associated with lung and skin abscesses, including the host protein calprotectin and the pathogen protein GroEL. Elevated levels of calprotectin detected by ELISA and antibody responses to GroEL, measured by a microarray of the bacterial proteome, were subsequently detected in the sera of C. aethiops, Macaca mulatta, and Macaca fascicularis primates infected with B. mallei. Our results demonstrate that a combination of multidimensional MS analysis of traditional histology specimens with high-content protein microarrays can be used to discover lead pairs of host-pathogen biomarkers of infection that are identifiable in biological fluids.

  17. Human Epididymis Protein 4: A Novel Serum Inflammatory Biomarker in Cystic Fibrosis.

    Science.gov (United States)

    Nagy, Béla; Nagy, Béla; Fila, Libor; Clarke, Luka A; Gönczy, Ferenc; Bede, Olga; Nagy, Dóra; Újhelyi, Rita; Szabó, Ágnes; Anghelyi, Andrea; Major, Miklós; Bene, Zsolt; Fejes, Zsolt; Antal-Szalmás, Péter; Bhattoa, Harjit Pal; Balla, György; Kappelmayer, János; Amaral, Margarida D; Macek, Milan; Balogh, István

    2016-09-01

    /bronchial epithelial cells compared with wild-type cells. HE4 serum levels positively correlate with the overall severity of CF and the degree of pulmonary dysfunction. HE4 may thus be used as a novel inflammatory biomarker and possibly also as a measure of treatment efficacy in CF lung disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  18. Analysis of four serum biomarkers in rheumatoid arthritis: association with extra articular manifestations in patients and arthralgia in relatives.

    Science.gov (United States)

    Nass, Flávia R; Skare, Thelma L; Goeldner, Isabela; Nisihara, Renato; Messias-Reason, Iara T; Utiyama, Shirley R R

    To evaluate the frequency of four serum biomarkers in RA patients and their relatives and identify possible associations with clinical findings of the disease. This was a transversal analytical study. Anti-cyclic citrullinated peptide (anti-CCP), anti-mutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in 210 RA patients, 198 relatives and 92 healthy controls from Southern Brazil. Clinical and demographic data were obtained through charts review and questionnaires. A higher positivity for all antibodies was observed in RA patients when compared to relatives and controls (p<0.0001). IgA-RF was more frequent in relatives compared to controls (14.6% vs. 5.4%, p=0.03, OR=2.98; 95% CI=1.11-7.98) whereas anti-CCP was the most common biomarker among RA patients (75.6%). Concomitant positivity for the four biomarkers was more common in patients (46.2%, p<0.0001). Relatives and controls were mostly positive for just one biomarker (20.2%, p<0.0001 and 15.2%, p=0.016, respectively). No association was observed between the number of positive biomarkers and age of disease onset, functional class or tobacco exposure. In seronegative patients predominate absence of extra articular manifestations (EAMs) (p=0.01; OR=3.25; 95% CI=1.16-10.66). Arthralgia was present in positive relatives, regardless the type of biomarker. A higher number of biomarkers was present in RA patients with EAMs. Positivity of biomarkers was related to arthralgia in relatives. These findings reinforce the link between distinct biomarkers and the pathophysiologic mechanisms of AR. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  19. Biomarker Profiles of Acute Heart Failure Patients With a Mid-Range Ejection Fraction

    NARCIS (Netherlands)

    Tromp, Jasper; Khan, Mohsin A. F.; Mentz, Robert J.; O'Connor, Christopher M.; Metra, Marco; Dittrich, Howard C.; Ponikowski, Piotr; Teerlink, John R.; Cotter, Gad; Davison, Beth; Cleland, John G. F.; Givertz, Michael M.; Bloomfield, Daniel M.; Van Veldhuisen, Dirk J.; Hillege, Hans L.; Voors, Adriaan A.; van der Meer, Peter

    OBJECTIVES In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart

  20. Effect of an exercise and dietary intervention on serum biomarkers in overweight and obese adults with osteoarthritis of the knee.

    Science.gov (United States)

    Chua, S D; Messier, S P; Legault, C; Lenz, M E; Thonar, E J-M A; Loeser, R F

    2008-09-01

    To determine the effects of exercise and weight loss interventions on serum levels of four biomarkers and to examine if changes in biomarker levels correlate with clinical outcome measures in obese and overweight adults with knee osteoarthritis (OA). Serum was obtained at baseline, 6 and 18 months from 193 participants in Arthritis, Diet and Activity Promotion Trial. This was a single-blind 18-month trial with subjects randomized to four groups: healthy-lifestyle (HL), diet (D), exercise (E) and diet plus exercise (D+E). Serum levels of cartilage oligomeric matrix protein (COMP), hyaluronan (HA), antigenic keratan sulfate (AgKS), and transforming growth factor-beta1 (TGF-beta1) were measured by enzyme linked immunosorbent assay. At baseline there were no significant differences in biomarker levels between intervention groups. When results for all the intervention groups were combined, the levels of HA were found to be negatively correlated with medial joint space width and positively correlated with Kellgren-Lawrence scores (K-L scores) while TGF-beta1 levels negatively correlated with K-L scores. When biomarker levels measured at 6 and 18 months were adjusted for baseline values, age, gender, and body mass index, weak but significant differences between intervention groups were present for mean levels of COMP and TGF-beta1. Furthermore, AgKS levels averaged over all groups tended to decrease over time. There were no significant associations of baseline biomarkers and the follow-up outcomes. Weak associations were noted between change in the biomarkers at 18 months and change in outcome measures that included change in weight with AgKS and COMP and change in Western Ontario and McMaster Universities Osteoarthritis Index pain with AgKS. Overall, the E and D interventions did not show a consistent effect on levels of potential OA biomarkers. The four biomarkers showed differences in correlations with outcome measures suggesting that they may measure different aspects

  1. MicroRNA let-7i is a promising serum biomarker for blast-induced traumatic brain injury.

    Science.gov (United States)

    Balakathiresan, Nagaraja; Bhomia, Manish; Chandran, Raghavendar; Chavko, Mikulas; McCarron, Richard M; Maheshwari, Radha K

    2012-05-01

    Blast-induced traumatic brain injury (TBI) is of significant concern in soldiers returning from the current conflicts in Iraq and Afghanistan. Incidents of TBI have increased significantly in the current conflicts compared to previous wars, and a majority of these injuries are caused by improvised explosive devices. Currently, no specific technique or biomarker is available for diagnosing TBI when no obvious clinical symptoms are present. Micro-RNAs are small RNA (~ 22nts) molecules that are expressed endogenously and play an important role in regulating gene expression. MicroRNAs have emerged as novel serum diagnostic biomarkers for various diseases. In this study, we studied the effect of blast overpressure injury on the microRNA signatures in the serum of rats. Rats were exposed to three serial 120-kPa blast overpressure exposures through a shockwave tube. Blood and cerebrospinal fluid were collected at various time points after injury, and microRNA modulation was analyzed using real-time PCR. Five microRNAs were significantly modulated in the serum samples of these animals at three time points post-injury. Further, we also found that the levels of microRNA let-7i are also elevated in cerebrospinal fluid post-blast wave exposure. The presence of microRNA in both serum and cerebrospinal fluid immediately after injury makes microRNA let-7i an ideal candidate for further studies of biomarkers in TBI.

  2. Human stem cell osteoblastogenesis mediated by novel glycogen synthase kinase 3 inhibitors induces bone formation and a unique bone turnover biomarker profile in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gilmour, Peter S., E-mail: Peter.Gilmour@astrazeneca.com [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); O' Shea, Patrick J.; Fagura, Malbinder [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Pilling, James E. [Discovery Sciences, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Sanganee, Hitesh [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Wada, Hiroki [R and I IMed, AstraZeneca R and D, Molndal (Sweden); Courtney, Paul F. [DMPK, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Kavanagh, Stefan; Hall, Peter A. [Safety Assessment, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom); Escott, K. Jane [New Opportunities Innovative Medicines group, AstraZeneca R and D, Alderley Park, Cheshire SK10 4TF (United Kingdom)

    2013-10-15

    Wnt activation by inhibiting glycogen synthase kinase 3 (GSK-3) causes bone anabolism in rodents making GSK-3 a potential therapeutic target for osteoporotic and osteolytic metastatic bone disease. To understand the wnt pathway related to human disease translation, the ability of 3 potent inhibitors of GSK-3 (AZD2858, AR79, AZ13282107) to 1) drive osteoblast differentiation and mineralisation using human adipose-derived stem cells (hADSC) in vitro; and 2) stimulate rat bone formation in vivo was investigated. Bone anabolism/resorption was determined using clinically relevant serum biomarkers as indicators of bone turnover and bone formation assessed in femurs by histopathology and pQCT/μCT imaging. GSK-3 inhibitors caused β-catenin stabilisation in human and rat mesenchymal stem cells, stimulated hADSC commitment towards osteoblasts and osteogenic mineralisation in vitro. AZD2858 produced time-dependent changes in serum bone turnover biomarkers and increased bone mass over 28 days exposure in rats. After 7 days, AZD2858, AR79 or AZ13282107 exposure increased the bone formation biomarker P1NP, and reduced the resorption biomarker TRAcP-5b, indicating increased bone anabolism and reduced resorption in rats. This biomarker profile was differentiated from anabolic agent PTH{sub 1–34} or the anti-resorptive Alendronate-induced changes. Increased bone formation in cortical and cancellous bone as assessed by femur histopathology supported biomarker changes. 14 day AR79 treatment increased bone mineral density and trabecular thickness, and decreased trabecular number and connectivity assessed by pQCT/μCT. GSK-3 inhibition caused hADSC osteoblastogenesis and mineralisation in vitro. Increased femur bone mass associated with changes in bone turnover biomarkers confirmed in vivo bone formation and indicated uncoupling of bone formation and resorption. - Highlights: • Wnt modulation with 3 novel GSK-3 inhibitors alters bone growth. • Human stem cell osteoblastogenesis

  3. Maternal serum glycosylated fibronectin as a point-of-care biomarker for assessment of preeclampsia.

    Science.gov (United States)

    Rasanen, Juha; Quinn, Matthew J; Laurie, Amber; Bean, Eric; Roberts, Charles T; Nagalla, Srinivasa R; Gravett, Michael G

    2015-01-01

    We assessed the association of glycosylated fibronectin (GlyFn) with preeclampsia and its performance in a point-of-care (POC) test. GlyFn, placental growth factor (PlGF), and soluble vascular endothelial growth factor receptor 1 (sFlt1) levels were determined in serum samples from 107 pregnant women. In all, 45 were normotensive and 62 were diagnosed with preeclampsia. The ability of GlyFn to assess preeclampsia status and relationships between GlyFn and maternal characteristics and pregnancy outcomes were analyzed. GlyFn serum levels in the first trimester were significantly higher in women with preeclampsia (P preeclampsia status, and the classification performance of these analytes represented by area under the receiver operating characteristic curve was 0.99, 0.96, 0.94, and 0.98, respectively, with 95% confidence intervals of 0.98-1.00, 0.89-1.00, 0.86-1.00, and 0.94-1.00, respectively. Increased GlyFn levels were significantly associated with gestational age at delivery (P preeclampsia was associated with a weekly change of 81.7 μg/mL (SE 94.1) vs 195.2 μg/mL (SE 88.2) for severe preeclampsia. The GlyFn POC demonstrated similar performance to a plate assay with an area under the receiver operating characteristic curve of 0.93 and 95% confidence interval of 0.85-1.00. GlyFn is a robust biomarker for monitoring of preeclampsia in both a standard and POC format, which supports its utility in diverse settings. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Delayed Imatinib Treatment for Acute Spinal Cord Injury: Functional Recovery and Serum Biomarkers

    Science.gov (United States)

    Finn, Anja; Hao, Jingxia; Wellfelt, Katrin; Josephson, Anna; Svensson, Camilla I.; Wiesenfeld-Hallin, Zsuzsanna; Eriksson, Ulf; Abrams, Mathew

    2015-01-01

    Abstract With no currently available drug treatment for spinal cord injury, there is a need for additional therapeutic candidates. We took the approach of repositioning existing pharmacological agents to serve as acute treatments for spinal cord injury and previously found imatinib to have positive effects on locomotor and bladder function in experimental spinal cord injury when administered immediately after the injury. However, for imatinib to have translational value, it needs to have sustained beneficial effects with delayed initiation of treatment, as well. Here, we show that imatinib improves hind limb locomotion and bladder recovery when initiation of treatment was delayed until 4 h after injury and that bladder function was improved with a delay of up to 24 h. The treatment did not induce hypersensitivity. Instead, imatinib-treated animals were generally less hypersensitive to either thermal or mechanical stimuli, compared with controls. In an effort to provide potential biomarkers, we found serum levels of three cytokines/chemokines—monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-3α, and keratinocyte chemoattractant/growth-regulated oncogene (interleukin 8)—to increase over time with imatinib treatment and to be significantly higher in injured imatinib-treated animals than in controls during the early treatment period. This correlated to macrophage activation and autofluorescence in lymphoid organs. At the site of injury in the spinal cord, macrophage activation was instead reduced by imatinib treatment. Our data strengthen the case for clinical trials of imatinib by showing that initiation of treatment can be delayed and by identifying serum cytokines that may serve as candidate markers of effective imatinib doses. PMID:25914996

  5. Chip-LC-MS for label-free profiling of human serum

    NARCIS (Netherlands)

    Horvatovich, Peter; Govorukhina, Natalia .; Reijmers, Theo H.; van der Zee, Ate G. J.; Suits, Frank; Bischoff, Rainer

    2007-01-01

    The discovery of biomarkers in easily accessible body fluids such as serum is one of the most challenging topics in proteomics requiring highly efficient separation and detection methodologies. Here, we present the application of a microfluidics-based LC-MS system (chip-LC-MS) to the label-free

  6. Serum miRNAs miR-206, 143-3p and 374b-5p as potential biomarkers for amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Waller, Rachel; Goodall, Emily F; Milo, Marta; Cooper-Knock, Jonathan; Da Costa, Marc; Hobson, Esther; Kazoka, Mbombe; Wollff, Helen; Heath, Paul R; Shaw, Pamela J; Kirby, Janine

    2017-07-01

    Amyotrophic lateral sclerosis (ALS) is a fatal, neurodegenerative condition characterized by loss of motor neurones and progressive muscle wasting. There is no diagnostic test for ALS therefore robust biomarkers would not only be valuable for diagnosis, but also for the classification of disease subtypes, monitoring responses to drugs and tracking disease progression. As regulators of gene expression, microRNAs (miRNAs) are increasingly used for diagnostic and prognostic purposes in various disease states with increasing exploration in neurodegenerative disorders. We hypothesize that circulating blood-based miRNAs will serve as biomarkers and use miRNA profiling to determine miRNA signatures from the serum of sporadic ALS patients compared to healthy controls and patients with diseases that mimic ALS. A number of differentially expressed miRNAs were identified in each set of patient comparisons. Validation in an additional patient cohort showed that miR-206 and miR-143-3p were increased and miR-374b-5p was decreased compared to controls. A continued change in miRNA expression persisted during disease progression indicating the potential use of these particular miRNAs as longitudinal biomarkers in ALS. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. The Utility of Serum IgG4 Concentrations as a Biomarker

    Science.gov (United States)

    Kawa, Shigeyuki; Ito, Tetsuya; Watanabe, Takayuki; Maruyama, Masahiro; Hamano, Hideaki; Maruyama, Masafumi; Muraki, Takashi; Arakura, Norikazu

    2012-01-01

    IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1) systemic involvement; (2) solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3) high serum IgG4 concentration >135 mg/dL; (4) abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5) a positive response to corticosteroid therapy; and (6) complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease. PMID:22536256

  8. The Utility of Serum IgG4 Concentrations as a Biomarker

    Directory of Open Access Journals (Sweden)

    Shigeyuki Kawa

    2012-01-01

    Full Text Available IgG4-related disease is a new disease entity involving IgG4 in its clinical presentation and having 6 characteristic features: (1 systemic involvement; (2 solitary or multiple lesions showing diffuse or localized swelling, masses, nodules, and/or wall thickening on imaging; (3 high serum IgG4 concentration >135 mg/dL; (4 abundant infiltration of lymphoplasmacytes and IgG4-bearing plasma cells; (5 a positive response to corticosteroid therapy; and (6 complications of other IgG4-related diseases. To date, most IgG4-related diseases have been recognized as extrapancreatic lesions of autoimmune pancreatitis. This paper will discuss the utility of IgG4 as a biomarker of IgG4-related diseases, including in the diagnosis of autoimmune pancreatitis and its differentiation from pancreatic cancer, in the prediction of relapse, in the long-term follow-up of patients with autoimmune pancreatitis and normal or elevated IgG4 concentrations, and in patients with autoimmune pancreatitis and extrapancreatic lesions, as well as the role of IgG4 in the pathogenesis of IgG4-related disease.

  9. Conjugated bile acids in gallbladder bile and serum as potential biomarkers for cholesterol polyps and adenomatous polyps.

    Science.gov (United States)

    Zhao, Mei-Fen; Huang, Peng; Ge, Chun-Lin; Sun, Tao; Ma, Zhi-Gang; Ye, Fei-Fei

    2016-02-28

    To identify conjugated bile acids in gallbladder bile and serum as possible biomarkers for cholesterol polyps (CPs) and adenomatous polyps (APs). Gallbladder bile samples and serum samples were collected from 18 patients with CPs (CP group), 9 patients with APs (AP group), and 20 patients with gallstones (control group) from March to November, 2013. High performance liquid chromatography (HPLC) assay with ultraviolent detection was used to detect the concentration of 8 conjugated bile acids (glycocholic acid, GCA; taurocholic acid, TCA; glycochenodeoxycholic acid, GCDCA; taurochenodeoxycholic acid, TCDCA; glycodeoxycholic acid, GDCA; taurodeoxycholic acid, TDCA; taurolithocholic acid, TLCA; tauroursodeoxycholic acid, TUDCA) in bile samples and serum samples. The diagnostic efficacy of serum GCA, GCDCA and TCDCA was evaluated. These 8 conjugated bile acids in gallbladder bile and serum were completely identified within 10 minutes with good linearity (correlation coefficient: R>0.9900; linearity range: 3.91-500 µg/mL). Among these conjugated bile acids, the levels of gallbladder bile GCDCA and TCDCA in the CP group were significantly higher than those in the AP group (p<0.05). Furthermore, serum GCDCA and TCDCA as well as GCA were significantly higher in the AP group than the CP group (p<0.05). Serum GCDCA alone (≤12 µg/mL) had relatively better diagnostic efficacy than the other conjugated bile acids. The levels of serum GCA, GCDCA and TCDCA may be valuable for differentiation of APs and CPs.

  10. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease.

    Science.gov (United States)

    Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Jewell, D E

    2014-01-01

    Symmetric dimethylarginine (SDMA) has been shown to be an accurate and precise biomarker for calculating estimated glomerular filtration rate (GFR) in humans, as well as a more sensitive biomarker than serum creatinine concentration (sCr) for assessing renal dysfunction. The purpose of this retrospective study was to report on the utility of measuring serum SDMA concentrations in cats for detection of chronic kidney disease (CKD) before diagnosis by conventional measurement of sCr. Chronic kidney disease cats (n = 21) included those persistently azotemic for ≥3 months (n = 15), nonazotemic cats with GFR >30% decreased from median GFR of normal cats (n = 4), and nonazotemic cats with calcium oxalate kidney stones (n = 2). Healthy geriatric cats (n = 21) were selected from the same colony. Symmetric dimethylarginine concentrations (liquid chromatography-mass spectroscopy) and sCr (enzymatic colorimetry) were determined retrospectively from historical data or banked serum samples in azotemic cats or at the time GFR (iohexol clearance) was measured in nonazotemic cats. Serum SDMA (r = -0.79) and sCr (r = -0.77) concentrations were significantly correlated to GFR (both P cats (mean, 17.0 months; range, 1.5-48 months). Serum SDMA had higher sensitivity (100%) compared with sCr (17%), but lower specificity (91% versus 100%) and positive predictive value (86% versus 100%). Using serum SDMA as a biomarker for CKD allows earlier detection of CKD in cats compared with sCr, which may be desirable for initiating renoprotective interventions that slow progression of CKD. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  11. [Effect of amygdalin on serum proteinic biomarker in pulmonary fibrosis of bleomycin-induced rat].

    Science.gov (United States)

    Du, Hai-Ke; Song, Fu-Cheng; Zhou, Xin; Li, He; Zhang, Jian-Peng

    2010-04-01

    To evaluate effect of amygdalin on expression of four biomarkers in the animal model of pulmonary fibrosis induced by bleomycin. Rats were given one dose (5 mg/kg) of bleomycin in bleomycin-treated groups, amygdalin-treated groups and saline in controls by intratracheal instillation exposed surgically. The amygdalin-treated groups rats were treated with intraperitoneal injection of amygdalin (15 mg x kg(-1) x day(-1)). The rats were sacrificed 7, 14 and 28 days after bleomycin administration. Polarized light microscopy and Image-Pro Plus detected I and III collagen expressed in Paraffin-embedded lung sections stained with Sirius red. Surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) with weak cationic proteinchip (CM10) detected differentially expressed proteins in the pooled serum samples of all groups. Consistent fibrotic responses were found in all bleomycin and amygdalin-tread groups. On the 7th, 14th and 28th day after bleomycin or saline instillation, four differentially expressed proteins were detected in the pooled serum of all groups rats, consisting of 4 proteins with mass/charge ratio of 3530.7, 7043.5, 8332.6 and 9068.0, respectively. Compared with control groups, protein peaks intensity ratio with mass/charge ratio of 3530.7 on 7, 28 d and 7043.5, 8332.6 and 9068.0 on 7, 14 and 28 d was > 2 in bleomycin-treated groups. Compared with amygdalin-treated groups, protein peaks intensity with mass/charge ratio of 3530.7 at 7, 14, 28 d had no change almost, but protein peaks intensity ratio with mass/charge ratio of 7043.5 at 7 d, 8332.6 on 28 d and 9068.0 on 14 d was > 2 in bleomycin-tread groups. All the four protein peaks intensity had no change almost at other point. Amygdalin may reduce the bleomycin-induced increase of differentially expressed protein peak intensities in rat serum.

  12. Serum exosomal protein profiling for the non-invasive detection of cardiac allograft rejection.

    Science.gov (United States)

    Kennel, Peter J; Saha, Amit; Maldonado, Dawn A; Givens, Raymond; Brunjes, Danielle L; Castillero, Estibaliz; Zhang, Xiaokan; Ji, Ruiping; Yahi, Alexandre; George, Isaac; Mancini, Donna M; Koller, Antonius; Fine, Barry; Zorn, Emmanuel; Colombo, Paolo C; Tatonetti, Nicholas; Chen, Emily I; Schulze, P Christian

    2017-07-19

    Exosomes are cell-derived circulating vesicles that play an important role in cell-cell communication. Exosomes are actively assembled and carry messenger RNAs, microRNAs and proteins. The "gold standard" for cardiac allograft surveillance is endomyocardial biopsy (EMB), an invasive technique with a distinct complication profile. The development of novel, non-invasive methods for the early diagnosis of allograft rejection is warranted. We hypothesized that the exosomal proteome is altered in acute rejection, allowing for a distinction between non-rejection and rejection episodes. Serum samples were collected from heart transplant (HTx) recipients with no rejection, acute cellular rejection (ACR) and antibody-mediated rejection (AMR). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of serum exosome was performed using a mass spectrometer (Orbitrap Fusion Tribrid). Principal component analysis (PCA) revealed a clustering of 3 groups: (1) control and heart failure (HF); (2) HTx without rejection; and (3) ACR and AMR. A total of 45 proteins were identified that could distinguish between groups (q < 0.05). Comparison of serum exosomal proteins from control, HF and non-rejection HTx revealed 17 differentially expressed proteins in at least 1 group (q < 0.05). Finally, comparisons of non-rejection HTx, ACR and AMR serum exosomes revealed 15 differentially expressed proteins in at least 1 group (q < 0.05). Of these 15 proteins, 8 proteins are known to play a role in the immune response. Of note, the majority of proteins identified were associated with complement activation, adaptive immunity such as immunoglobulin components and coagulation. Characterizing of circulating exosomal proteome in different cardiac disease states reveals unique protein expression patterns indicative of the respective pathologies. Our data suggest that HTx and allograft rejection alter the circulating exosomal protein content. Exosomal protein analysis could be a novel approach

  13. Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease.

    Science.gov (United States)

    Hokamp, J A; Cianciolo, R E; Boggess, M; Lees, G E; Benali, S L; Kovarsky, M; Nabity, M B

    2016-01-01

    Urine protein loss is common in dogs with chronic kidney disease (CKD). To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. One hunderd and eighty dogs with naturally occurring kidney disease. Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P dogs with proteinuric CKD and might predict specific disease types and survival. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  14. Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to Infliximab in Rheumatoid Arthritis: An Exploratory Study.

    Directory of Open Access Journals (Sweden)

    Ignacio Ortea

    Full Text Available Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05, representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40. This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023. On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and

  15. Femtomolar detection of a cancer biomarker protein in serum with ultralow background current by anodic stripping voltammetry.

    Science.gov (United States)

    Shiddiky, Muhammad J A; Kithva, Prakash H; Rauf, Sakandar; Trau, Matt

    2012-05-22

    An electrochemical immunosensor for the detection of a cancer biomarker protein in serum at femtomolar concentrations with ultralow background response has been developed, which consists of (i) a hydrophilic polyacrylic acid brush-modified indium tin oxide substrate as an antifouling substrate and (ii) a graphene-quantum dots-antibody 'bionanoconjugate' as a signal amplification label in voltammetric detection of targets in a glassy carbon electrode.

  16. SERUM LIPIDOMIC BIOMARKERS FROM PATIENTS WITH PROSTATE PATHOLOGY, IDENTIFIED BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED WITH MASS SPECTROMETRY

    OpenAIRE

    Gligor Andrei Lazar; Florina Romanciuc; Nicolae Crisan; Carmen Socaiu

    2016-01-01

    Introduction: Lipidomics can offer an instant picture of the lipophilic metabolites from tissues and biofluids and can indicate the evolution of different pathologies, such as hyperplasia or different types of cancers. Related to these pathologies, Prostate Serum Antigen (PSA), proved to have a low grade prediction for an accurate diagnosis. Meanwhile, untargeted or targeted metabolomics became a useful advanced technology to discover new biomarkers for a better diagnosis. Aims: To  reali...

  17. Detection of the Inflammation Biomarker C-Reactive Protein in Serum Samples: Towards an Optimal Biosensor Formula

    Directory of Open Access Journals (Sweden)

    Wellington M. Fakanya

    2014-10-01

    Full Text Available The development of an electrochemical immunosensor for the biomarker, C-reactive protein (CRP, is reported in this work. CRP has been used to assess inflammation and is also used in a multi-biomarker system as a predictive biomarker for cardiovascular disease risk. A gold-based working electrode sensor was developed, and the types of electrode printing inks and ink curing techniques were then optimized. The electrodes with the best performance parameters were then employed for the construction of an immunosensor for CRP by immobilizing anti-human CRP antibody on the working electrode surface. A sandwich enzyme-linked immunosorbent assay (ELISA was then constructed after sample addition by using anti-human CRP antibody labelled with horseradish peroxidase (HRP. The signal was generated by the addition of a mediator/substrate system comprised of 3,3,5',5'-Tetramethylbenzidine dihydrochloride (TMB and hydrogen peroxide (H2O2. Measurements were conducted using chronoamperometry at −200 mV against an integrated Ag/AgCl reference electrode. A CRP limit of detection (LOD of 2.2 ng·mL−1 was achieved in spiked serum samples, and performance agreement was obtained with reference to a commercial ELISA kit. The developed CRP immunosensor was able to detect a diagnostically relevant range of the biomarker in serum without the need for signal amplification using nanoparticles, paving the way for future development on a cardiac panel electrochemical point-of-care diagnostic device.

  18. A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

    Science.gov (United States)

    Parsons, Christine; Gorospe, Myriam; Ferrucci, Luigi; Gill, Thomas M.; Slack, Frank J.

    2016-01-01

    In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92. Numerous miRNAs showed significant changes in expression levels. At age 50, 24 miRNAs were significantly upregulated, and 73 were significantly downregulated in the long-lived subgroup (76-92 years) as compared with the short-lived subgroup (58-75 years). In long-lived participants, the most upregulated was miR-373-5p, while the most downregulated was miR-15b-5p. Longitudinally, significant Pearson correlations were observed between lifespan and expression of nine miRNAs (p valueaging-associated proteins, including PARP1, IGF1R, and IGF2R. We propose that the expression profiles of the six miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, and 1225-3p) may be useful biomarkers of aging. PMID:27824314

  19. Biomarkers of Exposure to Toxic Substances. Volume 5: Biomarker Pre-validation Studies Prevalidation of Urine and Serum Biomarkers Indicative of Subclinical Kidney Damage in a Nephrotoxin Model

    Science.gov (United States)

    2009-05-01

    component complex prevents its filtration from the kidney. However, once retinol is released, the apoRBP4 is quickly filtered out the kidney...bladder cancer (Malmström et al., 1993) and as a plasma biomarker for preeclampsia (Yasumizu et al., 1996) although a thorough interrogation as to its...332, 6163, Mar 1988 pp. 411-415. Yasumizu T, and Kato J, “Clinical evaluation of plasma fibronectin level as a biomarker of preeclampsia ,” The

  20. Metabolomic profiles as reliable biomarkers of dietary composition.

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    Esko, Tõnu; Hirschhorn, Joel N; Feldman, Henry A; Hsu, Yu-Han H; Deik, Amy A; Clish, Clary B; Ebbeling, Cara B; Ludwig, David S

    2017-03-01

    Background: Clinical nutrition research often lacks robust markers of compliance, complicating the interpretation of clinical trials and observational studies of free-living subjects.Objective: We aimed to examine metabolomics profiles in response to 3 diets that differed widely in macronutrient composition during a controlled feeding protocol.Design: Twenty-one adults with a high body mass index (in kg/m(2); mean ± SD: 34.4 ± 4.9) were given hypocaloric diets to promote weight loss corresponding to 10-15% of initial body weight. They were then studied during weight stability while consuming 3 test diets, each for a 4-wk period according to a crossover design: low fat (60% carbohydrate, 20% fat, 20% protein), low glycemic index (40% carbohydrate, 40% fat, 20% protein), or very-low carbohydrate (10% carbohydrate, 60% fat, 30% protein). Plasma samples were obtained at baseline and at the end of each 4-wk period in the fasting state for metabolomics analysis by using liquid chromatography-tandem mass spectrometry. Statistical analyses included adjustment for multiple comparisons.Results: Of 333 metabolites, we identified 152 whose concentrations differed for ≥1 diet compared with the others, including diacylglycerols and triacylglycerols, branched-chain amino acids, and markers reflecting metabolic status. Analysis of groups of related metabolites, with the use of either principal components or pathways, revealed coordinated metabolic changes affected by dietary composition, including pathways related to amino acid metabolism. We constructed a classifier using the metabolites that differed between diets and were able to correctly identify the test diet from metabolite profiles in 60 of 63 cases (>95% accuracy). Analyses also suggest differential effects by diet on numerous cardiometabolic disease risk factors.Conclusions: Metabolomic profiling may be used to assess compliance during clinical nutrition trials and the validity of dietary assessment in observational

  1. Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker

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    Emma Louise Beckett

    2015-12-01

    General significance: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.

  2. Evaluation of Individual and Combined Applications of Serum Biomarkers for Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

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    Bin Hu

    2013-12-01

    Full Text Available The clinical value of Serum alpha-fetoprotein (AFP to detect early hepatocellular carcinoma (HCC has been questioned due to its low sensitivity and specificity found in recent years. Other than AFP, several new serum biomarkers including the circulating AFP isoform AFP-L3, des-gamma-carboxy prothrombin (DCP and Golgi protein-73 (GP73 have been identified as useful HCC markers. In this investigation, we review the current knowledge about these HCC-related biomarkers, and sum up the results of our meta-analysis on studies that have addressed the utility of these biomarkers in early detection and prognostic prediction of HCC. A systematic search in PubMed, Web of Science, and the Cochrane Library was performed for articles published in English from 1999 to 2012, focusing on serum biomarkers for HCC detection. Data on sensitivity and specificity of tests were extracted from 40 articles that met the inclusion criteria, and the summary receiver operating characteristic curve (sROC was obtained. A meta-analysis was carried out in which the area under the curve (AUC for each biomarker or biomarker combinations (AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 was used to compare the diagnostic accuracy of different biomarker tests. The AUC of AFP, DCP, GP73, AFP-L3, AFP + DCP, AFP + AFP-L3, and AFP + GP73 are 0.835, 0.797, 0.914, 0.710, 0.874, 0.748, and 0.932 respectively. A combination of AFP + GP73 is superior to AFP in detecting HCC and differentiating HCC patients from non-HCC patients, and may prove to be a useful marker in the diagnosis and screening of HCC. In addition, the AUC of GP73, AFP + DCP and AFP + GP73 are better than that of AFP. The clinical value of GP73, AFP + DCP, or AFP + GP73 as serological markers for HCC diagnosis needs to be addressed further in future studies.

  3. Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased

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    Gonzales, Rachel M.; Daly, Don S.; Tan, Ruimin; Marks, Jeffrey R.; Zangar, Richard C.

    2011-07-01

    Background: Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods: A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

  4. Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy

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    Maria Bjerke

    2014-10-01

    Full Text Available Background: Small vessel disease (SVD represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD. Methods: CSF SVD-related biomarkers [neurofilament light (NF-L, myelin basic protein (MBP, soluble amyloid precursor protein-β (sAPPβ, matrix metalloproteinases (MMPs, and tissue inhibitor of metalloproteinase (TIMP] were analysed in 46 non-demented elderly with imaging findings of SVD. We assessed the relationship between the CSF biomarkers and white matter hyperintensity (WMH volume, diffusion-weighted imaging and atrophy as well as their association with neuropsychological profiles. Results: The WMH volume correlated with ventricular dilation, which was associated with executive function and speed and attention. Increased WMH and ventricular dilation were related to increased CSF levels of TIMP-1, NF-L and MBP and to decreased sAPPβ. A positive correlation was found between the CSF biomarker MMP-9 and WMH progression. Conclusions: The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration. CSF TIMP-1, NF-L, MBP and sAPPβ may function as biological markers of white matter damage.

  5. Influence of physical and emotional activity on the metabolic profile of blood serum of race horses

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    T. I. Bayeva

    2016-09-01

    Full Text Available In the article data are presented on dynamics of the level of indicators of metabolic profile of blood serum of race horses of the Ukrainian riding breed in the conditions of physical and emotional loading. Clinically healthy race horses were the object of  research. Blood was taken from the jugular vein to obtain serum and for further biochemical research. For the research 12 race horses from a training group were chosen. From time to time the animals took part in competitions; they were not specially used in races and were mostly used for the training of junior riders and sportsmen of different levels. Blood was taken in conditions of relative rest after ordinary training and after emotional stress during the entertainment performances when a large number of people were present and loud music was played. In the blood serum the following biochemical indicators were defined: whole protein, urea, creatinine, uric acid, total bilirubin and its fractions, glucose, cholestererol, triacylglycerol, calcium, ferrum, lactate, pyruvate, activity of the AlAT, SGOT, GGTP, LDH, an alkaline phosphatase – which makes it possible to determine reasonably accurately the adaptation potential of a horse under various types of loading. We established that during training and psychoemotional loading of racing horses of the training group of the Ukrainian riding breed, multidirectional changes in the level of biochemical indicators of blood serum occurred, which is evidence of stress in the metabolic processes in the animals’ organisms. Concentration of a biomarker of an oxidative stress, uric acid, increased after physical loading by 8.6%, and after emotional loading by 55.1%, which demonstrates that emotional stress had the more negative effect, indicating insufficient adaptation by the horses before demonstration performances. After physical loading, reaction of transamination in the horses’ liver cells intensified, and after emotional loading its intensity

  6. Identification of serum biomarkers for occupational medicamentosa-like dermatitis induced by trichloroethylene using mass spectrometry

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    Hong, Wen-Xu; Liu, Wei [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Zhang, Yanfang [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Tang, Haiyan [Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518001 (China); Zhou, Guifeng [Medical School of Hunan Normal University, Changsha 410006 (China); Huang, Xinfeng; Zhuang, Zhixiong [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Liu, Jianjun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Medical Key Laboratory of Guangdong Province, Medical Key Laboratory of Health Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China)

    2013-11-15

    Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become a serious occupational health hazard. In the present study, we collected fasting blood samples from patients with OMLDT (n = 18) and healthy volunteers (n = 33) to explore serum peptidome patterns. Peptides in sera were purified using weak cation exchange magnetic beads (MB-WCX), and analyzed by matrix-assisted laser desorption ionization time-of-flight-mass spectrometry (MALDI-TOF-MS) and ClinProTools bioinformatics software. The intensities of thirty protein/peptide peaks were significantly different between the healthy control and OMLDT patients. A pattern of three peaks (m/z 2106.3, 2134.5, and 3263.67) was selected for supervised neural network (SNN) model building to separate the OMLDT patients from the healthy controls with a sensitivity of 95.5% and a specificity of 73.8%. Furthermore, two peptide peaks of m/z 4091.61 and 4281.69 were identified as fragments of ATP-binding cassette transporter family A member 12 (ABCA12), and cationic trypsinogen (PRRS1), respectively. Our findings not only show that specific proteomic fingerprints in the sera of OMLDT patients can be served as a differentiated tool of OMLDT patients with high sensitivity and high specificity, but also reveal the novel correlation between OMLDT with ABC transports and PRRS1, which will be of potential value for clinical and mechanistic studies of OMLDT. - Highlights: • Identify 30 differential protein/peptide peaks between OMLDT and healthy control • The test sensitivity and test specificity were 95.5% and 73.8%, respectively. • ABCA12 and PRSS1 were identified as potential biomarkers in OMLDT patients.

  7. Evaluation of RANKL/OPG Serum Concentration Ratio as a New Biomarker for Coronary Artery Calcification: A Pilot Study

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    Amir Hooshang Mohammadpour

    2012-01-01

    Full Text Available Objective. There is a strong need for biomarkers to identify patients at risk for future cardiovascular events related with progressive atherosclerotic disease. Osteoprotegerin (OPG protects the skeleton from excessive bone resorption by binding to receptor activator of nuclear factor-κB ligand (RANKL and preventing it from binding to its receptor, receptor activator of nuclear factor-κB. However, conflicting results have been obtained about association of serum level of OPG or RANKL with coronary artery disease (CAD. Based on their role in inflammation and matrix degradation and the fact that atherosclerotic plaque formation is an inflammatory process, we hypothesized that RANKL : OPG ratio could be a better biomarker for CAD. Methods. In this cross-sectional study, the correlation between RANKL : OPG ratio serum concentration and coronary artery calcification (CAC in 50 patients with ischemic coronary disease has been investigated. We used ELISA method for measuring RANKL and OPG serum concentrations. Results. There was a significant correlation between RANKL : OPG serum concentration ratio and CAC in our study population (P=0.01. Conclusion. Our results suggested that RANKL : OPG ratio concentration has a potential of being used as a marker for coronary artery disease.

  8. Serum Ceramide Kinase as a Biomarker of Cognitive Functions, and the Effect of Using Two Slimming Dietary Therapies in Obese Middle Aged Females.

    Science.gov (United States)

    Moaty, Maha I A; Fouad, Suzanne; El Shebini, Salwa M; Kazem, Yusr M I; Ahmed, Nihad H; Mohamed, Magda S; Hussein, Ahmed M S; Arafa, Atiat M; Hanna, Laila M; Tapozada, Salwa T

    2015-03-15

    Highlighting the impact of obesity on mental and cognitive functions using serum ceramide kinase enzyme concentration as a biomarker for cognitive evaluation in the middle aged females, and also targeting to control the obesity and simultaneously postponing the deterioration of the cognitive functions, by implementing two slimming dietary therapies each incorporating different functional ingredients known to boost cognition. Ninety six obese middle aged females, divided into two groups volunteered to follow a low caloric balanced diet combined with two bread supplements composed essentially of barley flour and wheat germ mixed with either 5% turmeric, group (A); or with 5% ginger, group (B) for 4 weeks, phase (1); to be followed by the hypocaloric diet alone for another 4 weeks, phase (2). By the end of phase (1), the biochemical analysis showed a positive response of the levels of C-peptide and modified homeostatic model assessment of insulin resistance; also increased levels of the serum ceramide kinase enzyme, coupled with improved cognitive functions tests. Improvement of the relevant metabolic profile, fasting blood glucose, blood pressure and the anthropometric measurements was detected. Using dietary therapy supported by special formulas which contain active ingredients succeeded in reducing weight and improving both the metabolic profile and the cognitive functions.

  9. Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model.

    Science.gov (United States)

    Schwarzinger, Michaël; Sagaon-Teyssier, Luis; Cabaret, Odile; Bretagne, Stéphane; Cordonnier, Catherine

    2013-01-01

    The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking. We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3)- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus. The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010), independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53). The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.

  10. Performance of serum biomarkers for the early detection of invasive aspergillosis in febrile, neutropenic patients: a multi-state model.

    Directory of Open Access Journals (Sweden)

    Michaël Schwarzinger

    Full Text Available The performance of serum biomarkers for the early detection of invasive aspergillosis expectedly depends on the timing of test results relative to the empirical administration of antifungal therapy during neutropenia, although a dynamic evaluation framework is lacking.We developed a multi-state model describing simultaneously the likelihood of empirical antifungal therapy and the risk of invasive aspergillosis during neutropenia. We evaluated whether the first positive test result with a biomarker is an independent predictor of invasive aspergillosis when both diagnostic information used to treat and risk factors of developing invasive aspergillosis are taken into account over time. We applied the multi-state model to a homogeneous cohort of 185 high-risk patients with acute myeloid leukemia. Patients were prospectively screened for galactomannan antigenemia twice a week for immediate treatment decision; 2,214 serum samples were collected on the same days and blindly assessed for (1->3- β-D-glucan antigenemia and a quantitative PCR assay targeting a mitochondrial locus.The usual evaluation framework of biomarker performance was unable to distinguish clinical benefits of β-glucan or PCR assays. The multi-state model evidenced that the risk of invasive aspergillosis is a complex time function of neutropenia duration and risk management. The quantitative PCR assay accelerated the early detection of invasive aspergillosis (P = .010, independently of other diagnostic information used to treat, while β-glucan assay did not (P = .53.The performance of serum biomarkers for the early detection of invasive aspergillosis is better apprehended by the evaluation of time-varying predictors in a multi-state model. Our results provide strong rationale for prospective studies testing a preemptive antifungal therapy, guided by clinical, radiological, and bi-weekly blood screening with galactomannan antigenemia and a standardized quantitative PCR assay.

  11. Development of a serum biomarker panel predicting recurrence in stage I non-small cell lung cancer patients.

    Science.gov (United States)

    Rinewalt, Daniel; Shersher, David D; Daly, Shaun; Fhied, Cristina; Basu, Sanjib; Mahon, Brett; Hong, Edward; Chmielewski, Gary; Liptay, Michael J; Borgia, Jeffrey A

    2012-12-01

    Molecular diagnostics capable of prognosticating disease recurrence in stage I non-small cell lung cancer (NSCLC) patients have implications for improving survival. The objective of the present study was to develop a multianalyte serum algorithm predictive of disease recurrence in stage I NSCLC patients. The Luminex immunobead platform was used to evaluate 43 biomarkers against 79 patients with resectable NSCLC, with the following cohorts represented: stage I (T(1)-T(2)N(0)M(0)) NSCLC without recurrence (n = 37), stage I (T(1)-T(2)N(0)M(0)) NSCLC with recurrence (n = 15), and node-positive (T(1)-T(2)N(1)-N(2)M(0)) NSCLC (n = 27). Peripheral blood was collected before surgery, with all patients undergoing anatomic resection. Univariate statistical methods (receiver operating characteristics curves and log-rank test) were used to evaluate each biomarker with respect to recurrence and outcome. Multivariate statistical methods were used to develop a prognostic classification panel for disease recurrence. No relationship was found between recurrence and age, gender, smoking history, or histologic type. Analysis for all stage I patients revealed 28 biomarkers significant for recurrence. Of these, the log-rank test identified 10 biomarkers that were strongly (P predicted recurrence in 77% of stage I patients tested, with a sensitivity of 74% and specificity of 79%. We report the development of a serum biomarker algorithm capable of preoperatively predicting disease recurrence in stage I NSCLC patients. Refinement of this panel might stratify patients for adjuvant therapy or aggressive recurrence monitoring to improve survival. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  12. Influence of racing on the serum concentrations of acute-phase proteins and bone metabolism biomarkers in racing greyhounds.

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    Tharwat, M; Al-Sobayil, F; Buczinski, S

    2014-11-01

    This study was designed to evaluate the influence of racing on the serum concentrations of the acute-phase proteins (APPs) C-reactive protein (CRP), haptoglobin (Hp) and serum amyloid A (SAA) in 32 endurance-racing greyhounds. The study also aimed to investigate the effect of a 7 km race on the bone biomarkers osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP) and pyridinoline cross-links (PYD). Total white blood cell (WBC) count, and the serum concentrations of cortisol, tumour necrosis factor-α (TNF-α), vitamin D and testosterone were also determined. Blood samples were collected 24 h prior to (T0) and within 2 h of completion of the race (T1). Compared to baseline values, WBC count did not change significantly (P = 0.2300), serum cortisol, Hp and SAA increased, while TNF-α and CRP decreased (P race serum concentrations of OC and PYD (P = 0.9500 and P = 0.2600, respectively), but serum b-ALP increased significantly (P = 0.0004). Serum concentrations of vitamin D and testosterone increased after racing (P = 0.0100 and P race stimulated an acute-phase response, demonstrated by significant increases in the serum concentrations Hp and SAA in racing greyhounds. Increased serum b-ALP post-race probably indicates a change in bone metabolism and deserves further study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease

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    Stewart Stephen

    2009-08-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC. Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. Methods 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1 pre-cirrhotic NAFLD (2 cirrhotic NAFLD and (3 cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Results Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L. By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. Conclusion This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.

  14. Effect of continuous positive airway pressure and upper airway surgery on exhaled breath condensate and serum biomarkers in patients with sleep apnea.

    Science.gov (United States)

    Lloberes, Patricia; Sánchez-Vidaurre, Sara; Ferré, Àlex; Cruz, María Jesús; Lorente, Juan; Sampol, Gabriel; Morell, Ferran; Muñoz, Xavier

    2014-10-01

    Studies on inflammation biomarkers in serum and in exhaled breath condensate (EBC) in obstructive sleep apnea (OSA) have shown conflicting results. The objective of this study is to assess EBC and serum biomarkers in OSA patients at baseline and after continuous positive airway pressure (CPAP) or upper airway surgery (UAS). Nine OSA patients referred for UAS were matched for anthropometric characteristics and apnea-hypopnea index with 20 patients receiving CPAP. pH, nitrite (NO2(-)), nitrate and interleukin 6 in EBC and NO2(-), nitrate, leukotriene B4 and interleukin 6 in serum were determined. EBC and serum samples were collected at baseline and 3 months after CPAP or UAS. Patients' mean body mass index was 30 (range 24.9-40) kg/m(2). EBC biomarker levels at baseline were within normal range and did not differ significantly after CPAP or UAS. No significant changes were observed in the serum concentration of the biomarkers determined after CPAP but the serum concentration of NO2(-) increased significantly at 3 months after UAS (P=.0078). In mildly obese OSA patients, EBC biomarkers of inflammation or oxidative stress were normal at baseline and remained unchanged 3 months after UAS or CPAP. Although UAS was not effective in terms of reducing OSA severity, it was associated with an increase in serum NO2(-). Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  15. Nutrition and inflammation serum biomarkers are associated with 12-week mortality among malnourished adults initiating antiretroviral therapy in Zambia.

    Science.gov (United States)

    Koethe, John R; Blevins, Meridith; Nyirenda, Christopher; Kabagambe, Edmond K; Shepherd, Bryan E; Wester, C William; Zulu, Isaac; Chiasera, Janelle M; Mulenga, Lloyd B; Mwango, Albert; Heimburger, Douglas C

    2011-04-10

    A low body mass index (BMI) at antiretroviral therapy (ART) initiation is a strong predictor of mortality among HIV-infected adults in resource-constrained settings. The relationship between nutrition and inflammation-related serum biomarkers and early treatment outcomes (e.g., less than 90 days) in this population is not well described. An observational cohort of 142 HIV-infected adults in Lusaka, Zambia, with BMI under 16 kg/m2 or CD4+ lymphocyte counts of less than 50 cells/mm3, or both, was followed prospectively during the first 12 weeks of ART. Baseline and serial post-treatment phosphate, albumin, ferritin and highly sensitive C-reactive protein (hsCRP) serum levels were measured. The primary outcome was mortality. Lower baseline phosphate and albumin serum levels, and higher ferritin and hsCRP, were significantly associated with mortality prior to 12 weeks (pART-associated mortality in sub-Saharan Africa. The time-dependent interval change in albumin was associated with mortality after adjusting for the baseline value (AHR 0.62 [0.43, 0.89] per 5 g/L increase), but changes in the other biomarkers were not. The predictive value of serum biomarkers for early mortality in a cohort of adults with malnutrition and advanced HIV in a resource-constrained setting was primarily driven by pre-treatment values, rather than post-ART changes. Interventions to promote earlier HIV diagnosis and treatment, address nutritional deficiencies, and identify the etiologies of increased systemic inflammation may improve ART outcomes in this vulnerable population.

  16. Effect of Mud-Bath Therapy on Serum Biomarkers in Patients with Knee Osteoarthritis: Results from a Randomized Controlled Trial.

    Science.gov (United States)

    Pascarelli, Nicola A; Cheleschi, Sara; Bacaro, Giovanni; Guidelli, Giacomo M; Galeazzi, Mauro; Fioravanti, Antonella

    2016-01-01

    Balneotherapy is one of the most commonly used non-pharmacological approaches for osteoarthritis (OA). Recent data indicate that some biomarkers could be useful to predict OA progression and to assess therapeutic response. To evaluate the effects of mud-bath therapy on serum biomarkers in patients with knee OA. The study group comprised 103 patients with primary symptomatic bilateral knee OA who were randomly assigned to receive a cycle of mud-bath therapy over a period of 2 weeks or to continue their standard therapy alone. Clinical and biochemical parameters were assessed at baseline and after 2 weeks. Clinical assessments included global pain score on a visual analogue scale (VAS) and the Western Ontario and McMaster Universities Index (WOMAC) subscores for knee OA. Cartilage oligomeric matrix protein (COMP), C-terminal cross-linked telopeptide type II collagen (CTX-II), myeloperoxidase (MPO) and high sensitivity C-reactive protein (hsCRP) serum levels were assessed by ELISA. At the end of mud-bath therapy we observed a statistically significant improvement in VAS and WOMAC subscores. Serum levels of COMP, MPO and hsCRP did not show any significant modification in either group, while a significant increase (P mud-bath group after the treatment. A cycle of mud-bath therapy added to the usual treatment had a beneficial effect on pain and function in patients with knee OA. The evaluation of serum biomarkers showed a significant increase of CTX-II only, perhaps due to an increase of cartilage turnover induced by thermal stress.

  17. Lysyl Oxidase as a Serum Biomarker of Liver Fibrosis in Patients with Severe Obesity and Obstructive Sleep Apnea

    Science.gov (United States)

    Mesarwi, Omar A.; Shin, Mi-Kyung; Drager, Luciano F.; Bevans-Fonti, Shannon; Jun, Jonathan C.; Putcha, Nirupama; Torbenson, Michael S.; Pedrosa, Rodrigo P.; Lorenzi-Filho, Geraldo; Steele, Kimberley E.; Schweitzer, Michael A.; Magnuson, Thomas H.; Lidor, Anne O.; Schwartz, Alan R.; Polotsky, Vsevolod Y.

    2015-01-01

    Study Objectives: Obstructive sleep apnea (OSA) is associated with the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that the hypoxia of OSA increases hepatic production of lysyl oxidase (LOX), an enzyme that cross-links collagen, and that LOX may serve as a biomarker of hepatic fibrosis. Design: Thirty-five patients with severe obesity underwent liver biopsy, polysomnography, and serum LOX testing. A separate group with severe OSA had serum LOX measured before and after 3 mo of CPAP or no therapy, as did age-matched controls. LOX expression and secretion were measured in mouse hepatocytes following exposure to hypoxia. Setting: The Johns Hopkins Bayview Sleep Disorders Center, and the Hypertension Unit of the Heart Institute at the University of São Paulo Medical School. Measurements and Results: In the bariatric cohort, the apnea-hypopnea index was higher in patients with hepatic fibrosis than in those without fibrosis (42.7 ± 30.2 events/h, versus 16.2 ± 15.5 events/h; P = 0.002), as was serum LOX (84.64 ± 29.71 ng/mL, versus 45.46 ± 17.16 ng/mL; P lysyl oxidase (LOX) levels. LOX may serve as a biomarker of liver fibrosis in patients with severe obesity and nonalcoholic fatty liver disease. Citation: Mesarwi OA, Shin MK, Drager LF, Bevans-Fonti S, Jun JC, Putcha N, Torbenson MS, Pedrosa RP, Lorenzi-Filho G, Steele KE, Schweitzer MA, Magnuson TH, Lidor AO, Schwartz AR, Polotsky VY. Lysyl oxidase as a serum biomarker of liver fibrosis in patients with severe obesity and obstructive sleep apnea. SLEEP 2015;38(10):1583–1591. PMID:26085300

  18. NanoString expression profiling identifies candidate biomarkers of RAD001 response in metastatic gastric cancer.

    Science.gov (United States)

    Das, Kakoli; Chan, Xiu Bin; Epstein, David; Teh, Bin Tean; Kim, Kyoung-Mee; Kim, Seung Tae; Park, Se Hoon; Kang, Won Ki; Rozen, Steve; Lee, Jeeyun; Tan, Patrick

    2016-01-01

    Gene expression profiling has contributed greatly to cancer research. However, expression-driven biomarker discovery in metastatic gastric cancer (mGC) remains unclear. A gene expression profile predicting RAD001 response in refractory GC was explored in this study. Total RNA isolated from 54 tumour specimens from patients with mGC, prior to RAD001 treatment, was analysed via the NanoString nCounter gene expression assay. This assay targeted 477 genes representing 10 different GC-related oncogenic signalling and molecular subtype-specific expression signatures. Gene expression profiles were correlated with patient clinicopathological variables. NanoString data confirmed similar gene expression profiles previously identified by microarray analysis. Signature I with 3 GC subtypes (mesenchymal, metabolic and proliferative) showed approximately 90% concordance where the mesenchymal and proliferative subtypes were significantly associated with signet ring cell carcinoma and the WHO classified tubular adenocarcinoma GC, respectively (p=0.042). Single-gene-level correlations with patient clinicopathological variables showed strong associations between FHL1 expression (mesenchymal subtype) and signet ring cell carcinoma, and NEK2 , OIP5 , PRC1 , TPX2 expression (proliferative subtype) with tubular adenocarcinoma (adjusted pNanoString nCounter gene expression profiling. Additionally, BRCA2 and MMP9 expression are potential predictive biomarkers for good response in RAD001-treated mGC.

  19. Comparison of GC-MS and GC×GC-MS in the analysis of human serum samples for biomarker discovery.

    Science.gov (United States)

    Winnike, Jason H; Wei, Xiaoli; Knagge, Kevin J; Colman, Steven D; Gregory, Simon G; Zhang, Xiang

    2015-04-03

    We compared the performance of gas chromatography time-of-flight mass spectrometry (GC-MS) and comprehensive two-dimensional gas chromatography mass spectrometry (GC×GC-MS) for metabolite biomarker discovery. Metabolite extracts from 109 human serum samples were analyzed on both platforms with a pooled serum sample analyzed after every 9 biological samples for the purpose of quality control (QC). The experimental data derived from the pooled QC samples showed that the GC×GC-MS platform detected about three times as many peaks as the GC-MS platform at a signal-to-noise ratio SNR ≥ 50, and three times the number of metabolites were identified by mass spectrum matching with a spectral similarity score Rsim ≥ 600. Twenty-three metabolites had statistically significant abundance changes between the patient samples and the control samples in the GC-MS data set while 34 metabolites in the GC×GC-MS data set showed statistically significant differences. Among these two groups of metabolite biomarkers, nine metabolites were detected in both the GC-MS and GC×GC-MS data sets with the same direction and similar magnitude of abundance changes between the control and patient sample groups. Manual verification indicated that the difference in the number of the biomarkers discovered using these two platforms was mainly due to the limited resolution of chromatographic peaks by the GC-MS platform, which can result in severe peak overlap making subsequent spectrum deconvolution for metabolite identification and quantification difficult.

  20. Haematological and Serum Biochemical Profile of the Blue Crab ...

    African Journals Online (AJOL)

    Haematology and serum biochemistry of the crab, Callinectes amnicola from Epe and Lagos Lagoon in southwest Nigeria were investigated from March –August, 2013. Haemocyte samples were analyzed for haematological and biochemical parameters. The Total Haemocyte count (THC) of C. amnicola from Epe and ...

  1. Weight reduction with improvement of serum lipid profile and ratios ...

    African Journals Online (AJOL)

    Development of novel natural dietary adjunct/agent with significant therapeutic effects on metabolic disease conditions such as obesity and heart disease raises concern in recent times. We studied chronic toxicity of the combined active ingredients present in the sesame leaves and their interaction on the fasting serum lipid ...

  2. [Use of serum protein profiling for early diagnosis of gastric cancer].

    Science.gov (United States)

    Zheng, Zhi-guo; Xu, Shen-hua; Xu, Qi; Zhu, Chi-hong; Yu, Chuan-ding

    2010-10-01

    To identify serum biomarkers associated with early gastric cancer. Serum proteins or peptides were purified with weak cation exchange magnetic beads in 433 patients with gastric cancer and 120 healthy subjects. Distinct peaks were selected using Biomarker Wizard software. The area under receiver operating characteristic curve(AUC) was generated to analyze discrimination capability of peaks between gastric cancers and health people. Thirteen distinct peaks were identified between 42 gastric cancer and 42 health people matched by age and gender(P<0.001). There were 5 peaks (2745, 2768, 6629, 3402, and 6436 m/z) with AUC greater than 0.8. Peak of 6629 m/z was identified to be transthyretin. The sensitivity and specificity of 6629 m/z were 65.5% and 92.0%. The sensitivity of 6629 m/z was 59.4% in I(A gastric cancer. Transthyretin precursor may be of value in the early diagnosis of gastric cancer.

  3. Exploration of Serum Proteomic Profiling and Diagnostic Model That Differentiate Crohn's Disease and Intestinal Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Fenming Zhang

    Full Text Available To explore the diagnostic models of Crohn's disease (CD, Intestinal tuberculosis (ITB and the differential diagnostic model between CD and ITB by analyzing serum proteome profiles.Serum proteome profiles from 30 CD patients, 21 ITB patients and 30 healthy controls (HCs were analyzed by using weak cationic magnetic beads combined with MALDI-TOF-MS technique to detect the differentially expressed proteins of serum samples. Three groups were made and compared accordingly: group of CD patients and HCs, group of ITB patients and HCs, group of CD patients and ITB patients. Wilcoxon rank sum test was used to screen the ten most differentiated protein peaks (P < 0.05. Genetic algorithm combining with support vector machine (SVM was utilized to establish the optimal diagnostic models for CD, ITB and the optimal differential diagnostic model between CD and ITB. The predictive effects of these models were evaluated by Leave one out (LOO cross validation method.There were 236 protein peaks differently expressed between group of CD patients and HCs, 305 protein peaks differently expressed between group of ITB patients and HCs, 332 protein peaks differently expressed between group of CD patients and ITB patients. Ten most differentially expressed peaks were screened out between three groups respectively (P < 0.05 to establish diagnostic models and differential diagnostic model. A diagnostic model comprising of four protein peaks (M/Z 4964, 3029, 2833, 2900 can well distinguish CD patients and HCs, with a specificity and sensitivity of 96.7% and 96.7% respectively. A diagnostic model comprising four protein peaks (M/Z 3030, 2105, 2545, 4210 can well distinguish ITB patients and HCs, with a specificity and sensitivity of 93.3% and 95.2% respectively. A differential diagnostic model comprising three potential biomarkers protein peaks (M/Z 4267, 4223, 1541 can well distinguish CD patients and ITB patients, with a specificity and sensitivity of 76.2% and 80

  4. Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth.

    Science.gov (United States)

    Summanen, Milla; Seikku, Laura; Rahkonen, Petri; Stefanovic, Vedran; Teramo, Kari; Andersson, Sture; Kaila, Kai; Rahkonen, Leena

    2017-01-01

    Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH Copeptin, S100B, and erythropoietin levels in umbilical artery samples were measured by immunoassays. Copeptin correlated in the entire study population more strongly with umbilical artery base excess than S100B and erythropoietin, and only copeptin correlated with arterial pH. Furthermore, only copeptin levels were significantly higher in cases of birth asphyxia, and in vaginally born neonates they were found to increase as a function of labor duration. Copeptin was elevated in neonates born via vacuum extraction, whereas erythropoietin levels showed a slight increase after emergency cesarean section. In this study population, S100B and erythropoietin were not valid biomarkers of birth asphyxia. In contrast, our work suggests that copeptin has high potential to become a routinely used biomarker for acute birth asphyxia and neonatal distress. © 2017 S. Karger AG, Basel.

  5. Classification of genes and putative biomarker identification using distribution metrics on expression profiles.

    Directory of Open Access Journals (Sweden)

    Hung-Chung Huang

    Full Text Available BACKGROUND: Identification of genes with switch-like properties will facilitate discovery of regulatory mechanisms that underlie these properties, and will provide knowledge for the appropriate application of Boolean networks in gene regulatory models. As switch-like behavior is likely associated with tissue-specific expression, these gene products are expected to be plausible candidates as tissue-specific biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: In a systematic classification of genes and search for biomarkers, gene expression profiles (GEPs of more than 16,000 genes from 2,145 mouse array samples were analyzed. Four distribution metrics (mean, standard deviation, kurtosis and skewness were used to classify GEPs into four categories: predominantly-off, predominantly-on, graded (rheostatic, and switch-like genes. The arrays under study were also grouped and examined by tissue type. For example, arrays were categorized as 'brain group' and 'non-brain group'; the Kolmogorov-Smirnov distance and Pearson correlation coefficient were then used to compare GEPs between brain and non-brain for each gene. We were thus able to identify tissue-specific biomarker candidate genes. CONCLUSIONS/SIGNIFICANCE: The methodology employed here may be used to facilitate disease-specific biomarker discovery.

  6. Profiles of Biomarkers of Excess Alcohol Consumption in Patients Undergoing Total Hip Replacement: Correlation with Function

    Directory of Open Access Journals (Sweden)

    Paul J. Jenkins

    2011-01-01

    Full Text Available Aims. Patients who misuse alcohol may be at increased risk of surgical complications and poorer function following hip replacement. Identification and intervention may lead to harm reduction and improve the outcomes of surgery. The aim of this study was to determine the prevalence of biomarker elevation in patients undergoing hip replacement and to investigate any correlation with functional scores and complications. Methods. We performed a retrospective study that examined the profile of biomarkers of alcohol misuse in 1049 patients undergoing hip replacement. Results. Gamma-glutamyltransferase was elevated in 150 (17.6%, and mean corpuscular volume was elevated in 23 (4%. At one year general physical health was poorer where there was elevation of γGT, and the mental health and hip function was poorer with elevation of MCV. There were no differences in complications. Discussion. Raised biomarkers can alert clinicians to potential problems. They also provide an opportunity to perform further investigation and offer intervention. Future research should focus on the use in orthopaedic practice of validated screening questionnaires and more sensitive biomarkers of alcohol misuse. Conclusion. This study demonstrates a potential substantial proportion of unrecognised alcohol misuse that is associated with poorer functional scores in patients after total hip replacement.

  7. An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Szederjesi Janos

    2015-10-01

    Full Text Available Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR, urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.

  8. iTRAQ-Based Proteomics Identification of Serum Biomarkers of Two Chronic Hepatitis B Subtypes Diagnosed by Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Jiankun Yang

    2016-01-01

    Full Text Available Background. Chronic infection with hepatitis B virus (HBV is a leading cause of cirrhosis and hepatocellular carcinoma. By traditional Chinese medicine (TCM pattern classification, damp heat stasis in the middle-jiao (DHSM and liver Qi stagnation and spleen deficiency (LSSD are two most common subtypes of CHB. Results. In this study, we employed iTRAQ proteomics technology to identify potential serum protein biomarkers in 30 LSSD-CHB and 30 DHSM-CHB patients. Of the total 842 detected proteins, 273 and 345 were differentially expressed in LSSD-CHB and DHSM-CHB patients compared to healthy controls, respectively. LSSD-CHB and DHSM-CHB shared 142 upregulated and 84 downregulated proteins, of which several proteins have been reported to be candidate biomarkers, including immunoglobulin (Ig related proteins, complement components, apolipoproteins, heat shock proteins, insulin-like growth factor binding protein, and alpha-2-macroglobulin. In addition, we identified that proteins might be potential biomarkers to distinguish LSSD-CHB from DHSM-CHB, such as A0A0A0MS51_HUMAN (gelsolin, PON3_HUMAN, Q96K68_HUMAN, and TRPM8_HUMAN that were differentially expressed exclusively in LSSD-CHB patients and A0A087WT59_HUMAN (transthyretin, ITIH1_HUMAN, TSP1_HUMAN, CO5_HUMAN, and ALBU_HUMAN that were differentially expressed specifically in DHSM-CHB patients. Conclusion. This is the first time to report serum proteins in CHB subtype patients. Our findings provide potential biomarkers can be used for LSSD-CHB and DHSM-CHB.

  9. Defining the purity of exosomes required for diagnostic profiling of small RNA suitable for biomarker discovery.

    Science.gov (United States)

    Quek, Camelia; Bellingham, Shayne A; Jung, Chol-Hee; Scicluna, Benjamin J; Shambrook, Mitch C; Sharples, Robyn A; Cheng, Lesley; Hill, Andrew F

    2017-02-01

    Small non-coding RNAs (ncRNA), including microRNAs (miRNA), enclosed in exosomes are being utilised for biomarker discovery in disease. Two common exosome isolation methods involve differential ultracentrifugation or differential ultracentrifugation coupled with Optiprep gradient fractionation. Generally, the incorporation of an Optiprep gradient provides better separation and increased purity of exosomes. The question of whether increased purity of exosomes is required for small ncRNA profiling, particularly in diagnostic and biomarker purposes, has not been addressed and highly debated. Utilizing an established neuronal cell system, we used next-generation sequencing to comprehensively profile ncRNA in cells and exosomes isolated by these 2 isolation methods. By comparing ncRNA content in exosomes from these two methods, we found that exosomes from both isolation methods were enriched with miRNAs and contained a diverse range of rRNA, small nuclear RNA, small nucleolar RNA and piwi-interacting RNA as compared with their cellular counterparts. Additionally, tRNA fragments (30-55 nucleotides in length) were identified in exosomes and may act as potential modulators for repressing protein translation. Overall, the outcome of this study confirms that ultracentrifugation-based method as a feasible approach to identify ncRNA biomarkers in exosomes.

  10. Quantitative lateral flow strip assays as User-Friendly Tools To Detect Biomarker Profiles For Leprosy

    Science.gov (United States)

    van Hooij, Anouk; Tjon Kon Fat, Elisa M.; Richardus, Renate; van den Eeden, Susan J. F.; Wilson, Louis; de Dood, Claudia J.; Faber, Roel; Alam, Korshed; Richardus, Jan Hendrik; Corstjens, Paul L. A. M.; Geluk, Annemieke

    2016-01-01

    Leprosy is a debilitating, infectious disease caused by Mycobacterium leprae. Despite the availability of multidrug therapy, transmission is unremitting. Thus, early identification of M. leprae infection is essential to reduce transmission. The immune response to M. leprae is determined by host genetics, resulting in paucibacillary (PB) and multibacillary (MB) leprosy associated with dominant cellular or humoral immunity, respectively. This spectral pathology of leprosy compels detection of immunity to M. leprae to be based on multiple, diverse biomarkers. In this study we have applied quantitative user friendly lateral flow assays (LFAs) for four immune markers (anti-PGL-I antibodies, IL-10, CCL4 and IP-10) for whole blood samples from a longitudinal BCG vaccination field-trial in Bangladesh. Different biomarker profiles, in contrast to single markers, distinguished M. leprae infected from non-infected test groups, patients from household contacts (HHC) and endemic controls (EC), or MB from PB patients. The test protocol presented in this study merging detection of innate, adaptive cellular as well as humoral immunity, thus provides a convenient tool to measure specific biomarker profiles for M. leprae infection and leprosy utilizing a field-friendly technology. PMID:27682181

  11. Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Matilde Cirnigliaro

    2017-08-01

    Full Text Available Given its prevalence and social impact, Autism Spectrum Disorder (ASD is drawing much interest. Molecular basis of ASD is heterogeneous and only partially known. Many factors, including disorders comorbid with ASD, like TS (Tourette Syndrome, complicate ASD behavior-based diagnosis and make it vulnerable to bias. To further investigate ASD etiology and to identify potential biomarkers to support its precise diagnosis, we used TaqMan Low Density Array technology to profile serum miRNAs from ASD, TS, and TS+ASD patients, and unaffected controls (NCs. Through validation assays in 30 ASD, 24 TS, and 25 TS+ASD patients and 25 NCs, we demonstrated that miR-140-3p is upregulated in ASD vs.: NC, TS, and TS+ASD (Tukey's test, p-values = 0.03, = 0.01, < 0.0001, respectively. ΔCt values for miR-140-3p and YGTSS (Yale Global Tic Severity Scale scores are positively correlated (Spearman r = 0.33; Benjamini-Hochberg p = 0.008 and show a linear relationship (p = 0.002. Network functional analysis showed that nodes controlled by miR-140-3p, especially CD38 and NRIP1 which are its validated targets, are involved in processes convergingly dysregulated in ASD, such as synaptic plasticity, immune response, and chromatin binding. Biomarker analysis proved that serum miR-140-3p can discriminate among: (1 ASD and NC (Area under the ROC curve, AUC: 0.70; sensitivity: 63.33%; specificity: 68%; (2 ASD and TS (AUC: 0.72; sensitivity: 66.66%; specificity: 70.83%; (3 ASD and TS+ASD (AUC: 0.78; sensitivity: 73.33%; specificity: 76%. Characterization of miR-140-3p network would contribute to further clarify ASD etiology. Serum miR-140-3p could represent a potential non-invasive biomarker for ASD, easy to test through liquid biopsy.

  12. Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles.

    Science.gov (United States)

    Wang, Wei; Yang, Gen-Jin; Zhang, Ju; Chen, Chen; Jia, Zhen-Yu; Li, Jia; Xu, Wei-Dong

    2016-10-22

    they were also probably associated with immune regulation. Our work demonstrates that the potential biomarkers that were identified appeared to have diagnostic value for AS and deserve to be further investigated. In addition, this work also suggests that the metabolomic profiling approach is a promising screening tool for the diagnosis of patients with AS.

  13. Metabolic profiling of an Echinostoma caproni infection in the mouse for biomarker discovery.

    Directory of Open Access Journals (Sweden)

    Jasmina Saric

    Full Text Available BACKGROUND: Metabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states. The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse, and to compare the biomarkers extracted from different biofluids (plasma, stool, and urine in terms of characterizing acute and chronic stages of this intestinal fluke infection. METHODOLOGY/PRINCIPAL FINDINGS: Twelve female NMRI mice were infected with 30 E. caproni metacercariae each. Plasma, stool, and urine samples were collected at 7 time points up to day 33 post-infection. Samples were also obtained from non-infected control mice at the same time points and measured using (1H nuclear magnetic resonance (NMR spectroscopy. Spectral data were subjected to multivariate statistical analyses. In plasma and urine, an altered metabolic profile was already evident 1 day post-infection, characterized by reduced levels of plasma choline, acetate, formate, and lactate, coupled with increased levels of plasma glucose, and relatively lower concentrations of urinary creatine. The main changes in the urine metabolic profile started at day 8 post-infection, characterized by increased relative concentrations of trimethylamine and phenylacetylglycine and lower levels of 2-ketoisocaproate and showed differentiation over the course of the infection. CONCLUSION/SIGNIFICANCE: The current investigation is part of a broader NMR-based metabonomics profiling strategy and confirms the utility of this approach for biomarker discovery. In the case of E. caproni, a diagnosis based on all three biofluids would deliver the most comprehensive fingerprint of an infection. For practical purposes, however, future diagnosis might aim at a single biofluid, in which case urine would be chosen for further investigation, based on quantity of biomarkers, ease of sampling, and the degree of differentiation from the non

  14. Validating Serum S100B and Neuron-Specific Enolase as Biomarkers for the Human Brain – A Combined Serum, Gene Expression and MRI Study

    Science.gov (United States)

    Streitbürger, Daniel-Paolo; Arelin, Katrin; Kratzsch, Jürgen; Thiery, Joachim; Steiner, Johann; Villringer, Arno

    2012-01-01

    Introduction Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. Methods We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T1-weighted/diffusion tensor imaging) and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. Results We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity – the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. Conclusion Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results open a new perspective

  15. Validating serum S100B and neuron-specific enolase as biomarkers for the human brain - a combined serum, gene expression and MRI study.

    Directory of Open Access Journals (Sweden)

    Daniel-Paolo Streitbürger

    Full Text Available INTRODUCTION: Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. METHODS: We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T(1-weighted/diffusion tensor imaging and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. RESULTS: We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity - the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. CONCLUSION: Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results

  16. Endometrial cancer risk prediction including serum-based biomarkers : results from the EPIC cohort

    NARCIS (Netherlands)

    Fortner, Renée T.; Hüsing, Anika; Kühn, Tilman; Konar, Meric; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Boutron-Ruault, Marie Christine; Severi, Gianluca; Fournier, Agnès; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vasiliki; Orfanos, Philippos; Masala, Giovanna; Agnoli, Claudia; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Bueno-de-Mesquita, H. Bas|info:eu-repo/dai/nl/06929528X; Peeters, Petra H M|info:eu-repo/dai/nl/074099655; Weiderpass, Elisabete; Gram, Inger T.; Gavrilyuk, Oxana; Quirós, J. Ramón; Maria Huerta, José; Ardanaz, Eva; Larrañaga, Nerea; Lujan-Barroso, Leila; Sánchez-Cantalejo, Emilio; Butt, Salma Tunå; Borgquist, Signe; Idahl, Annika; Lundin, Eva; Khaw, Kay Tee; Allen, Naomi E.; Rinaldi, Sabina; Dossus, Laure; Gunter, Marc; Merritt, Melissa A.; Tzoulaki, Ioanna; Riboli, Elio; Kaaks, Rudolf

    2017-01-01

    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested

  17. Serum and Bronchoalveolar Lavage Fluid Endothelin‐1 Concentrations as Diagnostic Biomarkers of Canine Idiopathic Pulmonary Fibrosis

    National Research Council Canada - National Science Library

    Krafft, E; Heikkilä, H.P; Jespers, P; Peeters, D; Day, M.J; Rajamäki, M.M; Mc Entee, K; Clercx, C

    2011-01-01

    Background: Diagnosis of canine idiopathic pulmonary fibrosis (IPF) is challenging. Endothelin‐1 (ET1) is a biomarker of IPF in humans, but whether ET1 can detect and differentiate IPF from other canine respiratory diseases is unknown...

  18. Discovery of coding genetic variants influencing diabetes-related serum biomarkers and their impact on risk of type 2 diabetes

    DEFF Research Database (Denmark)

    Ahluwalia, Tarun Veer Singh; Allin, Kristine Højgaard; Sandholt, Camilla Helene

    2015-01-01

    CONTEXT: Type 2 diabetes (T2D) prevalence is spiraling globally, and knowledge of its pathophysiological signatures is crucial for a better understanding and treatment of the disease. OBJECTIVE: We aimed to discover underlying coding genetic variants influencing fasting serum levels of nine...... biomarkers associated with T2D: adiponectin, C-reactive protein, ferritin, heat shock 70-kDa protein 1B, IGF binding protein 1 and IGF binding protein 2, IL-18, IL-2 receptor-α, and leptin. DESIGN AND PARTICIPANTS: A population-based sample of 6215 adult Danes was genotyped for 16 340 coding single...

  19. Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy.

    Science.gov (United States)

    Campion, Carole G; Sanchez-Ferras, Oraly; Batchu, Sri N

    2017-01-01

    Diabetic nephropathy (DN) is a progressive kidney disease caused by alterations in kidney architecture and function, and constitutes one of the leading causes of end-stage renal disease (ESRD). The purpose of this review is to summarize the state of the art of the DN-biomarker field with a focus on the new strategies that enhance the sensitivity of biomarkers to predict patients who will develop DN or are at risk of progressing to ESRD. In this review, we provide a description of the pathophysiology of DN and propose a panel of novel putative biomarkers associated with DN pathophysiology that have been increasingly investigated for diagnosis, to predict disease progression or to provide efficient personal treatment. We performed a review of the literature with PubMed and Google Scholar to collect baseline data about the pathophysiology of DN and biomarkers associated. We focused our research on new and emerging biomarkers of DN. In this review, we summarized the critical signaling pathways and biological processes involved in DN and highlighted the pathogenic mediators of this disease. We next proposed a large review of the major advances that have been made in identifying new biomarkers which are more sensitive and reliable compared with currently used biomarkers. This includes information about emergent biomarkers such as functional noncoding RNAs, microRNAs, long noncoding RNAs, exosomes, and microparticles. Despite intensive strategies and constant investigation, no current single treatment has been able to reverse or at least mitigate the progression of DN, or reduce the morbidity and mortality associated with this disease. Major difficulties probably come from the renal disease being heterogeneous among the patients. Expanding the proteomics screening, including oxidative stress and inflammatory markers, along with metabolomics approaches may further improve the prognostic value and help in identifying the patients with diabetes who are at high risk of

  20. Impact of urbanisation on Serum lipid profiles -the thusa survey ...

    African Journals Online (AJOL)

    Objective. To examine the impact of urbanisation on lipid profiles of black South Africans, stratified for HIV status. Design. Cross-sectional population-based survey. Setting. North West province of South Africa. Subjects. A representative sample of 1854 apparently healthy volunteers aged ≥ 15 years, was recruited from 37 ...

  1. Correlation between serum lipid profile with anthropometric and ...

    African Journals Online (AJOL)

    Background: The problem of dyslipidemia is high in patients with diabetes mellitus. There is ample evidence that abnormalities in lipid metabolism are important risk factors for increased incidence of diabetes associated complications. The most important risk indicators for these complications are lipid profile abnormalities.

  2. Changes in Serum Electrolytes and Lipid Profile in Diabetes ...

    African Journals Online (AJOL)

    Background: Measurement of blood electrolytes level and lipid profile usually give good indications of the disease progression in a number of non communicable diseases. Objective: To investigate the effect of diabetes on electrolyte and lipid status of male and female diabetics in Freetown, Sierra Leone. Subjects and ...

  3. Serum lipids profile of untreated hypertensive patients in Port ...

    African Journals Online (AJOL)

    Background: Hypertension is the commonest non-communicable disease with variable prevalence rates in different parts of the world. Dyslipidaemia is associated with and predisposes to hypertension and hence increases the risk of cardiovascular disease. Aim: To determine the lipid profile in newly diagnosed ...

  4. Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome

    Science.gov (United States)

    2014-01-01

    Background The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Methods Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Results Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Conclusion Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment

  5. Serum proteomic analysis identifies sex-specific differences in lipid metabolism and inflammation profiles in adults diagnosed with Asperger syndrome.

    Science.gov (United States)

    Steeb, Hannah; Ramsey, Jordan M; Guest, Paul C; Stocki, Pawel; Cooper, Jason D; Rahmoune, Hassan; Ingudomnukul, Erin; Auyeung, Bonnie; Ruta, Liliana; Baron-Cohen, Simon; Bahn, Sabine

    2014-01-27

    The higher prevalence of Asperger Syndrome (AS) and other autism spectrum conditions in males has been known for many years. However, recent multiplex immunoassay profiling studies have shown that males and females with AS have distinct proteomic changes in serum. Here, we analysed sera from adults diagnosed with AS (males = 14, females = 16) and controls (males = 13, females = 16) not on medication at the time of sample collection, using a combination of multiplex immunoassay and shotgun label-free liquid chromatography mass spectrometry (LC-MSE). The main objective was to identify sex-specific serum protein changes associated with AS. Multiplex immunoassay profiling led to identification of 16 proteins that were significantly altered in AS individuals in a sex-specific manner. Three of these proteins were altered in females (ADIPO, IgA, APOA1), seven were changed in males (BMP6, CTGF, ICAM1, IL-12p70, IL-16, TF, TNF-alpha) and six were changed in both sexes but in opposite directions (CHGA, EPO, IL-3, TENA, PAP, SHBG). Shotgun LC-MSE profiling led to identification of 13 serum proteins which had significant sex-specific changes in the AS group and, of these, 12 were altered in females (APOC2, APOE, ARMC3, CLC4K, FETUB, GLCE, MRRP1, PTPA, RN149, TLE1, TRIPB, ZC3HE) and one protein was altered in males (RGPD4). The free androgen index in females with AS showed an increased ratio of 1.63 compared to controls. Taken together, the serum multiplex immunoassay and shotgun LC-MSE profiling results indicate that adult females with AS had alterations in proteins involved mostly in lipid transport and metabolism pathways, while adult males with AS showed changes predominantly in inflammation signalling. These results provide further evidence that the search for biomarkers or novel drug targets in AS may require stratification into male and female subgroups, and could lead to the development of novel targeted treatment approaches.

  6. Maternal Serum Macrophage Inhibitory Cytokine-1 as a Biomarker for Ectopic Pregnancy in Women with a Pregnancy of Unknown Location.

    Directory of Open Access Journals (Sweden)

    Monika M Skubisz

    Full Text Available Ectopic pregnancy (EP occurs in 1-2% of pregnancies, but is over-represented as a leading cause of maternal death in early pregnancy. It remains a challenge to diagnose early and accurately. Women often present in early pregnancy with a 'pregnancy of unknown location' (PUL and the diagnosis and exclusion of EP is difficult due to a lack of reliable biomarkers. A serum biomarker able to clearly distinguish between EP and other pregnancy outcomes would greatly assist clinicians in diagnosing and safely managing PULs. This study evaluates the ability of maternal serum macrophage inhibitory cytokine-1 (MIC-1 levels to differentiate between EP and other pregnancy outcomes in women with a PUL.Sera were collected from 120 women with a PUL at first clinical presentation and assayed for MIC-1 by ELISA. Results were classified according to ultimate pregnancy outcome and the discriminatory ability of MIC-1 to diagnose EP was assessed.Serum MIC-1 levels were lower in women with histologically confirmed (definite EP (dEP (median 552 ng/mL; interquartile range (IQR 414-693 ng/mL compared to women with definite viable intra-uterine pregnancies (dVIUPs (722 ng/mL; IQR 412-1122 ng/mL, and higher when compared to women with definite non-viable intra-uterine pregnancies (dNVIUPs (465 ng/mL; IQR 341-675 ng/mL. MIC-1 levels were significantly higher in women with dEP compared to women whose PULs resolved without medical intervention (srPUL (401 ng/mL; IQR 315-475 ng/mL (p1000 ng/mL.Serum MIC-1 levels in PUL were not able to categorically diagnose EP, however, MIC-1 could distinguish women with an EP that required medical intervention and those women whose PULs spontaneously resolved. A single serum MIC-1 measurement also excluded EP at levels above 1000 ng/mL. MIC-1 may play a role in the development of a combined assay of biomarkers for the diagnosis of EP.

  7. Association Between Chlorinated Pesticides in the Serum of Prepubertal Russian Boys and Longitudinal Biomarkers of Metabolic Function

    Science.gov (United States)

    Burns, Jane S.; Williams, Paige L.; Korrick, Susan A.; Hauser, Russ; Sergeyev, Oleg; Revich, Boris; Lam, Thuy; Lee, Mary M.

    2014-01-01

    Organochlorine pesticides (OCPs) have been linked to adult metabolic disorders; however, few studies have examined these associations in childhood. We prospectively evaluated the associations of baseline serum OCPs (hexachlorobenzene, β-hexachlorocyclohexane, and p,p′-dichlorodiphenyldichloroethylene) in Russian boys with subsequent repeated measurements of serum glucose, insulin, lipids, leptin, and calculated homeostatic model assessment of insulin resistance (IR). During 2003–2005, we enrolled 499 boys aged 8–9 years in a prospective cohort; 318 had baseline serum OCPs and serum biomarkers measured at ages 10–13 years. Multivariable generalized estimating equation and mediation regression models were used to examine associations and direct and indirect (via body mass index (BMI) (weight (kg)/height (m)2)) effects of prepubertal OCP tertiles and quintiles with biomarkers. In multivariable models, higher p,p′-dichlorodiphenyldichloroethylene (quintile 5 vs. quintile 1) was associated with lower leptin, with relative mean decreases of 61.8% (95% confidence interval: 48.4%, 71.7%) in models unadjusted for BMI and 22.2% (95% confidence interval: 7.1%, 34.9%) in models adjusted for BMI; the direct effect of p,p′-dichlorodiphenyldichloroethylene on leptin accounted for 27% of the total effect. IR prevalence was 6.6% at ages 12–13 years. Higher hexachlorobenzene (tertile 3 vs. tertile 1) was associated with higher odds of IR in models adjusted for BMI (odds ratio = 4.37, 95% confidence interval: 1.44, 13.28). These results suggest that childhood OCPs may be associated with IR and lower leptin. PMID:25255811

  8. A serum microRNA panel as potential biomarkers for hepatocellular carcinoma related with hepatitis B virus.

    Directory of Open Access Journals (Sweden)

    Youwen Tan

    Full Text Available The identification of new high-sensitivity and high-specificity markers for HCC are essential. We aimed to identify serum microRNAs (miRNAs as biomarkers to be used in diagnosing hepatitis B virus (HBV -related hepatocellular carcinoma (HCC.We investigated serum miRNA expression in (261 HCC patients, 233 cirrhosis patients, and 173 healthy controls, recruited between August 2010 and June 2013. An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR was used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 357 and then validated using an independent cohort (n = 241. The area under the receiver operating characteristic curve (AUC was used to evaluate the accuracy of the use of the biomarkers for disease diagnosis.We identified 8 miRNAs (hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-26a-5p and constructed an miRNA set that provided high diagnostic accuracy for HCC (AUC = 0.887 and 0.879 for training and validation sets, respectively. The miRNAs could also be used to differentiate HCC patients from healthy (AUC = 0.893 and cirrhosis (AUC = 0.892 patients.We identified a serum of miRNA panel that has considerable clinical value in HCC diagnosis.

  9. Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression.

    Science.gov (United States)

    Kurosaki, Akira; Hasegawa, Kosei; Kato, Tomomi; Abe, Kenji; Hanaoka, Tatsuya; Miyara, Akiko; O'Shannessy, Daniel J; Somers, Elizabeth B; Yasuda, Masanori; Sekino, Tetsuo; Fujiwara, Keiichi

    2016-04-15

    Folate receptor alpha (FRA) is a GPI-anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression-free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA-targeted therapy. © 2015 UICC.

  10. Lysyl Oxidase as a Serum Biomarker of Liver Fibrosis in Patients with Severe Obesity and Obstructive Sleep Apnea.

    Science.gov (United States)

    Mesarwi, Omar A; Shin, Mi-Kyung; Drager, Luciano F; Bevans-Fonti, Shannon; Jun, Jonathan C; Putcha, Nirupama; Torbenson, Michael S; Pedrosa, Rodrigo P; Lorenzi-Filho, Geraldo; Steele, Kimberley E; Schweitzer, Michael A; Magnuson, Thomas H; Lidor, Anne O; Schwartz, Alan R; Polotsky, Vsevolod Y

    2015-10-01

    Obstructive sleep apnea (OSA) is associated with the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that the hypoxia of OSA increases hepatic production of lysyl oxidase (LOX), an enzyme that cross-links collagen, and that LOX may serve as a biomarker of hepatic fibrosis. Thirty-five patients with severe obesity underwent liver biopsy, polysomnography, and serum LOX testing. A separate group with severe OSA had serum LOX measured before and after 3 mo of CPAP or no therapy, as did age-matched controls. LOX expression and secretion were measured in mouse hepatocytes following exposure to hypoxia. The Johns Hopkins Bayview Sleep Disorders Center, and the Hypertension Unit of the Heart Institute at the University of São Paulo Medical School. In the bariatric cohort, the apnea-hypopnea index was higher in patients with hepatic fibrosis than in those without fibrosis (42.7 ± 30.2 events/h, versus 16.2 ± 15.5 events/h; P = 0.002), as was serum LOX (84.64 ± 29.71 ng/mL, versus 45.46 ± 17.16 ng/mL; P sleep clinic sample, patients with severe OSA had higher baseline LOX than healthy controls (70.75 ng/mL versus 52.36 ng/mL, P = 0.046), and serum LOX decreased in patients with OSA on CPAP (mean decrease 20.49 ng/mL) but not in untreated patients (mean decrease 0.19 ng/mL). Hypoxic mouse hepatocytes demonstrated 5.9-fold increased LOX transcription (P = 0.046), and enhanced LOX protein secretion. The hypoxic stress of obstructive sleep apnea may increase circulating lysyl oxidase (LOX) levels. LOX may serve as a biomarker of liver fibrosis in patients with severe obesity and nonalcoholic fatty liver disease. © 2015 Associated Professional Sleep Societies, LLC.

  11. Profiling of microRNAs in tumor interstitial fluid of breast tumors - a novel resource to identify biomarkers for prognostic classification and detection of cancer.

    Science.gov (United States)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel; Wielenga, Vera Timmermans; Talman, Maj-Lis Møller; Brunner, Nils; Sandhu, Vandana; Børresen-Dale, Anne-Lise; Gromova, Irina; Haakensen, Vilde D

    2017-02-01

    It has been hypothesized based on accumulated data that a class of small noncoding RNAs, termed microRNAs, are key factors in intercellular communication. Here, microRNAs present in interstitial breast tumor fluids have been analyzed to identify relevant markers for a diagnosis of breast cancer and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266 microRNAs were present at higher level in the TIF samples as compared to normal counterparts. Sixty-one of these microRNAs were present in > 75% of the serum samples and were subsequently tested in a validation set. Seven of the 61 microRNAs were associated with poor survival, while 23 were associated with the presence of immune cells and adipocytes. To our knowledge, these data demonstrate for the first time that profiling of microRNAs in TIF can identify novel biomarkers for the prognostic classification and detection of breast cancer. In addition, the present findings demonstrate that microRNAs may represent the cross-talk that occurs between tumor cells and their surrounding stroma. © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  12. [Application of SELDI-TOF serum proteome profiling in cervical squamous cell carcinoma].

    Science.gov (United States)

    Xia, Ting; Zheng, Zhi-Guo; Gao, Yun; Mou, Han-Zhou; Xu, Shen-Hua; Zhang, Ping; Zhu, Jian-Qing

    2008-03-01

    Up to now, there is no valid biomarker in early diagnosis of cervical cancer. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) is a new technique used to identify biomarkers for cancers. This study was to screen new biomarkers and build diagnostic models for early diagnosis of cervical cancer by SELDI-TOF-MS. SELDI-TOF-MS was used to detect the serum proteomic patterns of 91 patients with early stage cervical squamous cell carcinoma, 15 patients with cervical intraepithelial neoplasia III (CIN III), and 55 healthy women (control). The serum proteomic spectra were generated on weak cation exchange (WCX2) chips. Differences in protein peaks were analyzed using Biomarker Wizard software. The diagnostic model was built by Biomarker Patterns software and further valuated by a large-scale blind test. A total of 122 protein peaks were detected at the molecular range of 1.5 to 20 ku, among which 19 ones were significantly different between invasive cervical squamous cell carcinomas and controls (P<0.001). A diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z was established. Its specificity was 83.78% (31/37) and its sensitivity was 97.29% (36/37). A sensitivity of 94.44% (51/54) and a specificity of 94.44% (17/18) in a large-scale blind test were obtained. The diagnostic model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z can discriminate cervical cancer patients from healthy women.

  13. Utility of the Blood for Gene Expression Profiling and Biomarker Discovery in Chronic Fatigue Syndrome

    Directory of Open Access Journals (Sweden)

    Suzanne D. Vernon

    2002-01-01

    Full Text Available Chronic fatigue syndrome (CFS is a debilitating illness lacking consistent anatomic lesions and eluding conventional laboratory diagnosis. Demonstration of the utility of the blood for gene expression profiling and biomarker discovery would have implications into the pathophysiology of CFS. The objective of this study was to determine if gene expression profiles of peripheral blood mononuclear cells (PMBCs could distinguish between subjects with CFS and healthy controls. Total RNA from PBMCs of five CFS cases and seventeen controls was labeled and hybridized to 1764 genes on filter arrays. Gene intensity values were analyzed by various classification algorithms and nonparametric statistical methods. The classification algorithms grouped the majority of the CFS cases together, and distinguished them from the healthy controls. Eight genes were differentially expressed in both an age-matched case-control analysis and when comparing all CFS cases to all controls. Several of the diffrentially expressed genes are associated with immunologic functions (e.g., CMRF35 antigen, IL-8, HD protein and implicate immune dysfunction in the pathophysiology of CFS. These results successfully demonstrate the utility of the blood for gene expression profiling to distinguish subjects with CFS from healthy controls and for identifying genes that could serve as CFS biomarkers.

  14. MALDI-MS-Based Profiling of Serum Proteome: Detection of Changes Related to Progression of Cancer and Response to Anticancer Treatment

    Directory of Open Access Journals (Sweden)

    Monika Pietrowska

    2012-01-01

    Full Text Available Mass spectrometry-based analyses of the low-molecular-weight fraction of serum proteome allow identifying proteome profiles (signatures that are potentially useful in detection and classification of cancer. Several published studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. However due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by MALDI/SELDI-ToF spectrometry has been approved for routine diagnostics. Noteworthy, several components of proposed cancer signatures, especially those characteristic for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response. This indicated that among cancer biomarker candidates to be possibly identified by serum proteome profiling were rather those reflecting overall influence of a disease (and the therapy upon the human organism, than products of cancer-specific genes. Current paper focuses on changes in serum proteome that are related to response of patient’s organism to progressing malignancy and toxicity of anticancer treatment. In addition, several methodological issues that affect robustness and interlaboratory reproducibility of MS-based serum proteome profiling are discussed.

  15. Serum protein profiling by solid phase extraction and mass spectrometry: A future diagnostics tool?

    DEFF Research Database (Denmark)

    Callesen, Anne K; Madsen, Jonna S; Vach, Werner

    2009-01-01

    Serum protein profiling by MS is a promising method for early detection of disease. Important characteristics for serum protein profiling are preanalytical factors, analytical reproducibility and high throughput. Problems related to preanalytical factors can be overcome by using standardized...... and rigorous sample collection and sample handling protocols. The sensitivity of the MS analysis relies on the quality of the sample; consequently, the blood sample preparation step is crucial to obtain pure and concentrated samples and enrichment of the proteins and peptides of interest. This review focuses...... on the serum sample preparation step prior to protein profiling by MALDI MS analysis, with particular focus on various SPE methods. The application of SPE techniques with different chromatographic properties such as RP, ion exchange, or affinity binding to isolate specific subsets of molecules (subproteomes...

  16. Serum Immune Profiling for Early Detection of Cervical Disease.

    Science.gov (United States)

    Ewaisha, Radwa; Panicker, Gitika; Maranian, Paul; Unger, Elizabeth R; Anderson, Karen S

    2017-01-01

    The most recent (2012) worldwide estimates from International Agency for Research on Cancer indicate that approximately 528,000 new cases and 270,000 deaths per year are attributed to cervical cancer worldwide. The disease is preventable with HPV vaccination and with early detection and treatment of pre-invasive cervical intraepithelial neoplasia, CIN. Antibodies (Abs) to HPV proteins are under investigation as potential biomarkers for early detection. To detect circulating HPV-specific IgG Abs, we developed programmable protein arrays (NAPPA) that display the proteomes of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). Arrays were probed with sera from women with CIN 0/I (n=78), CIN II/III (n=84), or invasive cervical cancer (ICC, n=83). Abs to any early (E) HPV protein were detected less frequently in women with CIN 0/I (23.7%) than women with CIN II/III (39.0%) and ICC (46.1%, ptypes. HPV protein arrays provide a valuable high-throughput tool for measuring the breadth, specificity, and heterogeneity of the serologic response to HPV in cervical disease.

  17. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    2009-07-01

    Full Text Available Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  18. Effect of alprazolam on rat serum metabolic profiles.

    Science.gov (United States)

    Li, Yan; Lin, Gaotong; Chen, Bingbao; Zhang, Jing; Wang, Lingtian; Li, Zixia; Cao, Yungang; Wen, Congcong; Yang, Xuezhi; Cao, Gaozhong; Wang, Xianqin; Cao, Guoquan

    2017-09-01

    We developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of alprazolam in rats. The GC-MS with HP-5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m/z 50-550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d-glucose, 9,12-octadecadienoic acid, butanoic acid, l-proline, d-mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats. Copyright © 2017 John Wiley & Sons, Ltd.

  19. Prospective evaluation of 64 serum autoantibodies as biomarkers for early detection of colorectal cancer in a true screening setting.

    Science.gov (United States)

    Chen, Hongda; Werner, Simone; Butt, Julia; Zörnig, Inka; Knebel, Phillip; Michel, Angelika; Eichmüller, Stefan B; Jäger, Dirk; Waterboer, Tim; Pawlita, Michael; Brenner, Hermann

    2016-03-29

    Novel blood-based screening tests are strongly desirable for early detection of colorectal cancer (CRC). We aimed to identify and evaluate autoantibodies against tumor-associated antigens as biomarkers for early detection of CRC. 380 clinically identified CRC patients and samples of participants with selected findings from a cohort of screening colonoscopy participants in 2005-2013 (N=6826) were included in this analysis. Sixty-four serum autoantibody markers were measured by multiplex bead-based serological assays. A two-step approach with selection of biomarkers in a training set, and validation of findings in a validation set, the latter exclusively including participants from the screening setting, was applied. Anti-MAGEA4 exhibited the highest sensitivity for detecting early stage CRC and advanced adenoma. Multi-marker combinations substantially increased sensitivity at the price of a moderate loss of specificity. Anti-TP53, anti-IMPDH2, anti-MDM2 and anti-MAGEA4 were consistently included in the best-performing 4-, 5-, and 6-marker combinations. This four-marker panel yielded a sensitivity of 26% (95% CI, 13-45%) for early stage CRC at a specificity of 90% (95% CI, 83-94%) in the validation set. Notably, it also detected 20% (95% CI, 13-29%) of advanced adenomas. Taken together, the identified biomarkers could contribute to the development of a useful multi-marker blood-based test for CRC early detection.

  20. Serum cholinesterase: a potential assistant biomarker for hand, foot, and mouth disease caused by enterovirus 71 infection.

    Science.gov (United States)

    Cheng, Bang-Ning; Jin, Yu-Lian; Chen, Bi-Quan; Zhu, Li-Yan; Xu, Zi-Cheng; Shen, Tao

    2016-03-29

    Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) is a potentially life-threatening infectious disease that commonly occurs in children. Diagnosis of HFMD caused by EV71 largely depends on clinical manifestations and rare serological biomarkers used to identify children suffering from HFMD. Serum cholinesterase (SChE) activity has frequently been reported as a potential biomarker for solid central nervous system tumors, chronic heart failure, and liver cirrhosis. However, its potential value in the diagnosis of neurotropic virus infections, such as HFMD caused by EV71, remains to be determined. In our study, 220 children hospitalized with HFMD caused by EV71, 34 inpatients infected with coxsackievirus A16 (CVA16), and 43 undefined enterovirus-infected HFMD inpatients were recruited at the Anhui Provincial Children's Hospital between January 2011 and December 2012. SChE activity was measured. The non-parametric Mann-Whitney U test showed that SChE activity in children diagnosed with HFMD caused by EV71 was significantly higher than in healthy controls (p  0.05). An important finding was that SChE activity declined in the recovery phase of HFMD caused by EV71 compared to the acute phase (p < 0.001). Elevated SChE activity was observed in patients with severe HFMD caused by EV71. Therefore, SChE might be a potential assistant biomarker for the diagnosis of HFMD caused by EV71 in children.

  1. Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure.

    LENUS (Irish Health Repository)

    Watson, Chris J

    2011-03-01

    Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

  2. Resveratrol metabolite profiling in clinical nutrition research--from diet to uncovering disease risk biomarkers: epidemiological evidence.

    Science.gov (United States)

    Rabassa, Montserrat; Zamora-Ros, Raul; Urpi-Sarda, Mireia; Andres-Lacueva, Cristina

    2015-08-01

    Resveratrol is a bioactive plant compound that has drawn scientific and media attention owing to its protective effects against a wide variety of illnesses, including cardiovascular diseases and cancer. In the last two decades, a plethora of preclinical studies have shown these beneficial effects, and some of them have been supported by clinical trials. However, there are few epidemiological studies assessing these relationships, showing mostly inconsistent results among them. This could be partially due to the difficulty of accurately estimating dietary resveratrol exposure. The development of Phenol-Explorer, a database containing resveratrol food-composition data, will facilitate the estimation of resveratrol intake. Moreover, the discovery and validation of a nutritional biomarker of this exposure, urinary resveratrol metabolite profile, will allow a more accurate assessment of dietary resveratrol exposure. Few epidemiological studies have assessed the potential health effects of resveratrol. Resveratrol was not associated with total mortality, cancer, or cardiovascular events, but it was associated with an improvement of serum glucose and triglyceride levels and a decrease in heart rate. Together, these findings suggest a potential cardioprotective effect of resveratrol in epidemiological studies, although the evidence is still scarce. © 2015 New York Academy of Sciences.

  3. Discovery of serum biomarkers predicting development of a subsequent depressive episode in social anxiety disorder

    NARCIS (Netherlands)

    Gottschalk, M.G.; Cooper, J.D.; Chan, M.K.; Bot, M.; Penninx, B.W.J.H.; Bann, S.

    2015-01-01

    Although social anxiety disorder (SAD) is strongly associated with the subsequent development of a depressive disorder (major depressive disorder or dysthymia), no underlying biological risk factors are known. We aimed to identify biomarkers which predict depressive episodes in SAD patients over a

  4. Early second-trimester serum miRNA profiling predicts gestational diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Chun Zhao

    Full Text Available BACKGROUND: Gestational diabetes mellitus (GDM is one type of diabetes that presents during pregnancy and significantly increases the risk of a number of adverse consequences for the fetus and mother. The microRNAs (miRNA have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. However, no reported study investigates the associations between serum miRNA and GDM. METHODOLOGY/PRINCIPAL FINDINGS: We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to screen miRNAs in serum collected at 16-19 gestational weeks. The expression levels of three miRNAs (miR-132, miR-29a and miR-222 were significantly decreased in GDM women with respect to the controls in similar gestational weeks in our discovery evaluation and internal validation, and two miRNAs (miR-29a and miR-222 were also consistently validated in two-centric external validation sample sets. In addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1 expression level and subsequently the level of Phosphoenolpyruvate Carboxy Kinase2 (PCK2 in HepG2 cell lines. CONCLUSIONS/SIGNIFICANCE: Serum miRNAs are differentially expressed between GDM women and controls and could be candidate biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as serum-based non-invasive biomarkers warrants further evaluation and optimization.

  5. Serum proteomic changes after randomized prolonged erythropoietin treatment and/or endurance training: detection of novel biomarkers.

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    Britt Christensen

    Full Text Available Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA exposure (Darbepoietin-α and/or aerobic training.Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9, Sedentary-ESA (n = 9, Training-placebo (n = 10, or Training-ESA (n = 8. They were treated with placebo/Darbepoietin-α subcutaneously once/week for 10 weeks followed by a 3-week washout period. Training consisted of supervised biking 3/week for 13 weeks at the highest possible intensity. Serum was collected at baseline, week 3 (high dose Darbepoietin-α, week 10 (reduced dose Darbepoietin-α, and after a 3-week washout period.Serum proteins were separated according to charge and molecular mass (2D-gel electrophoresis. The identity of proteins from spots exhibiting altered intensity was determined by mass spectrometry.Six protein spots changed in response to Darbepoietin-α treatment. Comparing all 4 experimental groups, two protein spots (serotransferrin and haptoglobin/haptoglobin related protein showed a significant response to Darbepoietin-α treatment. The haptoglobin/haptoglobin related protein spot showed a significantly lower intensity in all subjects in the training-ESA group during the treatment period and increased during the washout period.An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research.ClinicalTrials.gov NCT01320449.

  6. A semiparametric modeling framework for potential biomarker discovery and the development of metabonomic profiles

    Directory of Open Access Journals (Sweden)

    Dey Dipak K

    2008-01-01

    Full Text Available Abstract Background The discovery of biomarkers is an important step towards the development of criteria for early diagnosis of disease status. Recently electrospray ionization (ESI and matrix assisted laser desorption (MALDI time-of-flight (TOF mass spectrometry have been used to identify biomarkers both in proteomics and metabonomics studies. Data sets generated from such studies are generally very large in size and thus require the use of sophisticated statistical techniques to glean useful information. Most recent attempts to process these types of data model each compound's intensity either discretely by positional (mass to charge ratio clustering or through each compounds' own intensity distribution. Traditionally data processing steps such as noise removal, background elimination and m/z alignment, are generally carried out separately resulting in unsatisfactory propagation of signals in the final model. Results In the present study a novel semi-parametric approach has been developed to distinguish urinary metabolic profiles in a group of traumatic patients from those of a control group consisting of normal individuals. Data sets obtained from the replicates of a single subject were used to develop a functional profile through Dirichlet mixture of beta distribution. This functional profile is flexible enough to accommodate variability of the instrument and the inherent variability of each individual, thus simultaneously addressing different sources of systematic error. To address instrument variability, all data sets were analyzed in replicate, an important issue ignored by most studies in the past. Different model comparisons were performed to select the best model for each subject. The m/z values in the window of the irregular pattern are then further recommended for possible biomarker discovery. Conclusion To the best of our knowledge this is the very first attempt to model the physical process behind the time-of flight mass

  7. Different miRNA expression profiles between human breast cancer turmors and serum

    Directory of Open Access Journals (Sweden)

    Jie eZhu

    2014-05-01

    Full Text Available A bunch of miRNAs have been demonstrated to be aberrantly expressed in cancer tumor tissue and serum. The miRNA signatures identified from the serum samples could serve as potential noninvasive diagnostic markers for breast cancer. The role of the miRNAs in cancerigenesis is unclear. In this study, we generated the expression profiles of miRNAs from the paired breast cancer tumors, normal, tissue, and serum samples from eight patients using small RNA-sequencing. Serum samples from eight healthy individuals were used as normal controls. We identified total 174 significantly differentially expressed miRNAs between tumors and the normal tissues, and 109 miRNAs between serum from patients and serum from healthy individuals. There are only 10 common miRNAs. This suggests that only a small portion of tumor miRNAs are released into serum selectively. Interestingly, the expression change pattern of 28 miRNAs is opposite between breast cancer tumors and serum. Functional analysis shows that the differentially expressed miRNAs and their target genes form a complex interaction network affecting many biological processes and involving in many types of cancer such as prostate cancer, basal cell carcinoma, acute myeloid leukemia, and more.

  8. Gene expression profile of cervical tissue compared to exfoliated cells: Impact on biomarker discovery

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    Vernon Suzanne D

    2005-05-01

    Full Text Available Abstract Background Exfoliated cervical cells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early detection. Results We used whole genome microarrays (25,353 unique genes to compare the transcription profiles from seven samples of normal exfoliated cells and one cervical tissue. We detected 10,158 genes in exfoliated cells, 14,544 in the tissue and 7320 genes in both samples. For both sample types the genes grouped into the same major gene ontology (GO categories in the same order, with exfoliated cells, having on average 20% fewer genes in each category. We also compared microarray results of samples from women with cervical intraepithelial neoplasia grade 3 (CIN3, n = 15 to those from age and race matched women without significant abnormalities (CIN1, CIN0; n = 15. We used three microarray-adapted statistical packages to identify differential gene expression. The six genes identified in common were two to four fold upregulated in CIN3 samples. One of these genes, the ubiquitin-conjugating enzyme E2 variant 1, participates in the degradation of p53 through interaction with the oncogenic HPV E6 protein. Conclusion The findings encourage further exploration of gene expression using exfoliated cells to identify and validate applicable biomarkers. We conclude that the gene expression profile of exfoliated cervical cells partially represents that of tissue and is complex enough to provide potential differentiation between disease and non-disease.

  9. Clinical Proteomics and Cytokine Profiling for Dengue Fever Disease Severity Biomarkers.

    Science.gov (United States)

    Jadhav, Manali; Nayak, Monalisha; Kumar, Swati; Venkatesh, Apoorva; Patel, Sandip K; Kumar, Vipin; Sharma, Sarthak; Samanta, Biaus; Deb, Satarupa; Karak, Avik; Verma, Sumit; Talukdar, Arunansu; Kochar, Sanjay K; Mansukhani, Preeti; Gandhi, Mayuri; Srivastava, Sanjeeva

    2017-11-01

    Dengue fever (DF) is a major global health burden with a pathophysiology that is still incompletely understood. Biomarkers that predict and explain susceptibility to DF and its progression to its more severe hemorrhagic form are much needed. DF is endemic in tropical and subtropical regions of the world, with a rapidly increasing incidence of disease severity. We conducted a clinical biomarker discovery study using both a case-control and longitudinal study design. Plasma proteome alterations in patients with DF (n = 12) and dengue hemorrhagic fever (DHF, n = 24) were analyzed in comparison to healthy controls (HCs, n = 16), using the isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative proteomics methodology (false discovery rate of 1%, ≥2 peptides). Several proteins such as the alpha-2 macroglobulin, angiotensinogen, apolipoprotein B-100, serotransferrin, and ceruloplasmin were upregulated (fold change >1.2) in all DHF cases, and downregulated in DF (fold change <0.83), compared with HCs. Plasma cytokine profiling (8 DF, 8 DHF, and 8 HC) on two consecutive time points, at day 0 (day of admission) and days 5-7, found significant elevation in IL-1RA, IL-7, TNF-α, MCP1-MCAF, and MIP-1β levels, but only in the DHF cases, which is the severe disease, and not in DF, compared with HCs (p < 0.05). These new observations on changes in the plasma proteome and cytokine profiles in patients with dengue infection identify several putative molecular leads for future biomarker development and precision medicine in relation to forecasting DF disease severity.

  10. High-Resolution Taxonomic Profiling of the Subgingival Microbiome for Biomarker Discovery and Periodontitis Diagnosis

    Science.gov (United States)

    Szafranski, Szymon P.; Wos-Oxley, Melissa L.; Vilchez-Vargas, Ramiro; Jáuregui, Ruy; Plumeier, Iris; Klawonn, Frank; Tomasch, Jürgen; Meisinger, Christa; Kühnisch, Jan; Sztajer, Helena; Pieper, Dietmar H.

    2014-01-01

    The oral microbiome plays a key role for caries, periodontitis, and systemic diseases. A method for rapid, high-resolution, robust taxonomic profiling of subgingival bacterial communities for early detection of periodontitis biomarkers would therefore be a useful tool for individualized medicine. Here, we used Illumina sequencing of the V1-V2 and V5-V6 hypervariable regions of the 16S rRNA gene. A sample stratification pipeline was developed in a pilot study of 19 individuals, 9 of whom had been diagnosed with chronic periodontitis. Five hundred twenty-three operational taxonomic units (OTUs) were obtained from the V1-V2 region and 432 from the V5-V6 region. Key periodontal pathogens like Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia could be identified at the species level with both primer sets. Principal coordinate analysis identified two outliers that were consistently independent of the hypervariable region and method of DNA extraction used. The linear discriminant analysis (LDA) effect size algorithm (LEfSe) identified 80 OTU-level biomarkers of periodontitis and 17 of health. Health- and periodontitis-related clusters of OTUs were identified using a connectivity analysis, and the results confirmed previous studies with several thousands of samples. A machine learning algorithm was developed which was trained on all but one sample and then predicted the diagnosis of the left-out sample (jackknife method). Using a combination of the 10 best biomarkers, 15 of 17 samples were correctly diagnosed. Training the algorithm on time-resolved community profiles might provide a highly sensitive tool to detect the onset of periodontitis. PMID:25452281

  11. Heritability and clinical determinants of serum indoxyl sulfate and p-cresyl sulfate, candidate biomarkers of the human microbiome enterotype.

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    Liesbeth Viaene

    Full Text Available BACKGROUND: Indoxyl sulfate and p-cresyl sulfate are unique microbial co-metabolites. Both co-metabolites have been involved in the pathogenesis of accelerated cardiovascular disease and renal disease progression. Available evidence suggests that indoxyl sulfate and p-cresyl sulfate may be considered candidate biomarkers of the human enterotype and may help to explain the link between diet and cardiovascular disease burden. OBJECTIVE AND DESIGN: Information on clinical determinants and heritability of indoxyl sulfate and p-cresyl sulfate serum is non-existing. To clarify this issue, the authors determined serum levels of indoxyl sulfate and p-cresyl sulfate in 773 individuals, recruited in the frame of the Flemish Study on Environment, Genes and Health Outcomes (FLEMENGHO study. RESULTS: Serum levels of indoxyl sulfate and p-cresyl sulfate amounted to 3.1 (2.4-4.3 and 13.0 (7.4-21.5 μM, respectively. Regression analysis identified renal function, age and sex as independent determinants of both co-metabolites. Both serum indoxyl sulfate (h2 = 0.17 and p-cresyl sulfate (h2 = 0.18 concentrations showed moderate but significant heritability after adjustment for covariables, with significant genetic and environmental correlations for both co-metabolites. LIMITATIONS: Family studies cannot provide conclusive evidence for a genetic contribution, as confounding by shared environmental effects can never be excluded. CONCLUSIONS: The heritability of indoxyl sulfate and p-cresyl sulfate is moderate. Besides genetic host factors and environmental factors, also renal function, sex and age influence the serum levels of these co-metabolites.

  12. Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes.

    Directory of Open Access Journals (Sweden)

    Natalia V Voge

    2016-02-01

    Full Text Available Epidemic dengue fever (DF and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS are overwhelming public health capacity for diagnosis and clinical care of dengue patients throughout the tropical and subtropical world. The ability to predict severe dengue disease outcomes (DHF/DSS using acute phase clinical specimens would be of enormous value to physicians and health care workers for appropriate triaging of patients for clinical management. Advances in the field of metabolomics and analytic software provide new opportunities to identify host small molecule biomarkers (SMBs in acute phase clinical specimens that differentiate dengue disease outcomes.Exploratory metabolomic studies were conducted to characterize the serum metabolome of patients who experienced different dengue disease outcomes. Serum samples from dengue patients from Nicaragua and Mexico were retrospectively obtained, and hydrophilic interaction liquid chromatography (HILIC-mass spectrometry (MS identified small molecule metabolites that were associated with and statistically differentiated DHF/DSS, DF, and non-dengue (ND diagnosis groups. In the Nicaraguan samples, 191 metabolites differentiated DF from ND outcomes and 83 differentiated DHF/DSS and DF outcomes. In the Mexican samples, 306 metabolites differentiated DF from ND and 37 differentiated DHF/DSS and DF outcomes. The structural identities of 13 metabolites were confirmed using tandem mass spectrometry (MS/MS. Metabolomic analysis of serum samples from patients diagnosed as DF who progressed to DHF/DSS identified 65 metabolites that predicted dengue disease outcomes. Differential perturbation of the serum metabolome was demonstrated following infection with different DENV serotypes and following primary and secondary DENV infections.These results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum specimens that are associated with distinct DENV infections and

  13. Serum galectin-1 in patients with multiple myeloma: associations with survival, angiogenesis, and biomarkers of macrophage activation

    Directory of Open Access Journals (Sweden)

    Andersen MN

    2017-04-01

    Full Text Available Morten Nørgaard Andersen,1–3,* Maja Ludvigsen,1,3,* Niels Abildgaard,4 Irma Petruskevicius,3 Rikke Hjortebjerg,5 Mette Bjerre,5 Bent Honoré,1 Holger J Møller,2 Niels F Andersen31Department of Biomedicine, Faculty of Health, Aarhus University, 2Department of Clinical Biochemistry, 3Department of Hematology, Aarhus University Hospital, Aarhus, 4Department of Hematology, Odense University Hospital, Odense, 5Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark*These authors contributed equally to this workAbstract: Galectin-1 (Gal-1 is known to regulate cell signaling within the immune system and may be a target for new anticancer immune therapy. In patients with chronic lymphocytic leukemia (CLL and classical Hodgkin lymphoma (cHL, high levels of Gal-1 within the tumor microenvironment were associated with worse disease state or poor outcome. Gal-1 can be secreted from cells by an unknown mechanism, and levels in blood samples were associated with high tumor burden and worse disease state in cHL and CLL patients. However, serum levels of Gal-1 have never been investigated in patients with multiple myeloma (MM. We measured serum Gal-1 levels in samples from patients with treatment demanding MM at the time of diagnosis (n=102 and after treatment (n=24 and examined associations of serum Gal-1 with clinicopathological information obtained from patient medical records, as well as data on bone marrow angiogenesis and the macrophage activation biomarkers soluble CD163 (sCD163 and soluble mannose receptor. Serum Gal-1 levels were not elevated in patients with MM at diagnosis compared with healthy donors (median values 8.48 vs 11.93 ng/mL, P=0.05, which is in contrast to results in cHL and CLL. Furthermore, Gal-1 levels did not show association with bone marrow angiogenesis, clinicopathological parameters, overall survival, or response to treatment. There was a statically significant

  14. Serum CA125 and NSE: biomarkers of disease severity in patients with silicosis.

    Science.gov (United States)

    Fang, Shen-Cun; Zhang, Hai-Tao; Wang, Cai-Ying; Zhang, Ying-Ming

    2014-06-10

    We investigated the clinical significance of tumor markers in patients with silicosis. Eighty silicosis patients without malignancy and 50 healthy volunteers were compared for serum tumor marker concentrations. Pulmonary function and several routine laboratory tests were performed. Correlation between serum tumor marker concentrations and severity markers for silicosis was analyzed. Tumor marker concentrations were detected in both blood and BALF samples in silicosis patients. The pre- and post-lavage differences in the serum tumor marker concentrations were also investigated. Immunohistochemical staining for tumor markers was performed in a lung biopsy specimen from a silicosis patient. Both serum NSE and CA125 concentrations were significantly higher in cases compared with controls. Significant positive correlations were found between values of NSE and CA125 and LDH concentration. Significant negative correlations were also observed between values of NSE and CA125 and spirometric parameters. Patients with silicosis had higher concentrations of NSE in BALF than that in serum. 11 of 14 patients experienced a decrease in NSE concentrations following whole lung lavage. Immunohistochemical studies showed positive NSE staining in lung biopsy specimen. Serum NSE and CA125 concentrations would provide valuable clinical information to assess disease severity in silicosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. μPAD Fluorescence Scattering Immunoagglutination Assay for Cancer Biomarkers from Blood and Serum.

    Science.gov (United States)

    Baynes, Cayla; Yoon, Jeong-Yeol

    2017-09-01

    A microfluidic paper analytical device (μPAD) was created for the sensitive quantification of cancer antigens, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9), from human whole blood and serum, toward diagnosis and prognosis of colorectal cancer. Anti-CEA and anti-CA 19-9 antibodies were covalently linked to submicron, fluorescent polystyrene particles, loaded, and then dried in the center of the μPAD channel. CEA- or CA 19-9-spiked blood or serum samples were loaded to the inlet of μPAD, and subsequent immunoagglutination changed the fluorescent scatter signals upon ultraviolet (UV) excitation. The total assay time was about 1 min. Detection limits were 1 pg/mL for CEA and 0.1 U/mL for CA 19-9 from both 10% diluted blood and undiluted serum. The use of UV excitation and subsequent fluorescence scattering enabled much higher double-normalized intensities (up to 1.28-3.51, compared with 1.067 with the elastic Mie scatter detection), successful detection in the presence of blood or serum, and distinct multiplex assays with minimum cross-reaction of antibodies. The results with undiluted serum showed the larger dynamic range and smaller standard errors, which can be attributed to the presence of serum proteins, functioning as a stabilizer or a passivating protein for the particles within paper fibers.

  16. Açai (Euterpe oleracea Mart.) pulp dietary intake improves cellular antioxidant enzymes and biomarkers of serum in healthy women.

    Science.gov (United States)

    Barbosa, Priscila Oliveira; Pala, Daniela; Silva, Carla Teixeira; de Souza, Melina Oliveira; do Amaral, Joana Ferreira; Vieira, Renata Adrielle Lima; Folly, Gilce Andrezza de Freitas; Volp, Ana Carolina Pinheiro; de Freitas, Renata Nascimento

    2016-06-01

    The aim of the present study was to evaluate the effect of açai pulp (Euterpe oleracea Martius) intake on the prevention of oxidative damage by measuring the activity of antioxidant enzymes and biomarkers of protein oxidation in women. A nutritional intervention study was conducted with thirty-five healthy women who were asked to consume 200 g/d of açai pulp for 4 wk. Blood samples were collected, and blood pressure and anthropometric parameters were measured before and after the experimental period. Antioxidant enzymes, superoxide dismutase, catalase, glutathione, production of reactive oxygen species, and total antioxidant capacity were evaluated in polymorphonuclear cells. Serum concentration of protein carbonyl and sulfhydryl groups were also determined. The açai intake increased catalase activity, total antioxidant capacity, and reduced the production of reactive oxygen species. Furthermore, it reduced serum concentration of protein carbonyl and increased total serum sulfhydryl groups. These results show the antioxidant benefit of dietary açai for the healthy women included in the present study, and may increase understanding of the beneficial health properties of this fruit. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Elevated Serum Levels of Cysteine and Tyrosine: Early Biomarkers in Asymptomatic Adults at Increased Risk of Developing Metabolic Syndrome

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    Nina Mohorko

    2015-01-01

    Full Text Available As there is effective intervention for delaying or preventing metabolic diseases, which are often present for years before becoming clinically apparent, novel biomarkers that would mark metabolic complications before the onset of metabolic disease should be identified. We investigated the role of fasting serum amino acids and their associations with inflammatory markers, adipokines, and metabolic syndrome (MetS components in subjects prior to the onset of insulin resistance (IR. Anthropometric measurements, food records, adipokines, biochemical markers, and serum levels of amino acids were determined in 96 asymptomatic subjects aged 25–49 years divided into three groups according to the number of MetS components present. Cysteine and tyrosine were significantly higher already in group with one component of MetS present compared to subjects without MetS components. Serum amino acid levels correlated with markers of inflammation and adipokines. Alanine and glycine explained 10% of insulin resistance variability. The role of tyrosine and cysteine, that were higher already with 1 component of MetS present, should be further investigated as they might point to future insulin disturbances.

  18. Serum lipid profile of Nigerian diabetics with end stage renal disease

    African Journals Online (AJOL)

    Summary. Background: End stage renal disease (ESRD) and diabetes mellitus may have lipid abnormalities that act synergistically to place diabetics with ESRD at an augmented risk for cardiovascular morbidity and mortality. We studied serum lipid profile and risk ratio in Nigerian diabetics with ESRD as there is no data in ...

  19. Effect of Oral Vitamin E on Serum Lipid Profile of Apparently Healthy ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of oral vitamin E on serum lipid profile of Apparently Healthy. Nigerians in Benin City. Methods: Fifty eight apparently healthy non-smoking males aged 30 - 59 years were randomly selected from Benin metropolis and were divided in three groups. The effect of oral vitamin E (a potent.

  20. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    Science.gov (United States)

    HUMAN OZONE (O3) EXPOSURE ALTERS SERUM PROFILE OF LIPID METABOLITES Miller, D B.1; Kodavanti, U P.2 Karoly, E D.3; Cascio W.E2, Ghio, A J. 21. UNC-Chapel Hill, Chapel Hill, N.C., United States. 2. NHEERL, U.S. EPA, RTP, N.C., United States. 3. METABOLON INC., Durham, N.C., United...

  1. Effects of folic acid intake on serum lipid profiles of apparently ...

    African Journals Online (AJOL)

    Effects of folic acid intake on serum lipid profiles of apparently healthy young adult male Nigerians. ... If you would like more information about how to print, save, and work with PDFs, Highwire Press provides a helpful Frequently Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your ...

  2. Effect of soy protein on serum lipid profile and some lipid ...

    African Journals Online (AJOL)

    The effect of soy protein on serum lipid profile and some lipid metabolizing enzymes in rats fed with cholesterol diets was examined in this study. Rats were subjected to feeding trial over a period of six weeks on formulated diets containing: 20% soy protein with 0% cholesterol (group A), 20% soy protein with 5% cholesterol ...

  3. Serum lipid profile of Nigerian diabetics with end stage renal disease

    African Journals Online (AJOL)

    Background: End stage renal disease (ESRD) and diabetes mellitus may have lipid abnormalities that act synergistically to place diabetics with ESRD at an augmented risk for cardiovascular morbidity and mortality. We studied serum lipid profile and risk ratio in Nigerian diabetics with ESRD as there is no data in this regard ...

  4. Effect of Oral Vitamin E on Serum Lipid Profile of Apparently Healthy ...

    African Journals Online (AJOL)

    Purpose: To investigate the effect of oral vitamin E on serum lipid profile of Apparently Healthy Nigerians in Benin City Methods: Fifty eight apparently healthy non-smoking males aged 30 - 59 years were randomly selected from Benin metropolis and were divided in three groups. The effect of oral vitamin E (a potent ...

  5. Maternal Serum B-Cell Activating Factor Levels: Candidate Early Biomarker for Hypertensive Disorders of Pregnancy.

    Science.gov (United States)

    Stohl, Hindi E; Lee, Richard H; Manetta, Joseph; Kikly, Kristine; Korst, Lisa M; Stohl, William

    2017-11-01

    Hypertensive disorders of pregnancy are a leading cause of maternal and perinatal morbidity and mortality. Early suppression of B-cell lymphopoiesis is necessary for a normal pregnancy. Dysregulation of factors critical to B-cell survival may result in pregnancy complications, including hypertension. In this prospective observational study at a single medical center, serum levels of BAFF (B-cell activating factor) were measured in pregnant participants at each trimester, at delivery, and postpartum and in nonpregnant controls at a single time point. Comparisons were made between nonpregnant and pregnant subjects and between time periods of pregnancy. First-trimester serum BAFF levels were further tested for association with hypertensive disorders of pregnancy. The study included 149 healthy pregnant women, 25 pregnant women with chronic hypertension, and 48 nonpregnant controls. Median first-trimester serum BAFF level (ng/mL) for healthy women (0.90) was lower than median serum BAFF levels for women with chronic hypertension (0.96; P=0.013) and controls (1.00; P=0.002). Serum BAFF levels steadily declined throughout pregnancy, with the median second-trimester level lower than the corresponding first-trimester level (0.77; P=0.003) and the median third-trimester level lower than the corresponding second-trimester level (0.72; P=0.025). The median first-trimester serum BAFF level was elevated in women who subsequently developed hypertension compared with women who remained normotensive (1.02 versus 0.85; P=0.012), with the area under the receiver operating characteristic curve being 0.709. First-trimester serum BAFF level may be an early and clinically useful predictor of hypertensive disorders of pregnancy. © 2017 American Heart Association, Inc.

  6. Development and validation of a skin fibroblast biomarker profile for schizophrenic patients

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    Marianthi Logotheti

    2016-12-01

    Full Text Available Gene expression profiles of non-neural tissues through microarray technology could be used in schizophrenia studies, adding more information to the results from similar studies on postmortem brain tissue. The ultimate goal of such studies is to develop accessible biomarkers. Supervised machine learning methodologies were used, in order to examine if the gene expression from skin fibroblast cells could be exploited for the classification of schizophrenic subjects. A dataset of skin fibroblasts gene expression of schizophrenia patients was obtained from Gene Expression Omnibus database. After applying statistical criteria, we concluded to genes that present a differential expression between the schizophrenic patients and the healthy controls. Based on those genes, functional profiling was performed with the BioInfoMiner web tool. After the statistical analysis, 63 genes were identified as differentially expressed. The functional profiling revealed interesting terms and pathways, such as mitogen activated protein kinase and cyclic adenosine monophosphate signaling pathways, as well as immune-related mechanisms. A subset of 16 differentially expressed genes from fibroblast gene expression profiling that occurred after Support Vector Machines Recursive Feature Elimination could efficiently separate schizophrenic from healthy controls subjects. These findings suggest that through the analysis of fibroblast based gene expression signature and with the application of machine learning methodologies we might conclude to a diagnostic classification model in schizophrenia.

  7. Serum biomarkers for personalization of nanotherapeutics-based therapy in different tumor and organ microenvironments.

    Science.gov (United States)

    Yokoi, Kenji; Tanei, Tomonori; Godin, Biana; van de Ven, Anne L; Hanibuchi, Masaki; Matsunoki, Aika; Alexander, Jenolyn; Ferrari, Mauro

    2014-04-01

    Enhanced permeation and retention (EPR) effect, the mechanism by which nanotherapeutics accumulate in tumors, varies in patients based on differences in the tumor and organ microenvironment. Surrogate biomarkers for the EPR effect will aid in selecting patients who will accumulate higher amounts of nanotherapeutics and show better therapeutic efficacy. Our data suggest that the differences in the vascular permeability and pegylated liposomal doxorubicin (PLD) accumulation are tumor type as well as organ-specific and significantly correlated with the relative ratio of MMP-9 to TIMP-1 in the circulation, supporting development of these molecules as biomarkers for the personalization of nanoparticle-based therapy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. EFFECT OF FEEDING CANOLA AND SOYBEAN OILS ON SERUM LIPID PROFILE IN COMMERCIAL LAYERS

    Directory of Open Access Journals (Sweden)

    Shakoor. H. I., M. L. Khan, Z. Nasir, N. Mukhtar and M. S. Rehman

    2002-04-01

    Full Text Available The purpose of this study was to assess the effect of canola oil and soybean oil on production performance and serum lipid profile in layers. In this study 15 experimental units (8 layers per experimental unit were randomly allotted to 5 different dietary treatments viz control (A. containing 2.5 % canola oil (B, 5% canola oil (C, 2.5% soybean oil (D and 5% soybean oil (E for a period of 9 weeks. Effects of five treatments on production parameters including egg production, egg quality, weight gain and serum lipid profile, serum cholesterol, triglycerides, low-density lipoprotein and high-density lipoprotein were monitored. Serum lipid profile was determined 0.31 and 63 days from start of experiment. Significantly (P<0.05 less serum cholesterol was found in treatment C (295.1 mg/dl as compared with treatment A (321 mg/dl. Low density lipoprotein cholesterol (LDL was significantly (P<0.01 , less in treatment C ( 131.7 mg/dl as compared with treatment A. ( 161 mg/dl and high density lipoprotein cholesterol (HDL was significantly (P<0.01 high in treatment C (31.76 mg/dl as compared with treatment A (25.42 mg/dl and triglyceride (TG was found significantly (P<0.01 less in treatment E ( 907.3 mg/dl as compared with treatment A (960 mg/dl. The results suggested that as the percentage of oils increased in the diet, serum lipid profile showed a positive trend.

  9. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nomura, Fumio, E-mail: fnomura@faculty.chiba-u.jp [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide [Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University and Divisions of Laboratory Medicine, Clinical Genetics and Proteomics, Chiba University Hospital, Chiba (Japan); Tomonaga, Takeshi [Laboratory of Proteome Research, National Institute of Biomedical Innovation, Ibaraki (Japan); Yoshitomi, Hideyuki [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Imazeki, Fumio [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan); Takizawa, Hirotaka [Kashiwado Clinic in Port-Square of the Kashiwado Memorial Foundation, Chiba (Japan); Mogushi, Kaoru [Information Center for Medical Sciences, Tokyo Dental and Medical University, Tokyo (Japan); Miyazaki, Masaru [Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba (Japan); Yokosuka, Osamu [Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba (Japan)

    2012-05-18

    stage I solitary tumor <2 cm in diameter, whereas the sensitivities of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II) were 17.8% and 21.4%, respectively. The results of ROC analyses indicated the better performance of anti-Ku86 for early detection of HCC. Serum anti-Ku86 levels decreased after surgical resection of the tumors in the 12 HCC cases tested, Elevation of anti-Ku86 in solid tumors other than liver was minimal. Serum anti-Ku86 is a potential biomarker for early detection of HCV-related HCC. Further studies in a larger number of HCC patients with various etiologies are needed to further evaluate the diagnostic and pathophysiological roles of elevation of serum anti-Ku86 in early HCC.

  10. Novel Autoantibody Serum and Cerebrospinal Fluid Biomarkers in Veterans with Gulf War Illness

    Science.gov (United States)

    2017-10-01

    that is consistent with their complaints. Such consequence should give them a peace of mind . Our biomarker should lead studies to develop treatment...significant impact on expenditures o None  Significant changes in use or care of human subjects, vertebrate animals , biohazards, and/or select...agents: o Significant changes in use or care of human subjects: None o Significant changes in use or care of vertebrate animals : None o Significant

  11. Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia.

    Science.gov (United States)

    Nganvongpanit, Korakot; Itthiarbha, Akanit; Ong-Chai, Siriwan; Kongtawelert, Prachya

    2008-09-01

    Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 +/- 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 +/- 208.97 ng/ml) (p dogs.

  12. Multigene methylation in serum of sporadic Chinese female breast cancer patients as a prognostic biomarker.

    Science.gov (United States)

    Jing, Feng; Jun, Lu; Yong, Zhang; Wang, Yuping; Fei, Xie; Zhang, Jicai; Hu, Lihua

    2008-01-01

    DNA methylation is a common molecular alteration in human neoplasia and can be detected easily in the bloodstream of patients. Here, we investigated whether DNA methylation in sera is of prognostic significance in breast cancer patients. Methylation status of BRCA1, p16 and 14-3-3sigma was examined by methylation-specific PCR assay in the sera of sporadic breast cancer patients and healthy serum controls. The panel gene methylation frequencies were 29% of sporadic breast cancers for p16, 32% for BRCA1 and 82% for 14-3-3sigma; all were significantly associated with grades and estrogen receptor status. Only p16 methylation was associated with histological type. p16 and BRCA1 methylation were associated with progesterone receptor status, while 14-3-3sigma was significantly associated with lymph node metastases. Seventy percent of patients with p16 methylation showed elevated serum CEA levels; of the breast cancer patients with BRCA1 methylation, 75.8% showed elevated serum CEA levels and 69.7% showed elevated serum CA15.3 levels. When analyzing all investigated patients, multivariate analysis showed methylated BRCA1 and/or p16 serum DNA to be independently associated with poor outcome, with a relative risk of death of 6.0. Epigenetic markers in sera, especially BRCA1/p16, may be more promising targets for the diagnosis of sporadic breast cancer than previous prognostic markers. Copyright 2008 S. Karger AG, Basel.

  13. Serum biomarker levels for musculoskeletal disease in two- and three-year-old racing Thoroughbred horses: A prospective study of 130 horses.

    Science.gov (United States)

    Frisbie, D D; Mc Ilwraith, C W; Arthur, R M; Blea, J; Baker, V A; Billinghurst, R C

    2010-10-01

    Biomarkers have shown some in vivo promise for the detection of musculoskeletal injuries, but further study to assess biomarker levels in clinical orthopaedic disease is required. To assess 7 serum biomarkers for the detection of musculoskeletal injuries. Two- and 3-year-old racehorses were entered into the study (n = 238). Exit criteria were lack of training for >30 days, or completion of 10 study months. Data from horses with solitary musculoskeletal injuries and completion of >2 months were analysed. Musculoskeletal injury was considered intra-articular fragmentation (IAF), tendon or ligamentous injury (TL), stress fractures (SF) and dorsal metacarpal disease (DMD). Monthly lameness examination and serum collection were performed. Serum was analysed for glycosaminoglycan (GAG), type I and II collagen degradation (C1, 2C), type II collagen synthesis (CPII), type II collagen degradation (Col CEQ), aggrecan synthesis (CS846), osteocalcin (OC) as a marker of bone formation and (C-terminal telopeptide of type I collagen) CTX as a marker of bone degradation. Of the 238 horses 59 injured and 71 uninjured control horses met the analysis criteria. Based on injury no significant differences in the proportions were observed for age, gender or lesion type, although a higher proportion of injuries occurred at the beginning of the study. Of injured horses, 16 (27%) sustained an IAF, 17 (29%) a TL injury, 7 (12%) SF and 19 (32%) were diagnosed with DMD. There were significant changes seen in biomarkers based on the injury incurred when longitudinal samples were assessed. Furthermore, based on the serum biomarkers collected prior to injury, horses could be correctly classified as injured or uninjured 73.8% of the time. A unique biomarker pattern occurred before each injury and this was beneficial in classifying horses as injured or uninjured. Biomarkers have the potential to be used as a screening aid prior to musculoskeletal injury. © 2010 EVJ Ltd.

  14. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    Directory of Open Access Journals (Sweden)

    Fabiana Azevedo Voorwald

    Full Text Available Cystic endometrial hyperplasia (CEH, mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes. Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%, with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.

  15. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions

    Science.gov (United States)

    Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer

    2015-01-01

    Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. PMID:26222498

  16. Differential Proteomics Identification of HSP90 as Potential Serum Biomarker in Hepatocellular Carcinoma by Two-dimensional Electrophoresis and Mass Spectrometry

    OpenAIRE

    Sun, Yiyi; Zang, Zhihe; Xu, Xiaohong; Zhang, Zhonglin; Zhong, Ling; Zan, Wang; Zhao, Yan; Sun, Lin

    2010-01-01

    The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patie...

  17. Repeatability of and relationship between potential COPD biomarkers in bronchoalveolar lavage, bronchial biopsies, serum, and induced sputum.

    Directory of Open Access Journals (Sweden)

    Stefan Röpcke

    Full Text Available Chronic Obstructive Pulmonary Disease (COPD is a chronic inflammatory disease, primarily affecting the airways. Stable biomarkers characterizing the inflammatory phenotype of the disease, relevant for disease activity and suited to predict disease progression are needed to monitor the efficacy and safety of drug interventions. We therefore analyzed a large panel of markers in bronchoalveolar lavage, bronchial biopsies, serum and induced sputum of 23 healthy smokers and 24 smoking COPD patients (GOLD II matched for age and gender. Sample collection was performed twice within a period of 6 weeks. Assays for over 100 different markers were validated for the respective matrices prior to analysis. In our study, we found 51 markers with a sufficient repeatability (intraclass correlation coefficient >0.6, most of these in serum. Differences between groups were observed for markers from all compartments, which extends (von-Willebrand-factor and confirms (e.g. C-reactive-protein, interleukin-6 previous findings. No correlations between lung and serum markers were observed, including A1AT. Airway inflammation defined by sputum neutrophils showed only a moderate repeatability. This could be improved, when a combination of neutrophils and four sputum fluid phase markers was used to define the inflammatory phenotype.In summary, our study provides comprehensive information on the repeatability and interrelationship of pulmonary and systemic COPD-related markers. These results are relevant for ongoing large clinical trials and future COPD research. While serum markers can discriminate between smokers with and without COPD, they do not seem to sufficiently reflect the disease-associated inflammatory processes within the airways.

  18. Serum microRNA profiles in patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, or drug-induced liver injury.

    Science.gov (United States)

    Yamaura, Yu; Tatsumi, Naoyuki; Takagi, Shingo; Tokumitsu, Shinsaku; Fukami, Tatsuki; Tajiri, Kazuto; Minemura, Masami; Yokoi, Tsuyoshi; Nakajima, Miki

    2017-12-01

    Some blood biomarkers or histological examination by liver biopsy are used for the diagnosis of liver diseases in clinics. However, conventional blood biomarkers show poor specificity and sensitivity, and liver biopsy is highly invasiveness. Therefore, to overcome such disadvantages, specific/sensitive and noninvasive options are desirable. In recent years, circulating microRNAs (miRNAs) have been acknowledged for their potential as disease markers. Actually, several miRNAs have been reported to be biomarker candidates of liver diseases. However, these earlier studies were performed for one disease. Therefore, the specificity as biomarkers was not guaranteed, because they didn't study for the other types of liver injury. In this study, we examined if circulating miRNA could distinguish different types of liver diseases. Serum miRNA profiles in 28 patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis or drug-induced liver injury as well as 4 control subjects were determined by TaqMan MicroRNA Array analysis. Principal component analysis (PCA) of selected miRNAs was performed. We identified 37 miRNAs whose levels were significantly different between any of the groups. Although individual miRNAs could not distinguish different types of liver diseases, probably because of similar liver pathology, their profiling by PCA could classify different liver disease groups. The profiling of the selected miRNAs can be useful to distinguish different types of liver diseases. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  19. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    Science.gov (United States)

    Gao, Rong; Cheng, Jianhua; Fan, Chunlei; Shi, Xiaofeng; Cao, Yuan; Sun, Bo; Ding, Huiguo; Hu, Chengjin; Dong, Fangting; Yan, Xianzhong

    2015-12-01

    Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

  20. Serum biochemical parameters and cytokine profiles associated with natural African trypanosome infections in cattle.

    Science.gov (United States)

    Bakari, Soale Majeed; Ofori, Jennifer Afua; Kusi, Kwadwo Asamoah; Aning, George Kwame; Awandare, Gordon Akanzuwine; Carrington, Mark; Gwira, Theresa Manful

    2017-06-27

    Animal African trypanosomiasis (AAT) greatly affects livestock production in sub-Saharan Africa. In Ghana prevalence of AAT is estimated to range between 5 and 50%. Studies have reported serum biochemical aberrations and variability in cytokine profiles in animals during infection. However, information regarding the biochemical parameters and cytokine profiles associated with natural infections are limited. This study was therefore aimed at investigating changes in the levels of serum biochemical parameters and inflammatory cytokines during a natural infection. Nested internal transcribed spacer (ITS)-based PCR and sequencing were used to characterise trypanosome infection in cattle at two areas in Ghana (Adidome and Accra) of different endemicities. The cattle were sampled at four to five-week intervals over a period of six months. Levels of serum biochemical parameters, including creatinine, cholesterol, alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bilirubin and total protein and cytokines (interleukin 10, interleukin 4, interleukin 12, interferon gamma and tumor necrosis factor alpha) were measured in serum samples and then compared between infected cattle and uninfected controls. The predominant trypanosome species detected in Accra (non-endemic) and Adidome (endemic) were Trypanosoma theileri and Trypanosoma vivax, respectively. Serum biochemical parameters were similar between infected and uninfected cattle in Accra. Infected cattle at Adidome however, had significantly higher levels of ALP, creatinine, total protein and total bilirubin (P biochemical alterations whereas cattle in a non-endemic area with predominantly chronic T. theileri infections demonstrate high anti-inflammatory response and no biochemical alterations.

  1. Serum Levels of Stress Hormones and Oxidative Stress Biomarkers Differ according to Sasang Constitutional Type

    Directory of Open Access Journals (Sweden)

    Hyeong Geug Kim

    2015-01-01

    Full Text Available Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS, and malondialdehyde (MDA were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p<0.1 in both sexes and Soyangin (p<0.05 in males and p<0.1 in females. The adrenaline levels were also significantly lower in Taeumin than in Soumin (p<0.05 in males and p<0.1 in females and Soyangin (p<0.1 in males. Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p<0.05 in males, whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p<0.05 in males and p<0.1 in females. Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types.

  2. Serum interleukin-6 as a prognostic biomarker in patients with metastatic melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Johansen, Julia S

    2012-01-01

    Interleukin-6 (IL-6) is an immunomodulatory cytokine produced by both normal cells and tumor cells, including melanoma cells. The specific biological function of IL-6 in melanoma is unknown. The present study examined whether the serum concentration of IL-6 can predict prognosis in patients...

  3. Serum alkylresorcinols as biomarkers of dietary gluten exposure in coeliac disease.

    Science.gov (United States)

    Choung, R S; Murray, J A; Marietta, E V; Van Dyke, C T; Ross, A B

    2017-03-01

    Therapy for coeliac disease (CD) mainly relies on following a gluten-free diet (GFD); however, a serum marker for gluten intake has yet to be established. To evaluate the utility of alkylresorcinol concentrations for detecting gluten intake in studies of human and mouse. Alkylresorcinol concentrations were compared among treated patients with coeliac disease (n = 34), untreated coeliac disease patients (n = 36) and controls (n = 33). Furthermore, seven additional coeliac disease patients whose serum samples were available at diagnosis and after GFD were evaluated. In mice studies, alkylresorcinol concentrations were compared in the serum of five mice fed a regular chow and 10 mice fed lifelong with a gluten-free chow. In addition, the effect of adding gluten on changes of alkylresorcinol concentrations was also evaluated. Total alkylresorcinol concentrations were significantly lower in treated with coeliac disease [median (IQR), 3 (2-8) nmol/L], compared to untreated patients [median (IQR), 32 (11-74) nmol/L; P gluten-free chow was 1.8 (1.6-2.3) nmol/L, which was further significantly increased to 16 (11-22) nmol/L after 8 days of feeding with the gluten-free chow that had gluten added to it. (P = 0.008). Serum alkylresorcinol concentrations could be a useful marker for dietary gluten in coeliac disease. © 2017 John Wiley & Sons Ltd.

  4. Serum Cytokines as Biomarkers in Islet Cell Transplantation for Type 1 Diabetes

    NARCIS (Netherlands)

    van der Torren, Cornelis R; Verrijn Stuart, Annemarie A|info:eu-repo/dai/nl/304817589; Lee, DaHae; Meerding, Jenny; van de Velde, Ursule; Pipeleers, Daniel; Gillard, Pieter; Keymeulen, Bart; de Jager, Wilco|info:eu-repo/dai/nl/304816906; Roep, Bart O

    2016-01-01

    BACKGROUND: Islet cell transplantation holds a potential cure for type 1 diabetes, but many islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of islet

  5. Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2016-08-01

    Full Text Available Background/Aims: Abnormal potassium profiles are common in peritoneal dialysis (PD patients. We studied the factors associated with serum potassium profiles in incident PD patients. Methods: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. Results: There were 168 men and 151 women (mean age, 50.8 years. Blood urea nitrogen (BUN, creatinine (Cr, and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001 and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029 levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. Conclusion: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.

  6. Genome-wide Association Study Identifies Genes for Biomarkers of Cardiovascular Disease: Serum Urate and Dyslipidemia

    Science.gov (United States)

    Wallace, Chris; Newhouse, Stephen J.; Braund, Peter; Zhang, Feng; Tobin, Martin; Falchi, Mario; Ahmadi, Kourosh; Dobson, Richard J.; Marçano, Ana Carolina B.; Hajat, Cother; Burton, Paul; Deloukas, Panagiotis; Brown, Morris; Connell, John M.; Dominiczak, Anna; Lathrop, G. Mark; Webster, John; Farrall, Martin; Spector, Tim; Samani, Nilesh J.; Caulfield, Mark J.; Munroe, Patricia B.

    2008-01-01

    Summary Many common diseases are accompanied by disturbances in biochemical traits. Identifying the genetic determinants could provide novel insights into disease mechanisms and reveal avenues for developing new therapies. Here, we report a genome-wide association analysis for commonly measured serum and urine biochemical traits. As part of the WTCCC, 500,000 SNPs genome wide were genotyped in 1955 hypertensive individuals characterized for 25 serum and urine biochemical traits. For each trait, we assessed association with individual SNPs, adjusting for age, sex, and BMI. Lipid measurements were further examined in a meta-analysis of genome-wide data from a type 2 diabetes scan. The most promising associations were examined in two epidemiological cohorts. We discovered association between serum urate and SLC2A9, a glucose transporter (p = 2 × 10−15) and confirmed this in two independent cohorts, GRAPHIC study (p = 9 × 10−15) and TwinsUK (p = 8 × 10−19). The odds ratio for hyperuricaemia (defined as urate >0.4 mMol/l) is 1.89 (95% CI = 1.36–2.61) per copy of common allele. We also replicated many genes previously associated with serum lipids and found previously recognized association between LDL levels and SNPs close to genes encoding PSRC1 and CELSR2 (p = 1 × 10−7). The common allele was associated with a 6% increase in nonfasting serum LDL. This region showed increased association in the meta-analysis (p = 4 × 10−14). This finding provides a potential biological mechanism for the recent association of this same allele of the same SNP with increased risk of coronary disease. PMID:18179892

  7. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.

    Science.gov (United States)

    Specht, Ina Olmer; Toft, Gunnar; Hougaard, Karin S; Lindh, Christian H; Lenters, Virissa; Jönsson, Bo A G; Heederik, Dick; Giwercman, Aleksander; Bonde, Jens Peter E

    2014-05-01

    Phthalates which are widely used, are ubiquitous in the environment and in some human tissues. It is generally accepted that phthalates exert their toxic action by inhibiting Leydig cell synthesis of testosterone, but in vitro studies have also shown anti-androgenic effects at the receptor level. Some cross-sectional studies have shown inverse associations between urinary levels of phthalates and reproductive hormones, but results are conflicting and the evidence base is limited. The aim of this study was to investigate if levels of di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) metabolites in serum are associated with serum concentrations of male reproductive hormones and semen quality. A secondary aim was to investigate metabolic pathways of DEHP and DiNP on semen quality and reproductive hormones. A cross-sectional sample of 589 spouses of pregnant women from Greenland, Poland and Ukraine were enrolled between 2002 and 2004. The men gave semen and blood samples and were interviewed. Six phthalate metabolites of DEHP and DiNP were measured by liquid chromatography tandem mass spectrometry in serum. The metabolites were summed according to their molar weight. We observed significant inverse associations between serum levels of the metabolites, the proxies and serum testosterone. Negative associations were also discovered between some metabolites and sex hormone-binding globulin, semen volume and total sperm count. Findings are compatible with a weak anti-androgenic action of DEHP metabolites, but less so for DiNP metabolites. Metabolic pathways differed significantly between the three study sites, but without major effect on semen quality or reproductive hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Serum Fucosylated Haptoglobin as a Novel Diagnostic Biomarker for Predicting Hepatocyte Ballooning and Nonalcoholic Steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Kamada

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is a growing medical problem around the world. NAFLD patients with nonalcoholic steatohepatitis (NASH can develop cirrhosis and hepatocellular carcinoma. The ability to distinguish NASH from simple steatosis would be of great clinical significance. Ballooning hepatocytes are characteristic of typical pathological NASH; here, the polarized secretion of proteins is disrupted due to destruction of the cytoskeleton. We previously reported that fucosylated glycoproteins are secreted into bile, but not into sera in normal liver. Therefore, we hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes, and serum fucosylated glycoproteins would increase in NASH patients. To confirm our hypothesis, we evaluated serum fucosylated haptoglobin (Fuc-Hpt levels in biopsy-proven NAFLD patients (n = 126 using a lectin-antibody ELISA kit. Fuc-Hpt levels were significantly increased in NASH patients compared with non-NASH (NAFLD patients without NASH patients. Interestingly, Fuc-Hpt levels showed a significant stepwise increase with increasing hepatocyte ballooning scores. Multiple logistic regression analysis showed that Fuc-Hpt levels were independent and significant determinants of the presence of ballooning hepatocytes. Moreover, Fuc-Hpt levels were useful in monitoring liver fibrosis staging. Next, to investigate the significance of serum Fuc-Hpt in a larger population, we measured Fuc-Hpt levels in ultrasound-diagnosed NAFLD subjects (n = 870 who received a medical health checkup. To evaluate NAFLD disease severity, we used the FIB-4 index (based on age, serum AST and ALT levels, and platelet counts. Fuc-Hpt levels increased stepwise with increasing FIB-4 index.Measurement of serum Fuc-Hpt levels can distinguish NASH from non-NASH patients, and predict the presence of ballooning hepatocytes in NAFLD patients with sufficient accuracy. These results support the

  9. Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze.

    Science.gov (United States)

    van der Schee, Marc P; Hashimoto, Simone; Schuurman, Annemarie C; van Driel, Janine S Repelaer; Adriaens, Nora; van Amelsfoort, Romy M; Snoeren, Tessa; Regenboog, Martine; Sprikkelman, Aline B; Haarman, Eric G; van Aalderen, Wim M C; Sterk, Peter J

    2015-02-01

    Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean±sd age 22±9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (prhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthma. Copyright ©ERS 2015.

  10. Clinical Profile and Changes of Serum Lipid Levels in Epileptic Patients after Cerebral Infarction.

    Science.gov (United States)

    Ikeda, Ken; Sawada, Masahiro; Morioka, Harumi; Kyuzen, Maya; Ebina, Junya; Nagasawa, Junpei; Yanagihashi, Masaru; Miura, Ken; Ishikawa, Yuichi; Hirayama, Takehisa; Takazawa, Takanori; Kano, Osamu; Kawabe, Kiyokazu; Iwasaki, Yasuo

    2017-03-01

    Antiepileptic drugs (AEDs) may increase development of dyslipidemia and cerebrovascular disease (CVD). We examined the clinical profile and changes of serum lipid levels after AED monotherapy in patients with poststroke epilepsy (PSE) after cerebral infarction (CI). Medical records were reviewed in consecutive 2144 CI patients. Monotherapy of valproate, carbamazepine (CBZ), phenytoin (PHT), zonisamide, levetiracetam, or lamotrigine was performed in PSE patients. Serum lipid levels were measured before and at 3 months after AED treatment. The prevalence of PSE was 7.0% in CI patients. The TOAST etiology disclosed large-artery atherosclerosis in 68 patients (45%), cardioembolism in 63 patients (42%), and undetermined cause in 19 patients (13%). CVD risk profile showed obesity of 18 patients (12%), current smoker of 30 patients (20%), hypertension of 75 patients (50%), diabetes mellitus of 32 patients (21%), dyslipidemia of 15 patients (10%), and atrial fibrillation of 63 patients (42%). CBZ or PHT administration increased serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels significantly compared to baseline and AED-untreated controls. Those levels were not increased significantly in other AED and control groups. Serum high-density lipoprotein-cholesterol and triglyceride levels did not differ statistically in all groups. The prevalence of post-CI epilepsy was 7.0%. The pathogenesis contributed to atherothrombosis and cardioembolism. CBZ or PHT administration increased serum TC and LDL-C significantly. Thus, we should pay more attention to serum lipid levels in patients receiving cytochrome P450 (CYP)-induced AEDs, and might considerer switching to non-CYP-induced AEDs in patients with unfavorable serum lipid changes. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  11. Comprehensive tumor profiling identifies numerous biomarkers of drug response in cancers of unknown primary site: analysis of 1806 cases.

    Science.gov (United States)

    Gatalica, Zoran; Millis, Sherri Z; Vranic, Semir; Bender, Ryan; Basu, Gargi D; Voss, Andreas; Von Hoff, Daniel D

    2014-12-15

    Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Despite extensive laboratory and imaging efforts, the primary site usually cannot be unequivocally confirmed, and the treatment for the most part remains empirical. Recently, identification of common cancer pathway alterations in diverse cancer lineages has offered an opportunity to provide targeted therapies for patients with CUP, irrespective of the primary site. 1806 cancers of unknown primary were identified among more than 63,000 cases profiled at Caris Life Sciences. Multiplatform profiling of the tumor samples included immunohistochemistry, gene sequencing and in situ hybridization methods in an effort to identify changes in biomarkers that are predictive of drug responses. Biomarkers associated with a potential drug benefit were identified in 96% of cases. Biomarkers identified included those associated with potential benefit in nearly all classes of approved cancer drugs (cytotoxic, hormonal, targeted biological drugs). Additionally, biomarkers associated with a potential lack of benefit were identified in numerous cases, which could further refine the management of patients with CUP. Comprehensive biomarker profiling of CUP may provide additional choices in treatment of patients with these difficult to treat malignancies.

  12. Differential Proteomics Identification of HSP90 as Potential Serum Biomarker in Hepatocellular Carcinoma by Two-dimensional Electrophoresis and Mass Spectrometry

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    Yiyi Sun

    2010-03-01

    Full Text Available The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patients was confirmed using ELISA analysis. The observations suggest that HSP90 might be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of HCC. This work demonstrates that a comprehensive strategy of proteomic identification combined with further validation should be adopted in the field of cancer biomarker discovery.

  13. Amino acid profiles as potential biomarkers for pediatric cancers: a preliminary communication.

    Science.gov (United States)

    Synakiewicz, Anna; Sawicka-Zukowska, Malgorzata; Adrianowska, Natalia; Galezowska, Grazyna; Ratajczyk, Joanna; Owczarzak, Anna; Konieczna, Lucyna; Stachowicz-Stencel, Teresa

    2017-08-03

    Childhood cancer remains one of the main cause of death in the pediatric population. Amino acids (AAs) level alterations in plasma are considered to play a role in carcinogenesis and further course of the disease. Seventy-seven children with cancer, including 47 with hematological and 30 with solid tumors were enrolled in this study and compared with healthy children. Twenty-two plasma-free AAs were determined by HPLC with fluorometric detection. The results revealed significant decrease in glutamine levels for oncological patients and significant increase in aspartic acid, glutamic acid, asparagine, serine, citrulline, alanine, GABA, tryptophan, methionine, valine, phenylalanine and isoleucine levels in cancer children versus control. Plasma-free AA profile as a biomarker, which combines metabolic and clinical data, as an innovative and interdisciplinary approach, may allow for faster detection of tumor occurrence, and in the future for monitoring patient during treatment, and possible prediction of cancer recurrence.

  14. Longitudinal profiles of 15 serum bile acids in patients with intrahepatic cholestasis of pregnancy.

    Science.gov (United States)

    Tribe, Rachel M; Dann, Anthony T; Kenyon, Anna P; Seed, Paul; Shennan, Andrew H; Mallet, Anthony

    2010-03-01

    Increased maternal serum bile acids are implicated in intrahepatic cholestasis of pregnancy. Individual bile acid profiles and their relationship with disease progression, however, remain unknown. The purpose of this prospective study was to determine the temporal changes in bile acids in normal pregnancy and in pregnancies complicated with intrahepatic cholestasis of pregnancy and pruritus gravidarum. A validated method for the evaluation of 15 bile acids (conjugated and unconjugated) in a single serum sample was developed using high-performance liquid chromatography/mass spectrometry (HPLC-MS) with an electrospray interface. Bile acid concentrations were assessed in samples (16 weeks of gestation to 4 weeks postpartum) from women with, or who later developed, intrahepatic cholestasis of pregnancy (n=63) and were compared with those from normal pregnant women (n=26) and from women with pruritus gravidarum (n=43). Intrahepatic cholestasis of pregnancy was associated with a predominant increase in cholic acid conjugated with taurine and glycine, from 24 weeks of pregnancy. Ursodeoxycholic acid (UDCA) treatment (> or =21 days, n=15) significantly reduced serum taurocholic and taurodeoxycholic acid concentrations (Pacid profiles were similar in normal pregnancy and pregnancy associated with pruritus gravidarum. The bile acid profiles and effects of treatment by UDCA implicate a role for taurine-conjugated bile acids in the syndrome of intrahepatic cholestasis of pregnancy. [corrected] With regard to individual bile acid profiles, pruritus gravidarum is a disorder quite distinct from intrahepatic cholestasis of pregnancy.

  15. Neighborhood Socioeconomic Status in Relation to Serum Biomarkers in the Black Women's Health Study.

    Science.gov (United States)

    Cozier, Yvette C; Albert, Michelle A; Castro-Webb, Nelsy; Coogan, Patricia F; Ridker, Paul; Kaufman, Harvey W; Palmer, Julie R; Rosenberg, Lynn

    2016-04-01

    Lower neighborhood socioeconomic status (SES) is associated with higher cardiovascular disease (CVD) risk. Black women have a higher CVD risk and are more likely to live in poor neighborhoods than white women. We examined the association of neighborhood SES with several CVD biomarkers using data from the Black Women's Health Study (BWHS), a follow-up study of US black women reporting high levels of education and income. Blood specimens of 418 BWHS participants were assayed for C-reactive protein (CRP), hemoglobin A1C (hgA1C), and high-density lipoprotein (HDL) cholesterol. US Census block group data were linked to the women's addresses to reflect neighborhood SES. Multivariable-adjusted mixed linear regression models that adjusted for person-level SES and for cardiovascular risk factors were used to assess CRP, hgA1C, and HDL levels in relation to quintiles of neighborhood SES. Women living in the poorest neighborhoods had the least favorable biomarker levels. As neighborhood SES increased, CRP decreased (P for trend = 0.01), hgA1C decreased (P for trend = 0.07), and HDL increased (P for trend = 0.19). These associations were present within strata of individual educational level. The present findings suggest that neighborhood environments may affect physiological processes within residents independently of individual SES.

  16. The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression

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    Farahnaz Ghahremanfard

    2015-09-01

    Full Text Available Objective: Serum lipid levels are not only associated with etiology, but also with prognosis in cancer. To investigate this issue further, we aimed to evaluate the serum levels of lipids in association with the most important prognostic indicators in cancer patients at the start of chemotherapy. Methods: In a retrospective cross-sectional study, using existing medical records obtained from 2009–2014, the data of all incident cancer cases in Iranian patients referred to the Semnan oncology clinic for chemotherapy were analyzed. Data on demographics, cancer type, prognostic indicators (e.g. lymph node involvement, metastasis, and stage of disease, as well as the patient’s lipid profile were collected. We used multiple logistic regression models to show the relationship between prognosis indicators and lipid profile adjusting for age, gender, and type of cancer. Results: The data of 205 patients was gathered. We found a significant difference in the lipid profile between different types of cancers (breast, colon, gastric, and ovarian. With the exception of high-density lipoprotein levels in women, which were higher than in men, the means of other lipid profiles were similar between the genders. There was a significant association between higher levels of low-density lipoprotein (LDL >110mg/dL in the serum and metastasis (adjusted odds ratio=2.4, 95% CI 1.2–3.5. No significant association was reported between lipid profile and lymph nodes involvement and stage of the disease. Conclusion: Our study suggested a benefit of measuring serum levels of lipids for predicting cancer progression. Increased LDL levels can be considered a predictive factor for increasing the risk of metastasis.

  17. Comparison of serum lipid profiles between normal controls and breast cancer patients

    Directory of Open Access Journals (Sweden)

    Pikul Laisupasin

    2013-01-01

    Full Text Available Background: Researchers have reported association of plasma/serum lipids and lipoproteins with different cancers. Increase levels of circulating lipids and lipoproteins have been associated with breast cancer risk. Aim: The aim of this study is to compare serum lipid profiles: total-cholesterol (T-CHOL, triglyceride (TG, high density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and very low density lipoprotein-cholesterol (VLDL-C between breast cancer patients and normal participants. Materials and Methods: A total of 403 women in this study were divided into two groups in the period during May 2006-April 2007. Blood samples were collected from 249 patients with early stage breast cancer and 154 normal controls for serum lipid profiles (T-CHOL, TG, HDL-C, LDL-C and VLDL-C analysis using Hitachi 717 Autoanalyzer (Roche Diagnostic GmbH, Germany. TG, LDL-C and VLDL-C levels in breast cancer group were significantly increased as compared with normal controls group (P < 0.001, whereas HDL-C and T-CHOL levels were not. Results: The results of this study suggest that increased serum lipid profiles may associate with breast cancer risk in Thai women. Further studies to group important factors including, cancer stages, types of cancer, parity, and menopausal status that may affect to lipid profiles in breast cancer patients along with an investigation of new lipid profiles to clarify most lipid factors that may involve in breast cancer development are needed.

  18. Identification of biomarkers that distinguish chemical contaminants based on gene expression profiles.

    Science.gov (United States)

    Wei, Xiaomou; Ai, Junmei; Deng, Youping; Guan, Xin; Johnson, David R; Ang, Choo Y; Zhang, Chaoyang; Perkins, Edward J

    2014-03-31

    High throughput transcriptomics profiles such as those generated using microarrays have been useful in identifying biomarkers for different classification and toxicity prediction purposes. Here, we investigated the use of microarrays to predict chemical toxicants and their possible mechanisms of action. In this study, in vitro cultures of primary rat hepatocytes were exposed to 105 chemicals and vehicle controls, representing 14 compound classes. We comprehensively compared various normalization of gene expression profiles, feature selection and classification algorithms for the classification of these 105 chemicals into14 compound classes. We found that normalization had little effect on the averaged classification accuracy. Two support vector machine (SVM) methods, LibSVM and sequential minimal optimization, had better classification performance than other methods. SVM recursive feature selection (SVM-RFE) had the highest overfitting rate when an independent dataset was used for a prediction. Therefore, we developed a new feature selection algorithm called gradient method that had a relatively high training classification as well as prediction accuracy with the lowest overfitting rate of the methods tested. Analysis of biomarkers that distinguished the 14 classes of compounds identified a group of genes principally involved in cell cycle function that were significantly downregulated by metal and inflammatory compounds, but were induced by anti-microbial, cancer related drugs, pesticides, and PXR mediators. Our results indicate that using microarrays and a supervised machine learning approach to predict chemical toxicants, their potential toxicity and mechanisms of action is practical and efficient. Choosing the right feature and classification algorithms for this multiple category classification and prediction is critical.

  19. Tear Cytokine Profile as a Noninvasive Biomarker of Inflammation for Ocular Surface Diseases: Standard Operating Procedures

    Science.gov (United States)

    Wei, Yi; Gadaria-Rathod, Neha; Epstein, Seth; Asbell, Penny

    2013-01-01

    Purpose. To provide standard operating procedures (SOPs) for measuring tear inflammatory cytokine concentrations and to validate the resulting profile as a minimally invasive objective metric and biomarker of ocular surface inflammation for use in multicenter clinical trials on dry eye disease (DED). Methods. Standard operating procedures were established and then validated with cytokine standards, quality controls, and masked tear samples collected from local and distant clinical sites. The concentrations of the inflammatory cytokines in tears were quantified using a high-sensitivity human cytokine multiplex kit. Results. A panel of inflammatory cytokines was initially investigated, from which four key inflammatory cytokines (IL-1β, IL-6, INF-γ, and TNF-α) were chosen. Results with cytokine standards statistically satisfied the manufacturer's quality control criteria. Results with pooled tear samples were highly reproducible and reliable with tear volumes ranging from 4 to 10 μL. Incorporation of the SOPs into clinical trials was subsequently validated. Tear samples were collected at a distant clinical site, stored, and shipped to our Biomarker Laboratory, where a masked analysis of the four tear cytokines was successfully performed. Tear samples were also collected from a feasibility study on DED. Inflammatory cytokine concentrations were decreased in tears of subjects who received anti-inflammatory treatment. Conclusions. Standard operating procedures for human tear cytokine assessment suitable for multicenter clinical trials were established. Tear cytokine profiling using these SOPs may provide objective metrics useful for diagnosing, classifying, and analyzing treatment efficacy in inflammatory conditions of the ocular surface, which may further elucidate the mechanisms involved in the pathogenesis of ocular surface disease. PMID:24204044

  20. 3D printed conformal microfluidics for isolation and profiling of biomarkers from whole organs.

    Science.gov (United States)

    Singh, Manjot; Tong, Yuxin; Webster, Kelly; Cesewski, Ellen; Haring, Alexander P; Laheri, Sahil; Carswell, Bill; O'Brien, Timothy J; Aardema, Charles H; Senger, Ryan S; Robertson, John L; Johnson, Blake N

    2017-07-25

    The ability to interface microfluidic devices with native complex biological architectures, such as whole organs, has the potential to shift the paradigm for the study and analysis of biological tissue. Here, we show 3D printing can be used to fabricate bio-inspired conformal microfluidic devices that directly interface with the surface of whole organs. Structured-light scanning techniques enabled the 3D topographical matching of microfluidic device geometry to porcine kidney anatomy. Our studies show molecular species are spontaneously transferred from the organ cortex to the conformal microfluidic device in the presence of fluid flow through the organ-conforming microchannel. Large animal studies using porcine kidneys (n = 32 organs) revealed the profile of molecular species in the organ-conforming microfluidic stream was dependent on the organ preservation conditions. Enzyme-linked immunosorbent assay (ELISA) studies revealed conformal microfluidic devices isolate clinically relevant metabolic and pathophysiological biomarkers from whole organs, including heat shock protein 70 (HSP-70) and kidney injury molecule-1 (KIM-1), which were detected in the microfluidic device as high as 409 and 12 pg mL-1, respectively. Overall, these results show conformal microfluidic devices enable a novel minimally invasive 'microfluidic biopsy' technique for isolation and profiling of biomarkers from whole organs within a clinically relevant interval. This achievement could shift the paradigm for whole organ preservation and assessment, thereby helping to relieve the organ shortage crisis through increased availability and quality of donor organs. Ultimately, this work provides a major advance in microfluidics through the design and manufacturing of organ-conforming microfluidic devices and a novel technique for microfluidic-based analysis of whole organs.

  1. Two dimensional gel electrophoresis using narrow pH 3-5.6 immobilised pH gradient strips identifies potential novel disease biomarkers in plasma or serum

    OpenAIRE

    sprotocols

    2015-01-01

    Authors: Bevin Gangadharan & Nicole Zitzmann ### Abstract Two-dimensional gel electrophoresis (2-DE) is a protein separation technique often used to separate plasma or serum proteins in an attempt to identify novel biomarkers. This protocol describes how to run 2-DE gels using narrow pH 3-5.6 immobilised pH gradient strips to separate 2 mg of serum proteins. pH 3-6 ampholytes are used to enhance the solubility of proteins in this pH range before the serum proteins are separated in...

  2. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.; Hoogland, Marije; Vredenbregt-van den Berg, Mirella S.; Willemsen, Rob; Luider, Theo N.; Pasa-Tolic, Ljiljana; Jenster, Guido

    2013-12-31

    Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between

  3. Selected serum oxidative stress biomarkers in dogs with non-food-induced and food-induced atopic dermatitis.

    Science.gov (United States)

    Almela, Ramón M; Rubio, Camila P; Cerón, José J; Ansón, Agustina; Tichy, Alexander; Mayer, Ursula

    2018-02-01

    Oxidative stress (OS) has been shown to be involved in the pathogenesis of human and canine atopic dermatitis (AD) through several distinct mechanisms. Selected serum biomarkers of OS (sbOS) have been validated in normal dogs and studied in several canine diseases. To the best of the authors' knowledge, the sbOS evaluated in this study have not previously been described in canine AD. The aims of the study were to evaluate a panel of sbOS in dogs with food-induced (FIAD) and non-food-induced (NFIAD) AD: cupric reducing antioxidant capacity (CUPRAC), ferrous oxidation-xylenol orange (FOX), ferric reducing ability of the plasma (FRAP), paraoxonase-1 (PON1), trolox equivalent antioxidant capacity (TEAC) and serum total thiol (THIOL). The aim was to compare these metabolites with those in healthy control dogs, and to correlate sbOS with validated pruritus and CADESI-04 severity scales in dogs with AD. Forty six healthy, nine NFIAD and three FIAD client-owned dogs were included. The study was designed as a cohort study. There were significant differences in atopic dogs when compared to healthy dogs for all of the sbOS analysed. These findings suggest that OS could play a role in the pathogenesis of canine NFIAD and FIAD. In addition, the evaluation of sbOS could be useful for precision medicine to help to detect atopic dogs that might benefit from antioxidant-targeted therapies. © 2018 ESVD and ACVD.

  4. Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock

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    Min-Yi Huang

    2016-01-01

    Full Text Available We evaluated the tendency of the plasma concentration and procalcitonin (PCT clearance (PCTc to act as biomarkers of prognosis in patients with severe sepsis and septic shock. From 2011 to 2013, we prospectively analyzed patients with sepsis admitted to the intensive care unit (ICU. The serum PCT was evaluated at the time of sepsis diagnosis and again after 48 h (day 3 and 96 h (day 5. PCTc after 48 h (PCTc-day 3 and 96 h (PCTc-day 5 was also calculated to evaluate the prognostic value for survival in patients with sepsis. A total of 48 patients were included. Overall mortality was 16.7% (8 patients. PCTc was higher in survivors than in nonsurvivors, with significant differences on day 3 and day 5 (p=0.033; p=0.002, resp.; however, serum PCT levels on day 1, day 3, and day 5 were not significant prognostic factors for survival. The prognosis of patients with severe sepsis and septic shock may be associated with PCTc. Dynamic changes of PCT reflected as PCTc at 48 h (day 3 and 96 h (day 5 after admission to the ICU may serve as a predictor of survival in critically ill patients with severe sepsis.

  5. Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.

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    Naduparambil Korah Jacob

    Full Text Available Exposure to ionizing radiation through environmental, occupational or a nuclear reactor accident such as the recent Fukushima Daiichi incident often results in major consequences to human health. The injury caused by radiation can manifest as acute radiation syndromes within weeks in organs with proliferating cells such as hematopoietic and gastrointestinal systems. Cancers, fibrosis and degenerative diseases are also reported in organs with differentiated cells, months or years later. Studies conducted on atom bomb survivors, nuclear reactor workers and animal models have shown a direct correlation of these effects with the absorbed dose. Physical dosimeters and the available radio-responsive biologics in body fluids, whose responses are rather indirect, have limitations to accurately evaluate the extent of post exposure damage. We have used an amplification-free, hybridization based quantitative assay utilizing the nCounter multiplex platform developed by nanoString Technologies to compare the levels of over 600 miRNAs in serum from mice irradiated at a range of 1 to 12 Gy at 24 and 48 hr time points. Development of a novel normalization strategy using multiple spike-in oligonucleotides allowed accurate measurement of radiation dose and time dependent changes in serum miRNAs. The response of several evolutionarily conserved miRNAs abundant in serum, were found to be robust and sensitive in the dose range relevant for medical triage and in patients who receive total body radiation as preparative regimen for bone marrow transplantation. Notably, miRNA-150, abundant in lymphocytes, exhibited a dose and time dependent decrease in serum, which we propose as a sensitive marker indicative of lymphocyte depletion and bone marrow damage. Our study has identified several markers useful for evaluation of an individual's response by minimally invasive methods, relevant to triage in case of a radiation accident and evaluation of toxicity and response

  6. Serum Cytokines as Biomarkers in Islet Cell Transplantation for Type 1 Diabetes.

    Science.gov (United States)

    van der Torren, Cornelis R; Verrijn Stuart, Annemarie A; Lee, DaHae; Meerding, Jenny; van de Velde, Ursule; Pipeleers, Daniel; Gillard, Pieter; Keymeulen, Bart; de Jager, Wilco; Roep, Bart O

    2016-01-01

    Islet cell transplantation holds a potential cure for type 1 diabetes, but many islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of islet transplantation. Thirteen islet transplant patients were selected on basis of good graft function (reaching insulin independence) or insufficient engraftment (insulin requiring) from our cohort receiving standardized grafts and immune suppressive therapy. Patients reaching insulin independence were divided in those with continued (>12 months) versus transient (cytokines and adipokines was measured in sera taken before and at one year after transplantation using a validated multiplex immunoassay platform. Ninety serum proteins were detectable in concentrations varying markedly among patients at either time point. Thirteen markers changed after transplantation, while another seven markers changed in a clinical subpopulation. All other markers remained unaffected after transplantation under generalized immunosuppression. Patterns of cytokines could distinguish good graft function from insufficient function including IFN-α, LIF, SCF and IL-1RII before and after transplantation, by IL-16, CCL3, BDNF and M-CSF only before and by IL-22, IL-33, KIM-1, S100A12 and sCD14 after transplantation. Three other proteins (Leptin, Cathepsin L and S100A12) associated with loss of temporary graft function before or after transplantation. Distinct cytokine signatures could be identified in serum that predict or associate with clinical outcome. These serum markers may help guiding patient selection and choice of immunotherapy, or act as novel drug targets in islet transplantation.

  7. Correlation of various serum biomarkers with the severity of diabetic retinopathy.

    Science.gov (United States)

    Nalini, M; Raghavulu, B V; Annapurna, A; Avinash, P; Chandi, Vishala; Swathi, N; Wasim

    2017-11-01

    Hyperglycemia induced inflammation and angiogenic factors are implicated as a contributor to the onset and progression of diabetic retinopathy (DR) in type 2 diabetes mellitus patients (T2DM). Tumor necrosis factor (TNF-alpha) and C-reactive protein (CRP) are inflammatory cytokines which induce retinal VEGF and are involved in the progression of proliferative diabetic retinopathy (PDR). Therefore the aim of the present study is to investigate the relationship between diabetic retinopathy and systemic inflammation in patients with type 2 diabetes mellitus. Patients with T2DM, with or without diabetic retinopathy were included in the study. Serum inflammatory cytokines, vascular growth factor were studied in different stages of DR. Patients with T2DM with and without diabetic retinopathy were compared. Patients with diabetic retinopathy had increased serum levels of inflammatory cytokines CRP, TNF-alpha, as well as VEGF compared to serum levels of diabetic patients without retinopathy. T2DM patients with retinopathy have higher levels of circulating inflammatory cytokines and VEGF compared to patients without retinopathy. These proinflammatory cytokines and angiogenic factors are involved in the progression of DR and proliferative diabetic retinopathy. The results showed the importance of inflammation and vascular endothelial growth factor in the progression of NPDR and PDR. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  8. Discovery of gastric cancer specific biomarkers by the application of serum proteomics.

    Science.gov (United States)

    Yoo, Moon-Won; Park, Jisook; Han, Hye-Seung; Yun, Yeo-Min; Kang, Jeong Won; Choi, Do-Young; Lee, Joon Won; Jung, Jae Hun; Lee, Kyung-Yung; Kim, Kwang Pyo

    2017-03-01

    Current diagnostic markers for gastric cancer are not sufficiently specific or sensitive for use in clinical practice. The aims of this study are to compare the proteomes of serum samples from patients with gastric cancers and normal controls, and to develop useful tumor markers of gastric cancer by quantitative proteomic analysis. We identified a total of 388 proteins with a ≤1% FDR and with at least two unique peptides from the sera of each group. Among them, 215, 251, and 260 proteins were identified in serum samples of patients in an advanced cancer group, early cancer group, and normal control group, respectively. We selected differentially expressed proteins in cancer patients compared with those of normal controls via semiquantitative analyses comparing the spectral counts of identified proteins. These differentially expressed proteins were successfully verified using an MS-based quantitative assay, multiple reactions monitoring analysis. Four proteins (vitronectin, clusterin isoform 1, thrombospondin 1, and tyrosine-protein kinase SRMS) were shown to have significant changes between the cancer groups and the normal control group. These four serum proteins were able to discriminate gastric cancer patients from normal controls with sufficient specificity and selectivity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. The sitting position during neurosurgical procedures does not influence serum biomarkers of pulmonary parenchymal injury

    Directory of Open Access Journals (Sweden)

    Duda Izabela

    2012-12-01

    Full Text Available Abstract Background The sitting position during neurosurgical operations predisposes to air penetration through veins and the movement of the air through the pulmonary circulation. Contact of an air bubble with the endothelium can lead to acute lung injury. The presence of specific pulmonary proteins in the plasma such as surfactant protein D (SP-D and Clara cell protein (CC16 is a biomarker of damaging processes at the air-blood barrier. The aim of our study was to examine the hypothesis that the level of investigated pulmonary biomarkers in plasma is higher in patients operated on in the sitting position. Methods The study included patients undergoing planned neurosurgical operations, who were divided into two groups: the sitting group (40 patients, operated on in the sitting position and the supine group (24 patients, operated in the supine position. After the operation blood samples were drawn, centrifuged, frozen and stored until analyses were conducted. The determination of the SP-D and CC16 levels was performed using an ELISA test. Air embolism (VAE was defined as a sudden drop in etCO2 of more than 2 mmHg and the presence of air bubbles in the aspirated blood from the central cannula. In all patients, the number of hospitalization days in the postoperative period was calculated. Results There were no differences in the average levels of SP-D between the groups (the mean in the sitting group was 95.56 ng/mL and the mean in the supine group was 101.21 ng/mL. The average levels of CC16 were similar in both groups as well (6.56ng/mL in the sitting group and 6.79ng/mL in the supine group. There was a statistically significant positive correlation between SP-D and CC16 values in both groups. VAE was diagnosed clinically in 12.5% of cases in the sitting group without a significant increase in SP-D and CC16 levels. On average, patients in both groups were discharged from the hospital within 9 days of surgery. Conclusion The sitting position and

  10. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Laarakkers, Coby M. M.; van der Kuur, Ellen C.; Morava-Kozicz, Eva; Wevers, Ron A.; Augustijn, Kevin D.; Touw, Daan J.; Sandel, Maro H.; Masereeuw, Rosalinde; Russel, Frans G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

  11. Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.

    Science.gov (United States)

    Ghareghani, Majid; Dokoohaki, Shima; Ghanbari, Amir; Farhadi, Naser; Zibara, Kazem; Khodadoust, Saeid; Parishani, Mohammad; Ghavamizadeh, Mehdi; Sadeghi, Heibatollah

    2017-01-01

    Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations. © 2016 John Wiley & Sons Australia, Ltd.

  12. Dietary fiber intake and its association with indicators of adiposity and serum biomarkers in European adolescents: the HELENA study.

    Science.gov (United States)

    Lin, Yi; Huybrechts, Inge; Vereecken, Carine; Mouratidou, Theodora; Valtueña, Jara; Kersting, Mathilde; González-Gross, Marcela; Bolca, Selin; Wärnberg, Julia; Cuenca-García, Magdalena; Gottrand, Frederic; Toti, Elisabetta; Gomez-Martínez, Sonia; Grammatikaki, Evangelia; Labayen, Idoia; Moreno, Luis A; Sjöström, Michael; Van Camp, John; Roccaldo, Romana; Patterson, Emma; Manios, Yannis; Molnar, Denes; Kafatos, Anthony; Widhalm, Kurt; De Henauw, Stefaan

    2015-08-01

    To evaluate total, energy-adjusted dietary fiber (DF), water-soluble fiber (WSF), and water-insoluble fiber (WIF) intakes in European adolescents and to investigate their association with indicators of adiposity and serum biomarkers. This study, conducted from 2006 to 2007, included 1804 adolescents aged 12.5-17.5 years (47% males) from eight European cities completing two non-consecutive computerized 24-h dietary recalls. GLM multivariate analysis was used to investigate associations. Mean DF intake (20 g/day) of the sample met the European Food Safety Authority recommendation, but was below those of the World Health Organization and of the Institute of Medicine. Total DF, WSF and WIF intakes were higher in males (P < 0.001), but following energy-adjustments significantly higher intakes were observed among females (P < 0.001). Bread and cereals contributed most to total DF, WSF and WIF intakes, followed by potatoes and grains, energy-dense but low-nutritious foods, fruits and vegetables. Moreover, energy-adjusted WSF and WIF were positively associated with body fat percentage (BF%), waist to height ratio and low-density lipoprotein cholesterol, while energy-adjusted WSF was inversely associated with serum fasting glucose (β = -0. 010, P = 0.020). Total DF intakes are rather low in European adolescents. An inverse association with serum fasting glucose might indicate a possible beneficial role of DF in preventing insulin resistance and its concomitant diseases, even though DF intakes were positively associated with adolescents' BF%. Therefore, further longitudinal studies should elaborate on these potential beneficial effects of DF intake in the prevention of obesity and related chronic diseases.

  13. Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

    Science.gov (United States)

    Ferreira, Cláudia N; Carvalho, Maria G; Reis, Helton J; Gomes, Karina B; Sousa, Marinez O; Palotás, András

    2014-05-01

    Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

  14. Serum protein profiles predict coronary artery disease in symptomatic patients referred for coronary angiography

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    LaFramboise William A

    2012-12-01

    Full Text Available Abstract Background More than a million diagnostic cardiac catheterizations are performed annually in the US for evaluation of coronary artery anatomy and the presence of atherosclerosis. Nearly half of these patients have no significant coronary lesions or do not require mechanical or surgical revascularization. Consequently, the ability to rule out clinically significant coronary artery disease (CAD using low cost, low risk tests of serum biomarkers in even a small percentage of patients with normal coronary arteries could be highly beneficial. Methods Serum from 359 symptomatic subjects referred for catheterization was interrogated for proteins involved in atherogenesis, atherosclerosis, and plaque vulnerability. Coronary angiography classified 150 patients without flow-limiting CAD who did not require percutaneous intervention (PCI while 209 required coronary revascularization (stents, angioplasty, or coronary artery bypass graft surgery. Continuous variables were compared across the two patient groups for each analyte including calculation of false discovery rate (FDR ≤ 1% and Q value (P value for statistical significance adjusted to ≤ 0.01. Results Significant differences were detected in circulating proteins from patients requiring revascularization including increased apolipoprotein B100 (APO-B100, C-reactive protein (CRP, fibrinogen, vascular cell adhesion molecule 1 (VCAM-1, myeloperoxidase (MPO, resistin, osteopontin, interleukin (IL-1β, IL-6, IL-10 and N-terminal fragment protein precursor brain natriuretic peptide (NT-pBNP and decreased apolipoprotein A1 (APO-A1. Biomarker classification signatures comprising up to 5 analytes were identified using a tunable scoring function trained against 239 samples and validated with 120 additional samples. A total of 14 overlapping signatures classified patients without significant coronary disease (38% to 59% specificity while maintaining 95% sensitivity for patients requiring

  15. Serum IgE reactivity profiling in an asthma affected cohort.

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    Tania Dottorini

    Full Text Available BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09. An artificial neural network (ANN-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile.

  16. Cerebrospinal fluid and serum cytokine profiles in narcolepsy with cataplexy: a case-control study.

    Science.gov (United States)

    Dauvilliers, Yves; Jaussent, Isabelle; Lecendreux, Michel; Scholz, Sabine; Bayard, Sophie; Cristol, Jean Paul; Blain, Hubert; Dupuy, Anne-Marie

    2014-03-01

    Recent advances in the identification of susceptibility genes and environmental exposures provide strong support that narcolepsy-cataplexy is an immune-mediated disease. Only few serum cytokine studies with controversial results were performed in narcolepsy and none in the cerebrospinal fluid. We measured a panel of 12 cytokines by a proteomic approach in the serum of 35 patients with narcolepsy-cataplexy compared to 156 healthy controls, and in the cerebrospinal fluid of 34 patients with narcolepsy-cataplexy compared to 17 non-narcoleptic patients; and analyzed the effect of age, duration and severity of disease on the cytokine levels. After multiple adjustments we reported lower serum IL-2, IL-8, TNF-α, MCP-1 and EGF levels, and a tendency for higher IL-4 level in narcolepsy compared to controls. Significant differences were only found for IL-4 in cerebrospinal fluid, being higher in narcolepsy. Positive correlations were found in serum between IL-4, daytime sleepiness, and cataplexy frequency. The expression of some pro-inflammatory cytokines (MCP-1, VEGF, EGF, IL2, IL-1β, IFN-γ) in either serum or CSF was negatively correlated with disease severity and duration. No correlation was found for any specific cytokine in 18 of the patients with narcolepsy with peripheral and central samples collected the same day. Significant decreased pro/anti-inflammatory cytokine profiles were found at peripheral and central levels in narcolepsy, together with a T helper 2/Th1 serum cytokine secretion imbalance. To conclude, we showed some evidence for alterations in the cytokine profile in patients with narcolepsy-cataplexy compared to controls at peripheral and central levels, with the potential role of IL-4 and significant Th1/2 imbalance in the pathophysiology of narcolepsy. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Alteration of serum lipid profile and its prognostic value in head and neck squamous cell carcinoma.

    Science.gov (United States)

    Li, Gang; Da, Mingjie; Zhang, Wei; Wu, Heming; Ye, Jinhai; Chen, Jie; Ma, Lu; Gu, Ning; Wu, Yunong; Song, Xiaomeng

    2016-03-01

    Several serum lipid components have been implicated in the development of cancer. However, the prognostic significance of serum lipid components in head and neck squamous cell carcinoma is unknown. Here, we investigated the predictive value of serum lipid profile at diagnosis and in the overall survival of the patients. The study population consists of 136 pathologically confirmed head and neck squamous cell carcinoma cases diagnosed between years 2009 and 2014 at a tertiary medical center. Levels of preoperative serum lipid component's total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were compared between patients and normal controls matched for age and gender. Serum lipid profiles and their association with clinical parameters were analyzed. The effects of the serum lipid components on survival were examined using the proportional hazards regression model to estimate hazard ratio. Significant lower levels of cholesterol, low-density lipoprotein, apolipoprotein A, and apolipoprotein B were found in patients with oral cancer (P < 0.0001). However, a significantly higher level of lipoprotein (a) was found in the cancer group (P < 0.0001). Patients with higher lipoprotein (a) had significantly shorter overall survival than those with lower lipoprotein (a) (P = 0.0042). Multivariate analysis showed that both higher lipoprotein (a) and lymph node metastasis are independent prognostic factors in the patient population (P < 0.01). A higher lipoprotein (a) was associated with poorer prognosis and might be a novel marker in patients with head and neck squamous cell carcinoma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Serum fatty acid, lipid profile and dietary intake of Hong Kong Chinese omnivores and vegetarians.

    Science.gov (United States)

    Lee, H Y; Woo, J; Chen, Z Y; Leung, S F; Peng, X H

    2000-10-01

    To examine the serum fatty acid and lipid profiles and dietary intake of Hong Kong Chinese omnivores and vegetarians with respect to cardiovascular health. Random population survey stratified by age and sex. One-hundred and ninety-four omnivore subjects (81 men, 113 women) age 25-70 y, and 60 ovo-lacto-vegetarian adults (15 men, 45 women) age 30-55 y. Nutrient quantitation was by a food frequency method. Serum fatty acids were analysed by gas chromatography, and serum lipid by standard laboratory methods. Compared with omnivores, vegetarians had higher serum concentrations of polyunsaturated (PUFA) and monosaturated fatty acids (MUFA), and lower saturated fatty acids (SFA), long chain omega-3 and trans fatty acids (TFA). They also had lower serum cholesterol and higher apoA-1 concentrations, but the LDL/HDL ratio was not different. The ratio of polyunsaturated to saturated fatty acids intake was higher in vegetarians. Compared with results from populations with higher incidences of coronary heart disease, while lower myristic and palmitic acid concentrations and higher eicosapentaneoic (EPA) and docosahexanoic acid (DHA) may partly account for the difference in incidence, linoleic acid concentration was higher. Although the Chinese vegetarian diet may be beneficial for heart health in that antioxidant and fibre intakes are higher and saturated fat lower, the low EPA and DHA due to omission from dietary source and suppressed formation by high linoleic acid level, and the presence of TFA in the diet, may exert an opposite effect. There are some favourable features in the serum fatty acid profile in the Hong Kong Chinese population with respect to cardiovascular health, but the consumption of TFA is of concern. The Chinese vegetarian diet also contains some adverse features.

  19. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

    LENUS (Irish Health Repository)

    Rooney, Terence

    2012-02-01

    OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

  20. Serum biochemical profile in senepol calves at the first 120 days of age

    Directory of Open Access Journals (Sweden)

    Jéssica Lawanne Delfino

    2014-06-01

    Full Text Available The serum biochemical values allow to establish reference used in metabolic and clinical evaluations of calves, reducing losses in cattle breeding. The aim of this study was to evaluate the influence of age on serum biochemical profile in Senepol calves, at the first 120 days of age. The experiment was conducted in the city of Uberlândia, Minas Gerais, Brazil, in four periods after birth (0-15, 30, 60 and 120 days of age. Blood samples were obtained by jugular venipuncture for determination of serum total protein, albumin, globulin, triglycerides, cholesterol, AST, GGT, FA, calcium, phosphorus, magnesium, creatinine and urea. Cholesterol remained at minimum reference values or below throughout the experiment. Animals at 30 days showed the lowest values of protein concentrations, minerals and triglycerides that normalized up to 60 days of life, except to albumin that slower recovery was showed. Our data showed that the serum biochemical profile in Senepol is influenced by age up to 120 days of age; moreover there are differences with other breeds.

  1. Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease

    Science.gov (United States)

    Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

    2015-01-01

    Abstract Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral–genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage. The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity. We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay. Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC. Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis. PMID:26496336

  2. Preoperative serum cystatin-C as a potential biomarker for prognosis of renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Shengjie Guo

    Full Text Available The prognostic value of serum cystatin-C (Cys-C in renal cell carcinoma (RCC remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients.The levels of preoperative Cys-C, creatinine (CRE and estimated glomerular filtration rate (e-GFR were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC.Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L was significantly associated with shorter overall survival (OS in all RCC patients (hazard ratio [HR], 1.59; P = 0.012, patients at pT1-2 (P<0.001, pN0 (P<0.001 and pM0 stages (P<0.001. Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS (HR, 3.50; P = 0.013.An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up.

  3. A systematic review and meta-analysis of diagnostic and prognostic serum biomarkers of colorectal cancer.

    Science.gov (United States)

    Liu, Zhongyu; Zhang, Yingchong; Niu, Yulong; Li, Ke; Liu, Xin; Chen, Huijuan; Gao, Chunfang

    2014-01-01

    Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). The databases MEDLINE and EMBASE were searched iteratively to identify the relevant literature for serum markers of CRC published from 1950 to August 2012. The articles that provided adequate information to meet the requirements of the meta-analysis of diagnostic and prognostic markers were included. A 2-by-2 table of each diagnostic marker and its hazard ratio (HR) and the confidence interval (CI) of each prognostic marker was directly or indirectly extracted from the included papers, and the pooled sensitivity and specificity of the diagnostic marker and the pooled HR and the CI of the prognostic marker were subsequently calculated using the extracted data. In total, 104 papers related to the diagnostic markers and 49 papers related to the prognostic serum markers of CRC were collected, and only 19 of 92 diagnostic markers were investigated in more than two studies, whereas 21 out of 44 prognostic markers were included in two or more studies. All of the pooled sensitivities of the diagnostic markers with > = 3 repetitions were less than 50%, and the meta-analyses of the prognostic markers with more than 3 studies were performed, VEGF with highest (2.245, CI: 1.347-3.744) and MMP-7 with lowest (1.099, CI: 1.018-1.187)) pooled HRs are presented. The quality of studies addressing the diagnostic and prognostic accuracy of the tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice.

  4. Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease.

    Science.gov (United States)

    Lopalco, Giuseppe; Lucherini, Orso Maria; Vitale, Antonio; Talarico, Rosaria; Lopalco, Antonio; Galeazzi, Mauro; Lapadula, Giovanni; Cantarini, Luca; Iannone, Florenzo

    2015-10-01

    Behcet's disease (BD) is a multisystemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of vascular, gastrointestinal, neurological, and musculoskeletal system. Although disease pathogenesis is still unclear, both innate and adaptive immunity have shown to play a pivotal role, and multiple proinflammatory cytokines seem to be involved in different pathogenic pathways that eventually lead to tissue damage.The aims of our study were to evaluate serum cytokines levels of IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, CXCL9, and SAA levels in patients with BD, in comparison to healthy controls (HC), and to correlate their levels to disease activity.We included 78 serum samples obtained from 58 BD patients and analyzed a set of proinflammatory cytokines including IL-8, IL-18, IFN-α2a, IL-6, IFN-γ, CXCL10, CXCL11, and CXCL9 by multiplex bead analysis as well as SAA by enzyme-linked immunosorbent assay.Compared to HC, BD patients showed elevated cytokine levels of IL-8, IL-18, IFN-α2a, and IL-6, and low levels of CXCL11. BD patients with SAA serum levels >20 mg/L showed higher levels of proinflammatory markers than HC or group with SAA ≤20 mg/L. IL-18, IFN-α2a, and IL-6 were higher in BD group with SAA >20 mg/L than HC, while IL-8 and CXCL9 levels were higher than in patients with SAA ≤20 mg/L and HC.Active BD patients with SAA >20 mg/L exhibited elevated levels of inflammatory mediators, suggesting that may exist a relationship between SAA and proinflammatory cytokines in the intricate scenario of BD pathogenesis.

  5. Preoperative serum cystatin-C as a potential biomarker for prognosis of renal cell carcinoma.

    Science.gov (United States)

    Guo, Shengjie; Xue, Yunfei; He, Qiuming; He, Xiaobo; Guo, Kunbin; Dong, Pei; Yao, Kai; Yang, Guangwei; Chen, Dong; Li, Zaishang; Li, Xiangdong; Qin, Zike; Liu, Zhuowei; Cheng, Wenjie; Guo, Chao; Zhang, Meng; Han, Hui; Zhou, Fangjian

    2017-01-01

    The prognostic value of serum cystatin-C (Cys-C) in renal cell carcinoma (RCC) remains unknown. The purpose of this study is to explore the prognostic value of Cys-C for RCC patients. The levels of preoperative Cys-C, creatinine (CRE) and estimated glomerular filtration rate (e-GFR) were retrospectively collected in 325 RCC patients undergoing surgery. The cutoff values of Cys-C, CRE and e-GFR were determined by the standardized Cutoff Finder algorithm. The receiver operating characteristic (ROC) curve and pairwise comparison were performed to compare the three variables. Univariate and multivariate Cox regression analyses were performed to investigate the prognostic value of serum Cys-C in RCC. Based on the analysis of Cutoff Finder algorithm, ROC curve and pairwise comparison, the preoperative Cys-C was superior to CRE and e-GFR as a predictive factor in RCC. Multivariate Cox regression analyses showed that high preoperative Cys-C (>1.09 mg/L) was significantly associated with shorter overall survival (OS) in all RCC patients (hazard ratio [HR], 1.59; P = 0.012), patients at pT1-2 (P<0.001), pN0 (P<0.001) and pM0 stages (P<0.001). Moreover, Multivariate Cox regression analyses also showed that in the 306 patients without metastasis, high preoperative Cys-C was also associated with shorter disease-free survival (DFS) (HR, 3.50; P = 0.013). An elevated preoperative Cys-C level was demonstrated to be related with worse survival in patients with RCC. Measuring preoperative serum Cys-C might be a simple way for finding poor prognostic patients and patients with elevated preoperative Cys-C level should be more closely followed up.

  6. Quantification of a cardiac biomarker in human serum using extraordinary optical transmission (EOT.

    Directory of Open Access Journals (Sweden)

    Tao Ding

    Full Text Available Nanoimprinting lithography (NIL is a manufacturing process that can produce macroscale surface areas with nanoscale features. In this paper, this technique is used to solve three fundamental issues for the application of localized surface plasmonic resonance (LSPR in practical clinical measurements: assay sensitivity, chip-to-chip variance, and the ability to perform assays in human serum. Using NIL, arrays of 140 nm square features were fabricated on a sensing area of 1.5 mm x 1.5 mm with low cost. The high reproducibility of NIL allowed for the use of a one-chip, one-measurement approach with 12 individually manufactured surfaces with minimal chip-to-chip variations. To better approximate a real world setting, all chips were modified with a biocompatible, multi-component monolayer and inter-chip variability was assessed by measuring a bioanalyte standard (2.5-75 ng/ml in the presence of a complex biofluid, human serum. In this setting, nanoimprinted LSPR chips were able to provide sufficient characteristics for a 'low-tech' approach to laboratory-based bioanalyte measurement, including: 1 sufficient size to interface with a common laboratory light source and detector without the need for a microscope, 2 high sensitivity in serum with a cardiac troponin limit of detection of 0.55 ng/ml, and 3 very low variability in chip manufacturing to produce a figure of merit (FOM of 10.5. These findings drive LSPR closer to technical comparability with ELISA-based assays while preserving the unique particularities of a LSPR based sensor, suitability for multiplexing and miniaturization, and point-of-care detections.

  7. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus.

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    Chaojun Hu

    Full Text Available Autoantibodies in cerebrospinal fluid (CSF from patients with neuropsychiatric systemic lupus erythematosus (NPSLE may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosuspatients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43.Anti-proliferating cell nuclear antigen (PCNA was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A. The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045.Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009. Analysis with Spearman's rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE.

  8. Least absolute shrinkage and selection operator type methods for the identification of serum biomarkers of overweight and obesity: simulation and application

    Directory of Open Access Journals (Sweden)

    Monica M. Vasquez

    2016-11-01

    Full Text Available Abstract Background The study of circulating biomarkers and their association with disease outcomes has become progressively complex due to advances in the measurement of these biomarkers through multiplex technologies. The Least Absolute Shrinkage and Selection Operator (LASSO is a data analysis method that may be utilized for biomarker selection in these high dimensional data. However, it is unclear which LASSO-type method is preferable when considering data scenarios that may be present in serum biomarker research, such as high correlation between biomarkers, weak associations with the outcome, and sparse number of true signals. The goal of this study was to compare the LASSO to five LASSO-type methods given these scenarios. Methods A simulation study was performed to compare the LASSO, Adaptive LASSO, Elastic Net, Iterated LASSO, Bootstrap-Enhanced LASSO, and Weighted Fusion for the binary logistic regression model. The simulation study was designed to reflect the data structure of the population-based Tucson Epidemiological Study of Airway Obstructive Disease (TESAOD, specifically the sample size (N = 1000 for total population, 500 for sub-analyses, correlation of biomarkers (0.20, 0.50, 0.80, prevalence of overweight (40% and obese (12% outcomes, and the association of outcomes with standardized serum biomarker concentrations (log-odds ratio = 0.05–1.75. Each LASSO-type method was then applied to the TESAOD data of 306 overweight, 66 obese, and 463 normal-weight subjects with a panel of 86 serum biomarkers. Results Based on the simulation study, no method had an overall superior performance. The Weighted Fusion correctly identified more true signals, but incorrectly included more noise variables. The LASSO and Elastic Net correctly identified many true signals and excluded more noise variables. In the application study, biomarkers of overweight and obesity selected by all methods were Adiponectin, Apolipoprotein H, Calcitonin, CD

  9. Effects of a honeybee sting on the serum free amino acid profile in humans.

    Directory of Open Access Journals (Sweden)

    Jan Matysiak

    Full Text Available The aim of this study was to assess the response to a honeybee venom by analyzing serum levels of 34 free amino acids. Another goal of this study was to apply complex analytic-bioinformatic-clinical strategy based on up-to-date achievements of mass spectrometry in metabolomic profiling. The amino acid profiles were determined using hybrid triple quadrupole/linear ion trap mass spectrometer coupled with a liquid chromatography instrument. Serum samples were collected from 27 beekeepers within 3 hours after they were stung and after a minimum of 6 weeks following the last sting. The differences in amino acid profiles were evaluated using MetaboAnalyst and ROCCET web portals. Chemometric tests showed statistically significant differences in the levels of L-glutamine (Gln, L-glutamic acid (Glu, L-methionine (Met and 3-methyl-L-histidine (3MHis between the two analyzed groups of serum samples. Gln and Glu appeared to be the most important metabolites for distinguishing the beekeepers tested shortly after a bee sting from those tested at least 6 weeks later. The role of some amino acids in the response of an organism to the honeybee sting was also discussed. This study indicated that proposed methodology may allow to identify the individuals just after the sting and those who were stung at least 6 weeks earlier. The results we obtained will contribute to better understanding of the human body response to the honeybee sting.

  10. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Xue Zhao

    2016-01-01

    Full Text Available A growing body of evidence has shown the intimate relationship between metabolomic profiles and insulin resistance (IR in obese adults, while little is known about childhood obesity. In this review, we searched available papers addressing metabolomic profiles and IR in obese children from inception to February 2016 on MEDLINE, Web of Science, the Cochrane Library, ClinicalTrials.gov, and EMASE. HOMA-IR was applied as surrogate markers of IR and related metabolic disorders at both baseline and follow-up. To minimize selection bias, two investigators independently completed this work. After critical selection, 10 studies (including 2,673 participants were eligible and evaluated by using QUADOMICS for quality assessment. Six of the 10 studies were classified as “high quality.” Then we generated all the metabolites identified in each study and found amino acid metabolism and lipid metabolism were the main affected metabolic pathways in obese children. Among identified metabolites, branched-chain amino acids (BCAAs, aromatic amino acids (AAAs, and acylcarnitines were reported to be associated with IR as biomarkers most frequently. Additionally, BCAAs and tyrosine seemed to be relevant to future metabolic risk in the long-term follow-up cohorts, emphasizing the importance of early diagnosis and prevention strategy. Because of limited scale and design heterogeneity of existing studies, future studies might focus on validating above findings in more large-scale and longitudinal studies with elaborate design.

  11. Biochemical assessments of thyroid profile, serum 25-hydroxycholecalciferol and cluster of differentiation 5 expression levels among children with autism

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    Desoky T

    2017-09-01

    Full Text Available Tarek Desoky,1 Mohammed H Hassan,2 Hanan M Fayed,3 Hala M Sakhr4 1Department of Neuropsychiatry, 2Department of Medical Biochemistry and Molecular Biology, 3Department of Clinical and Chemical Pathology, 4Department of Pediatrics, Qena Faculty of Medicine, Qena University Hospitals, South Valley University, Qena, Egypt Background: The exact pathogenesis of autism is still unknown. Both thyroid hormones and 25(OHD are important for brain development, in addition to CD5; all have immunomodulatory actions by which their dysregulation may have a potential role in autism pathogenesis.Objectives: The objectives of this study were to assess the thyroid profile, serum 25(OHD levels and CD5 expression levels among autistic patients and to find out the correlations between the measured biomarkers with each other on one side and with the disease severity on the other side.Patients and methods: This cross-sectional case–control study has been conducted on 60 children with autism and 40 controls, recruited from Qena Governorate, Upper Egypt. Childhood Autism Rating Scale (CARS score was used to assess the included patients. Biochemical assays of thyroid function in the form of free triiodothyronine (FT3, free tetraiodothyronine (FT4, thyroid-stimulating hormone (TSH and 25(OHD were done using commercially available enzyme-linked immunosorbent assay (ELISA kits, while CD5 expression levels were measured using flow cytometry (FCM analysis for all the included patients and controls.Results: The overall measurement results show significant higher mean serum TSH levels, mean CD5 expression levels with significant lower mean serum 25(OHD levels among autistic children when compared with the control group (p<0.05 for all. Significant negative correlations between CD5 with FT3, FT4 and 25(OHD were observed. CARS score showed significant negative correlations with both FT3 and 25(OHD, while it was positively correlated with CD5 in a significant manner (p<0.05 for

  12. Serum Lipid Profiles, Lipid Ratios and Chronic Kidney Disease in a Chinese Population

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    Liying Zhang

    2014-07-01

    Full Text Available Aim: To examine the association of serum lipids, lipid ratios with Chronic Kidney Disease (CKD in a Chinese population. Methods: Data were drawn from a cross-sectional survey in China. CKD was defined as estimated glomerular filtration rate (eGFR < 60 mL/min/1.73m2 or albuminuria-to-creatinine ratio (ACR > 30 mg/g. Multivariable logistic regressions and multivariate regression models were used. Serum lipids and lipid ratios included total cholesterol (TC, triglyceride (TG, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, TG/HDL-C ratio, TC/HDL-C ratio and LDL-C/HDL-C ratio. Results: In men, only logarithm-transformed (log TG was associated with CKD. The odds ratio (every SD increment was 1.39 (95% CI 1.03–1.87, P = 0.03. In women, none of the serum lipids and lipid ratios was associated with CKD. Using multivariate regression models, it was shown that log TG and log TG/HDL-C were negatively correlated with eGFR (P < 0.05 in men and LDL-C and log LDL-C/HDL-C ratio were correlated with ACR in men. In female subjects, serum TC, log TG, log TG/HDL-C and log TC/HDL-C were negatively correlated with eGFR (P < 0.05. All of serum lipid profiles and lipid related ratio were not correlated with ACR in women. Conclusion: Serum TG is the only suitable predictor for CKD in men. However, in women, none of serum lipids and lipid ratio can be used as a predictor for CKD. Log TG and log TG/HDL-C are negatively correlated with eGFR in both genders.

  13. Serum PCB levels and congener profiles among teachers in PCB-containing schools: a pilot study

    Science.gov (United States)

    2011-01-01

    Background PCB contamination in the built environment may result from the release of PCBs from building materials. The significance of this contamination as a pathway of human exposure is not well-characterized, however. This research compared the serum PCB concentrations, and congener profiles between 18 teachers in PCB-containing schools and referent populations. Methods Blood samples from 18 teachers in PCB-containing schools were analyzed for 57 PCB congeners. Serum PCB concentrations and congener patterns were compared between the teachers, to the 2003-4 NHANES (National Health and Nutrition Examination Survey) data, and to data from 358 Greater Boston area men. Results Teachers at one school had higher levels of lighter (PCB 6-74) congeners compared to teachers from other schools. PCB congener 47 contributed substantially to these elevated levels. Older teachers (ages 50-64) from all schools had higher total (sum of 33 congeners) serum PCB concentrations than age-comparable NHANES reference values. Comparing the teachers to the referent population of men from the Greater Boston area (all under age 51), no difference in total serum PCB levels was observed between the referents and teachers up to 50 years age. However, the teachers had significantly elevated serum concentrations of lighter congeners (PCB 6-74). This difference was confirmed by comparing the congener-specific ratios between groups, and principal component analysis showed that the relative contribution of lighter congeners differed between the teachers and the referents. Conclusions These findings suggest that the teachers in the PCB-containing buildings had higher serum levels of lighter PCB congeners (PCB 6-74) than the referent populations. Examination of the patterns, as well as concentrations of individual PCB congeners in serum is essential to investigating the contributions from potential environmental sources of PCB exposure. PMID:21668970

  14. Ubiquitin Carboxy-Terminal Hydrolase L1 as a serum neurotrauma biomarker for exposure to occupational low-level blast

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    Walter eCarr

    2015-03-01

    Full Text Available Repeated exposure to low-level blast is a characteristic of a few select occupations and there is concern that such occupational exposures present risk for traumatic brain injury. These occupations include specialized military and law enforcement units that employ controlled detonation of explosive charges for the purpose of tactical entry into secured structures. The concern for negative effects from blast exposure is based on rates of operator self-reported headache, sleep disturbance, working memory impairment, and other concussion-like symptoms. A challenge in research on this topic has been the need for improved assessment tools to empirically evaluate the risk associated with repeated exposure to blast overpressure levels commonly considered to be too low in magnitude to cause acute injury. Evaluation of serum-based neurotrauma biomarkers provides an objective measure that is logistically feasible for use in field training environments. Among candidate biomarkers, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1 has some empirical support and was evaluated in this study.We used daily blood draws to examine acute change in UCH-L1 among 108 healthy military personnel who were exposed to repeated low-level blast across a 2-week period. These research volunteers also wore pressure sensors to record blast exposures, wrist actigraphs to monitor sleep patterns, and completed daily behavioral assessments of symptomology, postural stability, and neurocognitive function. UCH-L1 levels were elevated as a function of participating in the 2-week training with explosives, but the correlation of UCH-L1 elevation and blast magnitude was weak and inconsistent. Also, UCH-L1 elevations did not correlate with deficits in behavioral measures. These results provide some support for including UCH-L1 as a measure of central nervous system effects from exposure to low-level blast. However, the weak relation observed suggests that additional indicators of blast

  15. Can we use serum copeptin levels as a biomarker in obstructive sleep apnea syndrome?

    Science.gov (United States)

    Selcuk, Omer Tarık; Eyigor, Mete; Renda, Levent; Osma, Ustun; Eyigor, Hulya; Selcuk, Nursel Turkoglu; Yılmaz, Mustafa Deniz; Demirkıran, Cansu; Unlu, Hande; Gültekin, Meral

    2015-07-01

    The aim of this study was to compare serum copeptin levels in patients with obstructive sleep apnea syndrome (OSA) and simple snorers without sleep apnea; and to investigate relationships between copeptin levels and polysomnographic parameters. Serum copeptin levels were determined using enzyme-linked immunosorbent assay in 47 patients with OSA and 12 patients without OSA (control group). Full-night polysomnography was performed in each patient. Patients with OSA were divided into three groups according to their Apnea Hypopnea Index (AHI) scores: mild OSA (5 30). A total of 59 patients were included in the study. There were 23 female (39.0%) and 36 male (61.0%) subjects. The range of ages of study subjects was between 27 and 63 (mean 44.75 ± 9.64) years. According to the AHI values, patients were classified into four groups: simple snoring (n = 13), mild OSA (n = 10), moderate OSA (n = 15), and severe OSA (n = 21). Statistically significant differences between AHI groups in terms of age, Epworth score, and neck circumference. According to multiple comparison results for age, the difference between simple snoring and moderate OSA was statistically significant. According to multiple comparison results for Epworth score, the difference between simple snoring and severe OSA was statistically significant. According to multiple comparison results for neck circumference, a similar result was found like Epworth Sleepiness Scale score. The difference between AHI groups by gender was tested by a Pearson χ(2) test and was found to be statistically significant. There was no statistically significant difference among AHI groups in terms of copeptin. There was a statistically significant correlation of copeptin with AHI during rapid eye movement (REM) sleep; however, the correlation coefficient was not sufficiently large. Increased serum copeptin concentration may reflect a response to stress in some diseases. This is well documented especially in cardiovascular diseases

  16. Genome-wide methylation profiling identifies hypermethylated biomarkers in high-grade cervical intraepithelial neoplasia.

    Science.gov (United States)

    Lendvai, Ágnes; Johannes, Frank; Grimm, Christina; Eijsink, Jasper J H; Wardenaar, René; Volders, Haukeline H; Klip, Harry G; Hollema, Harry; Jansen, Ritsert C; Schuuring, Ed; Wisman, G Bea A; van der Zee, Ate G J

    2012-11-01

    Epigenetic modifications, such as aberrant DNA promoter methylation, are frequently observed in cervical cancer. Identification of hypermethylated regions allowing discrimination between normal cervical epithelium and high-grade cervical intraepithelial neoplasia (CIN2/3), or worse, may improve current cervical cancer population-based screening programs. In this study, the DNA methylome of high-grade CIN lesions was studied using genome-wide DNA methylation screening to identify potential biomarkers for early diagnosis of cervical neoplasia. Methylated DNA Immunoprecipitation (MeDIP) combined with DNA microarray was used to compare DNA methylation profiles of epithelial cells derived from high-grade CIN lesions with normal cervical epithelium. Hypermethylated differentially methylated regions (DMRs) were identified. Validation of nine selected DMRs using BSP and MSP in cervical tissue revealed methylation in 63.2-94.7% high-grade CIN and in 59.3-100% cervical carcinomas. QMSP for the two most significant high-grade CIN-specific methylation markers was conducted exploring test performance in a large series of cervical scrapings. Frequency and relative level of methylation were significantly different between normal and cancer samples. Clinical validation of both markers in cervical scrapings from patients with an abnormal cervical smear confirmed that frequency and relative level of methylation were related with increasing severity of the underlying CIN lesion and that ROC analysis was discriminative. These markers represent the COL25A1 and KATNAL2 and their observed increased methylation upon progression could intimate the regulatory role in carcinogenesis. In conclusion, our newly identified hypermethylated DMRs represent specific DNA methylation patterns in high-grade CIN lesions and are candidate biomarkers for early detection.

  17. miRNA profiling of circulating EpCAM(+) extracellular vesicles: promising biomarkers of colorectal cancer.

    Science.gov (United States)

    Ostenfeld, Marie Stampe; Jensen, Steffen Grann; Jeppesen, Dennis Kjølhede; Christensen, Lise-Lotte; Thorsen, Stine Buch; Stenvang, Jan; Hvam, Michael Lykke; Thomsen, Anni; Mouritzen, Peter; Rasmussen, Mads Heilskov; Nielsen, Hans Jørgen; Ørntoft, Torben Falck; Andersen, Claus Lindbjerg

    2016-01-01

    Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. These contain biomolecules, including proteins and microRNAs (miRNAs). Both circulating EVs and miRNAs have received much attention as biomarker candidates for non-invasive diagnostics. Here we describe a sensitive analytical method for isolation and subsequent miRNA profiling of epithelial-derived EVs from blood samples of patients with colorectal cancer (CRC). The epithelial-derived EVs were isolated by immunoaffinity-capture using the epithelial cell adhesion molecule (EpCAM) as marker. This approach mitigates some of the specificity issues observed in earlier studies of circulating miRNAs, in particular the negative influence of miRNAs released by erythrocytes, platelets and non-epithelial cells. By applying this method to 2 small-scale patient cohorts, we showed that blood plasma isolated from CRC patients prior to surgery contained elevated levels of 13 EpCAM(+)-EV miRNAs compared with healthy individuals. Upon surgical tumour removal, the plasma levels of 8 of these were reduced (miR-16-5p, miR-23a-3p, miR-23b-3p, miR-27a-3p, miR-27b-3p, miR-30b-5p, miR-30c-5p and miR-222-3p). These findings indicate that the miRNAs are of tumour origin and may have potential as non-invasive biomarkers for detection of CRC. This work describes a non-invasive blood-based method for sensitive detection of cancer with potential for clinical use in relation to diagnosis and screening. We used the method to study CRC; however, it is not restricted to this disease. It may in principle be used to study any cancer that release epithelial-derived EVs into circulation.

  18. Analysis of Isocitrate Dehydrogenase -2 (IDH-2) Activity in Human Serum as a Biomarker in Chemotherapy Patients of Breast Carcinoma: A Case-Control Study.

    Science.gov (United States)

    Gavel, Roshni; Mishra, S P; Khanna, Seema; Khanna, Rahul; Shah, Agni Gautam

    2017-05-01

    Breast cancer represents a major public health problem in women worldwide. For many cancers, serum tumour markers play an important role in patient treatment and monitoring. Isocitrate dehydrogenase enzyme is also used as a biomarker for various types of cancer. The purpose of this study was to determine serum Isocitrate dehydrogenase-2 (IDH-2) enzyme activity in breast cancer patients (pre and post chemotherapy) and also correlate the changes in enzyme activity with stages of cancer and control groups. In this case-control study, histologically confirmed 40 female patients aged 28-80 years who fulfilled the criteria for diagnosis of invasive breast cancer were selected in our study groups from surgery outpatient department of SS Hospital, BHU, Varanasi, India, and 40 healthy age matched females were selected between October 2013 to July 2015. The estimation of serum IDH-2 enzyme activity in before and after two cycles of neoadjuvant chemotherapy patients was performed by spectrophotometry assay. The mean serum IDH-2 activity in cases (Mean±SD) was significantly more than control group (pIDH-2 activity in cases was significantly decrease after neo-adjuvant chemotherapy (p=0.019). In stage II pre chemotherapy patients serum IDH-2 activity was higher than post chemotherapy (pIDH-2 activity was not significant (p-value>0.05). The serum IDH-2 can be a potential biomarker in breast carcinoma and can be used for prognosis and monitoring the chemotherapy response of the patients.

  19. Identification of peptide regions of SERPINA1 and ENOSF1 and their protein expression as potential serum biomarkers for gastric cancer.

    Science.gov (United States)

    Yang, Juan; Xiong, Xiaofan; Wang, Xiaofei; Guo, Bo; He, Kang; Huang, Chen

    2015-07-01

    This study aimed to detect potential serum biomarkers for gastric cancer. In the present study, we used magnetic bead-based purification and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry to detect potential serum markers in 70 gastric cancer (GC) patients compared with 72 healthy controls. On average, up to 81 peaks, of which 11 were significantly different m/z peaks (fold change >1.5; P SERPINA1 and ENOSF1. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze 210 additional serum samples obtained from 36 healthy volunteers, 36 GC patients, 30 GU patients, 36 nonsmall-cell lung cancer (NSCLC) patients, 36 clear-cell renal cell carcinoma (CCRCC) patients, and 36 pancreatic cancer patients to verify the expression of SERPINA1 and ENOSF1 in GC sera. The suitability of the present method for gastric serum proteomic analysis was demonstrated and led to the identification of two peptide regions and their corresponding proteins as potential serum biomarkers for the serum detection of GC.

  20. Longitudinal Bank for Serum, Plasma and DNA for Detection of Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Ward, David C

    2009-01-31

    With the support of this DOE appropriation, NVCI has established a biorepository for serum, plasma, DNA and urine specimens. Over 2,500 patients have been consented which is over 90% of all new patients seen at NVCI. The specimens have been coded, centrifuged, aliquoted and frozen at -80°C in a rapid manner so that they are all processed in less than 1 hour from the acquisition. There are over 28,000 aliquoted, coded tubes in our inventory. Specimens from 200 control volunteer subjects without any history of cancer also have been banked. The patient specimens are encoded and the demographics and therapeutic treatments are linked to the Oncore software. This computer program catalogues the specimens and provides a rapid conduit between the biorepository and the NVCI electronic medical record.

  1. A pilot study to investigate the potential of mass spectrometry profiling in the discovery of novel serum markers in chronic renal disease.

    Science.gov (United States)

    Thompson, Douglas; Develter, Willem; Cairns, David A; Barrett, Jennifer H; Perkins, David A; Stanley, Anthea J; Mooney, Andrew; Selby, Peter J; Banks, Rosamonde E

    2011-10-01

    There has been significant criticism of how technologies such as SELDI have been used in biomarker discovery and how the data have been analysed. We initiated a proof-of-principle pilot study using SELDI with stringent pre-analytic and analytical procedures with robust statistical analysis, to determine whether, under such conditions, using different degrees of renal dysfunction as a model, useful data could be obtained. SELDI-TOF-MS profiling with stringent quality control measures was used to examine the proteomic profile of serum from healthy controls (n=30), patients with end-stage renal failure being treated by dialysis (n=30) and renal transplant patients (n=50) with varying degrees of graft stability. Principal component analysis of the data suggests that the continuum from normality to end-stage renal failure through 'stable' and 'unstable' transplant may be detected by SELDI profiling. Serum β2 microglobulin was identified as a major component and this was validated using immunonephelometry. This pilot study suggests that stringently controlled SELDI analysis is able to detect proteins which may be useful in the stratification of patients post-renal transplant. Further studies using a larger cohort of patients with chronic allograft dysfunction, defined by protocol biopsies, are indicated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Lipid profile and serum characteristics of the blind subterranean mole rat, Spalax.

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    Nicola J Nasser

    Full Text Available BACKGROUND: Spalax (blind subterranean mole rat, is a mammal adapted to live in fluctuating oxygen levels, and can survive severe hypoxia and hypercapnia. The adaptive evolution of Spalax to underground life resulted in structural and molecular-genetic differences comparing to above-ground mammals. These differences include higher myocardial maximal oxygen consumption, increased lung diffusion capacity, increased blood vessels density, and unique expression patterns of cancer and angiogenesis related genes such as heparanase, vascular endothelial growth factor, and P53. METHODOLOGY/PRINCIPAL FINDINGS: Here we elucidate the main characteristics of Spalax lipid profile, as well as its main antioxidant and serum parameters. Compared to human, Spalax possesses lower total-cholesterol, low density lipoproteins (LDL and triglycerides levels, and higher levels of high density lipoproteins (HDL. Apolipoprotein A-I and apolipoprotein B-100 were significantly lower in Spalax compared to human. Paraoxonase (PON 1 arylesterase activity, was higher in Spalax compared to both human and mouse serum levels. Analysis of serum chemistry of Spalax revealed special features in this mammal. CONCLUSIONS/SIGNIFICANCE: Spalax possesses a unique lipid profile with high HDL and low LDL lipoproteins. The antioxidant serum content in the mole rat is higher than that of human and mouse. Serum C reactive protein (CRP levels are significantly lower in Spalax compared to that of human or mouse, reflecting low levels of inflammation. These differences between Spalax, human and mouse are due to several factors including the intensive activity life-style that Spalax pursue underground, dietary components, and evolutionary genetic adaptations. Unfolding the genetic basis of these differences will probably result in unique treatments for a variety of human diseases such as dyslipedemias, inflammation and cancer.

  3. Temperament Type Specific Metabolite Profiles of the Prefrontal Cortex and Serum in Cattle

    Science.gov (United States)

    Brand, Bodo; Hadlich, Frieder; Brandt, Bettina; Schauer, Nicolas; Graunke, Katharina L.; Langbein, Jan; Repsilber, Dirk; Ponsuksili, Siriluk; Schwerin, Manfred

    2015-01-01

    In the past decade the number of studies investigating temperament in farm animals has increased greatly because temperament has been shown not only to affect handling but also reproduction, health and economically important production traits. However, molecular pathways underlying temperament and molecular pathways linking temperament to production traits, health and reproduction have yet to be studied in full detail. Here we report the results of metabolite profiling of the prefrontal cortex and serum of cattle with distinct temperament types that were performed to further explore their molecular divergence in the response to the slaughter procedure and to identify new targets for further research of cattle temperament. By performing an untargeted comprehensive metabolite profiling, 627 and 1097 metabolite features comprising 235 and 328 metabolites could be detected in the prefrontal cortex and serum, respectively. In total, 54 prefrontal cortex and 51 serum metabolite features were indicated to have a high relevance in the classification of temperament types by a sparse partial least square discriminant analysis. A clear discrimination between fearful/neophobic-alert, interested-stressed, subdued/uninterested-calm and outgoing/neophilic-alert temperament types could be observed based on the abundance of the identified relevant prefrontal cortex and serum metabolites. Metabolites with high relevance in the classification of temperament types revealed that the main differences between temperament types in the response to the slaughter procedure were related to the abundance of glycerophospholipids, fatty acyls and sterol lipids. Differences in the abundance of metabolites related to C21 steroid metabolism and oxidative stress indicated that the differences in the metabolite profiles of the four extreme temperament types could be the result of a temperament type specific regulation of molecular pathways that are known to be involved in the stress and fear response

  4. Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    Science.gov (United States)

    Background: Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. Objective: We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help ...

  5. Proteome Profiling of Diabetic Mellitus Patient Urine for Discovery of Biomarkers by Comprehensive MS-Based Proteomics

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    Yoshitoshi Hirao

    2018-02-01

    Full Text Available Diabetic mellitus (DM is a disease that affects glucose homeostasis and causes complications, such as diabetic nephropathy (DN. For early diagnosis of DN, microalbuminuria is currently one of the most frequently used biomarkers. However, more early diagnostic biomarkers are desired in addition to microalbuminuria. In this study, we performed comprehensive proteomics analysis of urine proteomes of diabetic mellitus patients without microalbuminuria and healthy volunteers to compare the protein profiles by mass spectrometry. With high confidence criteria, 942 proteins in healthy volunteer urine and 645 proteins in the DM patient urine were identified with label-free semi-quantitation, respectively. Gene ontology and pathway analysis were performed with the proteins, which were up- or down-regulated in the DM patient urine to elucidate significant changes in pathways. The discovery of a useful biomarker for early DN discovery is expected.

  6. Serum C-Reactive Protein Level as a Biomarker for Differentiation of Ischemic from Hemorrhagic Stroke

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    Seyed Ali Roudbary

    2011-03-01

    Full Text Available Cerebrovascular accidents rank first in the frequency and importance among all neurological disease. Although a number of studies had shown increased level of the high sensitive C-reactive protein (hs-CRP in patients with ischemic stroke, the association of increased hs-CRP with various type of stroke especially the assessment hs-CRP level in ischemic and hemorrhagic stroke have not been investigated. In the present study, we assessed the concentration of hs-CRP in patients with documented ischemic and hemorrhagic stroke in the first 24 hours of the onset of symptoms. Thirty-two patients with Ischemic and hemorrhagic stroke were evaluated at neurology department of Poursina Hospital. The presence of baseline vascular risk factors, including hypertension, diabetes mellitus, hypercholesterolemia, obesity, and smoking, was determined. The blood samples were then collected and routine hematology and biochemistry tests were done. hs-CRP levels were determined using a highly sensitive immunonephelometric method. In this cross sectional study, the age of patient varied from 45-85 years (Mean 70.9  9.4. Serum level of hs-CRP in Ischemic patients were 18.92  11.28 and in hemorrhagic group was 2.65  1.7. This relationship was statistically significant (P<0.0001. It might be concluded that hs-CRP might be considered as a usefully adjunct method for the initial diagnosis of the type of stroke.

  7. Serum properdin consumption as a biomarker of C5 convertase dysregulation in C3 glomerulopathy.

    Science.gov (United States)

    Corvillo, F; Bravo García-Morato, M; Nozal, P; Garrido, S; Tortajada, A; Rodríguez de Córdoba, S; López-Trascasa, M

    2016-04-01

    Properdin (P) stabilizes the alternative pathway (AP) convertases, being the only known positive regulator of the complement system. In addition, P is a pattern recognition molecule able to initiate directly the AP on non-self surfaces. Although P deficiencies have long been known to be associated with Neisseria infections and P is often found deposited at sites of AP activation and tissue injury, the potential role of P in the pathogenesis of complement dysregulation-associated disorders has not been studied extensively. Serum P levels were measured in 49 patients with histological and clinical evidence of C3 glomerulopathy (C3G). Patients were divided into two groups according to the presence or absence of C3 nephritic factor (C3NeF), an autoantibody that stabilizes the AP C3 convertase. The presence of this autoantibody results in a significant reduction in circulating C3 (P C5 levels (P C5 (P C5 (r = 0·806, P C5 convertase dysregulation. © 2016 British Society for Immunology.

  8. Serum homocysteine and lipid profile levels in patients with type2 diabetes mellitus

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    Balu Mahendran K, Santha K, Santhosh kumar N, Gnana Desigan E S

    2013-02-01

    Full Text Available Serum total homocysteine (tHcy concentration is associated with increased risk factor for coronary heart diseases (CHD. The relation between type2 diabetes mellitus compared to the non diabetics is not clear. The current study represents an association between tHcy and cardiovascular disease is stronger in diabetics than in non-diabetic subjects. Materials & methods: Thirty type2 diabetic patients of both sexes with age group between 35-50 years selected as a study group. Thirty healthy, ages, both sexes’ subjects were selected as controls. Patients on insulin, Smokers, Alcoholics, Tobacco chewers, Hypertension, and other systemic illness were excluded from this study. Glucose, Lipid profile parameters analysed by fully automated analyzer. Total homocysteine is analyzed by enzyme immunoassay method. Results: The mean level of Glucose, serum Cholesterol, Triglycerides, LDL, and total Hcy levels are increased in type2 diabetic patients compared to the control group. The HDL level is significantly decreased in type2 diabetic patients compared to control group. Conclusion: The Serum total Hcy levels are associated with lipid profile in type2 diabetic patients. An elevated level of total Hcy leads coronary heart diseases.

  9. The effect of fat intake and antihypertensive drug therapy on serum lipid profile: a cross-sectional survey of serum lipids in male and female hypertensives.

    Science.gov (United States)

    Sharma, Rakesh; Raghuram, T C; Rao, U Brahmoji; Moffatt, Robert J; Krishnaswamy, Kamla

    2010-10-01

    The present study aimed to investigate the effect of betablocker with diuretics therapy on serum cholesterol and high density lipoprotein (HDL-C) lipids in cross-sectional data (age, sex, weight, and body mass index (BMI), smoking/alcoholic consumption) and supplemented vegetarian low-fat diet with daily low fat energy intake, salt intake, duration of drug therapy, and serum protein as effective measures of lowering blood pressure among hypertensives in both males and females. Hypertensive patients on betablocker and/or thiazide therapy were compared in cross-section study with their age, blood pressure, fat intake, serum lipid profile, BMI, and serum albumin in males and females. Dietary fat intake and serum lipid profile were income related. Betablocker and diuretics therapy in combination with dietary fat intervention was beneficial for prolonged dyslipidemia control. Serum cholesterol level was main contributing factor dependent on BMI, duration of drug, and socio-economic factors. Fat intake contributed in hypertension and serum cholesterol levels. A cross-sectional data analysis showed beneficial effects of "low fat-salt-smoking-alcohol consumption and combined polyunsaturated fatty acid with antihypertensive therapy approach" to keep normal dyslipidemia and hypertension. Low fat intake, low salt, smoking, alcohol consumption, and combination of dietary oil supplements with lipid betablockers and diuretic modulators were associated with low hypertension and controlled dyslipidemia in Asian sedentary population.

  10. DNA methylation profiles of the brain-derived neurotrophic factor (BDNF gene as a potent diagnostic biomarker in major depression.

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    Manabu Fuchikami

    Full Text Available Major depression, because of its recurring and life-threatening nature, is one of the top 10 diseases for global disease burden. Major depression is still diagnosed on the basis of clinical symptoms in patients. The search for specific biological markers is of great importance to advance the method of diagnosis for depression. We examined the methylation profile of 2 CpG islands (I and IV at the promoters of the brain-derived neurotrophic factor (BDNF gene, which is well known to be involved in the pathophysiology of depression. We analyzed genomic DNA from peripheral blood of 20 Japanese patients with major depression and 18 healthy controls to identify an appropriate epigenetic biomarker to aid in the establishment of an objective system for the diagnosis of depression. Methylation rates at each CpG unit was measured using a MassArray® system (SEQUENOM, and 2-dimensional hierarchical clustering analyses were undertaken to determine the validity of these methylation profiles as a diagnostic biomarker. Analyses of the dendrogram from methylation profiles of CpG I, but not IV, demonstrated that classification of healthy controls and patients at the first branch completely matched the clinical diagnosis. Despite the small number of subjects, our results indicate that classification based on the DNA methylation profiles of CpG I of the BDNF gene may be a valuable diagnostic biomarker for major depression.

  11. Metal-linked Immunosorbent Assay (MeLISA): the Enzyme-Free Alternative to ELISA for Biomarker Detection in Serum.

    Science.gov (United States)

    Yu, Ru-Jia; Ma, Wei; Liu, Xiao-Yuan; Jin, Hong-Ying; Han, Huan-Xing; Wang, Hong-Yang; Tian, He; Long, Yi-Tao

    2016-01-01

    Determination of disease biomarkers in clinical samples is of crucial significance for disease monitoring and public health. The dominating format is enzyme-linked immunosorbent assay (ELISA), which subtly exploits both the antigen-antibody reaction and biocatalytic property of enzymes. Although enzymes play an important role in this platform, they generally suffer from inferior stability and less tolerant of temperature, pH condition compared with general chemical product. Here, we demonstrate a metal-linked immunosorbent assay (MeLISA) based on a robust signal amplification mechanism that faithfully replaces the essential element of the enzyme. As an enzyme-free alternative to ELISA, this methodology works by the detection of α-fetoprotein (AFP), prostatic specific antigen (PSA) and C-reactive protein (CRP) at concentrations of 0.1 ng mL(-1), 0.1 ng mL(-1) and 1 ng mL(-1) respectively. It exhibits approximately two magnitudes higher sensitivity and is 4 times faster for chromogenic reaction than ELISA. The detection of AFP and PSA was further confirmed by over a hundred serum samples from hepatocellular carcinoma (HCC) and prostate cancer patients respectively.

  12. Serum dickkopf-1 as a biomarker in screening gastrointestinal cancers: a systematic review and meta-analysis

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    Liang B

    2015-10-01

    available evidence suggests that serum DKK1 is a potential biomarker with high SEN and SPE for screening GI cancers. To better elucidate the usefulness of serum DKK1, further studies are needed. Keywords: gastrointestinal cancer, dickkopf-1, cancer screening, accuracy

  13. Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage.

    Science.gov (United States)

    Cakir, Murteza; Calikoglu, Cagatay; Yılmaz, Atilla; Akpinar, Erol; Bayraktutan, Zafer; Topcu, Atilla

    2017-02-01

    Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± 1.89 pg/ml in the survival group. Furthermore, it was 10.22 ± 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.01 for all). The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management.

  14. CSF biomarkers and neuropsychological profiles in patients with cerebral small-vessel disease.

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    Peter Hermann

    Full Text Available Despite existing criteria, differential diagnosis of Vascular Dementia (VD and Alzheimer's disease (AD remains difficult. The aim of this study is to figure out cognitive and biomarker profiles that may help to distinguish between VD, AD and AD + Cerebral Small Vessel Disease (CSVD. We examined a cohort of patients with CSVD (n = 92. After stratification of cognitive impaired patients (n = 59 using the standard CSF beta-amyloid 42/40 ratio cut-off point of 0.975, we obtained two groups which differed with respect to several features: 32 patients with normal beta-amyloid 42/40 ratio (>0.975 showed markedly impaired blood-brain-barrier function as indicated by an elevated albumin ratio (median 8.35. They also differed in cognitive profiles when compared to 27 patients with AD typical beta-amyloid ratio and normal albumin ratio. We also enrolled an additional group of patients with AD (no significant CSVD on MRI, n = 27 which showed no impairment of the blood-brain-barrier. We showed a negative correlation between the albumin ratio and executive cognitive function (p = 0.016 and a negative correlation between memory function and typical AD markers like Tau (p = 0.004 and p181-Tau (p = 0.023 in our cohort. We suppose that the group of patients with normal beta-amyloid ratio represents VD while patients in the other groups represent AD+CSVD and pure AD. Our results support the idea that a dysfunction of the blood-brain-barrier might be contributing factor in the development of cognitive decline in CSVD as it seems to be of more importance than the severity of white matter lesions.

  15. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    Science.gov (United States)

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  16. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

    Science.gov (United States)

    Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

    2014-08-01

    There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  17. A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight

    Directory of Open Access Journals (Sweden)

    Braun Joe M

    2010-08-01

    Full Text Available Abstract Background The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure. Methods We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression. Results We detected nicotine (80%, cotinine (69%, and trans-3'-hydroxycotinine (57% in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight. Conclusions Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.

  18. Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings.

    Science.gov (United States)

    Troiano, Giuseppe; Boldrup, Linda; Ardito, Fatima; Gu, Xaolian; Lo Muzio, Lorenzo; Nylander, Karin

    2016-12-01

    The purpose of this systematic review was to summarize current findings on the use of circulating miRNAs from blood, serum and plasma as cancer biomarkers in patients with oral squamous cell carcinoma. Studies were gathered after searching four different electronic databases: PUBMED, SCOPUS, Cochrane Library and Web of Science. Additional search was carried out through cross check on bibliography of selected articles. After the selection process made by two of the authors, 16 articles met the inclusion criteria and were included in the review. Results showed that circulating miRNAs from blood, serum or plasma represent promising candidates as cancer biomarkers in patients suffering from oral cancer. The possibility to predict recurrences and metastases through follow-up quantification of candidate miRNAs represents another potential feature to be addressed in future studies. However, methodological standardization and uniform sampling is needed to increase the power and accuracy of results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Serum lipid profiles are associated with disability and MRI outcomes in multiple sclerosis

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    Weinstock-Guttman Bianca

    2011-10-01

    Full Text Available Abstract Background The breakdown of the blood-brain-barrier vascular endothelium is critical for entry of immune cells into the MS brain. Vascular co-morbidities are associated with increased risk of progression. Dyslipidemia, elevated LDL and reduced HDL may increase progression by activating inflammatory processes at the vascular endothelium. Objective To assess the associations of serum lipid profile variables (triglycerides, high and low density lipoproteins (HDL, LDL and total cholesterol with disability and MRI measures in multiple sclerosis (MS. Methods This study included 492 MS patients (age: 47.1 ± 10.8 years; disease duration: 12.8 ± 10.1 years with baseline and follow-up Expanded Disability Status Score (EDSS assessments after a mean period of 2.2 ± 1.0 years. The associations of baseline lipid profile variables with disability changes were assessed. Quantitative MRI findings at baseline were available for 210 patients. Results EDSS worsening was associated with higher baseline LDL (p = 0.006 and total cholesterol (p = 0.001, 0.008 levels, with trends for higher triglyceride (p = 0.025; HDL was not associated. A similar pattern was found for MSSS worsening. Higher HDL levels (p p = 0.033. Conclusions Serum lipid profile has modest effects on disease progression in MS. Worsening disability is associated with higher levels of LDL, total cholesterol and triglycerides. Higher HDL is associated with lower levels of acute inflammatory activity.

  20. Consumption of pasteurized human lysozyme transgenic goats' milk alters serum metabolite profile in young pigs.

    Science.gov (United States)

    Brundige, Dottie R; Maga, Elizabeth A; Klasing, Kirk C; Murray, James D

    2010-08-01

    Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats' milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats' milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health.

  1. Investigation the effect of Commiphora mukul on blood glucose and Serum lipid profile in diabetic rats

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    leila Shirazi

    2015-01-01

    Full Text Available Background & aim: The decrease of serum glucose level and lipids in diabetic patients is clinically significant. The purpose of this study was to determine the effect of Commiphora mukul extract on blood sugar and lipid profile in diabetic rats. Methods: In the present experimental study, thirty-two male Wistar rats were randomly divided into four groups: control, control treated with the extract, diabetic and diabetic treated with the extract. Diabetes was induced by intraperitoneal injection of Streptozotocin. In an eight week period, the control group of normal saline and the control group and diabetic recipient extract of CM oleo gum blue resin was given by gavage. Treatment resumed eight weeks with onset of hyperglycemia. The control and diabetic control groups received normal saline orally. Extract treated control and extract treated diabetic groups received extract of Commiphora mukul gum (300 mg/kg P.O. daily by gavage. At the end of this period, blood samples were collected from each rat and biochemical tests for investigation of glucose level and lipid profile was performed. One- way analysis of variance (ANOVA statistical test and Post-hoc test Tukey’s were used for data analysis Results: The study indicated that diabetes increases the serum levels of glucose, cholesterol, triglycerides, LDL and HDL. Administration of Commiphora mukul gum extract in diabetic groups significantly decreased the serum level of glucose, cholesterol(p<0.01 and triglyceride and LDL(p<0.001 and increased HDL(p<0.01. Conclusion: Commiphora mukul gum extract may well improve undesirable effects of diabetes on serum level of glucose, cholesterol, triglyceride, LDL and HDL.

  2. Serum lipidomics meets cardiac magnetic resonance imaging: profiling of subjects at risk of dilated cardiomyopathy.

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    Marko Sysi-Aho

    Full Text Available Dilated cardiomyopathy (DCM, characterized by left ventricular dilatation and systolic dysfunction, constitutes a significant cause for heart failure, sudden cardiac death or need for heart transplantation. Lamin A/C gene (LMNA on chromosome 1p12 is the most significant disease gene causing DCM and has been reported to cause 7-9% of DCM leading to cardiac transplantation. We have previously performed cardiac magnetic resonance imaging (MRI to LMNA carriers to describe the early phenotype. Clinically, early recognition of subjects at risk of developing DCM would be important but is often difficult. Thus we have earlier used the MRI findings of these LMNA carriers for creating a model by which LMNA carriers could be identified from the controls at an asymptomatic stage. Some LMNA mutations may cause lipodystrophy. To characterize possible effects of LMNA mutations on lipid profile, we set out to apply global serum lipidomics using Ultra Performance Liquid Chromatography coupled to mass spectrometry in the same LMNA carriers, DCM patients without LMNA mutation and controls. All DCM patients, with or without LMNA mutation, differed from controls in regard to distinct serum lipidomic profile dominated by diminished odd-chain triglycerides and lipid ratios related to desaturation. Furthermore, we introduce a novel approach to identify associations between the molecular lipids from serum and the MR images from the LMNA carriers. The association analysis using dependency network and regression approaches also helped us to obtain novel insights into how the affected lipids might relate to cardiac shape and volume changes. Our study provides a framework for linking serum derived molecular markers not only with clinical endpoints, but also with the more subtle intermediate phenotypes, as derived from medical imaging, of potential pathophysiological relevance.

  3. Moving toward endotypes in atopic dermatitis: Identification of patient clusters based on serum biomarker analysis.

    Science.gov (United States)

    Thijs, Judith L; Strickland, Ian; Bruijnzeel-Koomen, Carla A F M; Nierkens, Stefan; Giovannone, Barbara; Csomor, Eszter; Sellman, Bret R; Mustelin, Tomas; Sleeman, Matthew A; de Bruin-Weller, Marjolein S; Herath, Athula; Drylewicz, Julia; May, Richard D; Hijnen, DirkJan

    2017-09-01

    Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease with a diverse clinical presentation. However, it is unclear whether this diversity exists at a biological level. We sought to test the hypothesis that AD is heterogeneous at the biological level of individual inflammatory mediators. Sera from 193 adult patients with moderate-to-severe AD (six area, six sign atopic dermatitis [SASSAD] score: geometric mean, 22.3 [95% CI, 21.3-23.3] and 39.1 [95% CI, 37.5-40.9], respectively) and 30 healthy control subjects without AD were analyzed for 147 serum mediators, total IgE levels, and 130 allergen-specific IgE levels. Population heterogeneity was assessed by using principal component analysis, followed by unsupervised k-means cluster analysis of the principal components. Patients with AD showed pronounced evidence of inflammation compared with healthy control subjects. Principal component analysis of data on sera from patients with AD revealed the presence of 4 potential clusters. Fifty-seven principal components described approximately 90% of the variance. Unsupervised k-means cluster analysis of the 57 largest principal components delivered 4 distinct clusters of patients with AD. Cluster 1 had high SASSAD scores and body surface areas with the highest levels of pulmonary and activation-regulated chemokine, tissue inhibitor of metalloproteinases 1, and soluble CD14. Cluster 2 had low SASSAD scores with the lowest levels of IFN-α, tissue inhibitor of metalloproteinases 1, and vascular endothelial growth factor. Cluster 3 had high SASSAD scores with the lowest levels of IFN-β, IL-1, and epithelial cytokines. Cluster 4 had low SASSAD scores but the highest levels of the inflammatory markers IL-1, IL-4, IL-13, and thymic stromal lymphopoietin. AD is a heterogeneous disease both clinically and biologically. Four distinct clusters of patients with AD have been identified that could represent endotypes with unique biological mechanisms. Elucidation of

  4. Serum protein profiles as potential biomarkers for infectious disease status in pigs

    NARCIS (Netherlands)

    Koene, M.G.J.; Mulder, H.A.; Stockhofe, N.; Kruijt, L.; Smits, M.A.

    2012-01-01

    Background: In veterinary medicine and animal husbandry, there is a need for tools allowing the early warning of diseases. Preferably, tests should be available that warn farmers and veterinarians during the incubation periods of disease and before the onset of clinical signs. The objective of this

  5. The future of liquid chromatography-mass spectrometry in metabolic profiling and metabolomic studies for biomarker discovery.

    Energy Technology Data Exchange (ETDEWEB)

    Metz, Thomas O.; Zhang, Qibin; Page, Jason S.; Shen, Yufeng; Callister, Stephen J.; Jacobs, Jon M.; Smith, Richard D.

    2007-06-01

    The future utility of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discover will be discussed, beginning with a brief description of the evolution of metabolomics and the utilization of the three most popular analytical platforms in such studies: NMR, GC-MS, and LC-MS. Emphasis is placed on recent developments in high-efficiency LC separations and sensitive electrospray ionization approaches and the benefits to incorporating both in LC-MS-based approaches. The advantages and disadvantages of various quantitative approaches are reviewed, followed by the current LC-MS-based tools available for candidate biomarker characterization and identification. Finally, a brief prediction on the future path of LC-MS-based methods in metabolic profiling and metabolomic studies is given.

  6. Alteration of the fecal microbiota and serum metabolite profiles in dogs with idiopathic inflammatory bowel disease.

    Science.gov (United States)

    Minamoto, Yasushi; Otoni, Cristiane C; Steelman, Samantha M; Büyükleblebici, Olga; Steiner, Jörg M; Jergens, Albert E; Suchodolski, Jan S

    2015-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common cause of chronic gastrointestinal (GI) disease in dogs. The combination of an underlying host genetic susceptibility, an intestinal dysbiosis, and dietary/environmental factors are suspected as main contributing factors in the pathogenesis of canine IBD. However, actual mechanisms of the host-microbe interactions remain elusive. The aim of this study was to compare the fecal microbiota and serum metabolite profiles between healthy dogs (n = 10) and dogs with IBD before and after 3 weeks of medical therapy (n = 12). Fecal microbiota and metabolite profiles were characterized by 454-pyrosequencing of 16 S rRNA genes and by an untargeted metabolomics approach, respectively. Significantly lower bacterial diversity and distinct microbial communities were observed in dogs with IBD compared to the healthy control dogs. While Gammaproteobacteria were overrepresented, Erysipelotrichia, Clostridia, and Bacteroidia were underrepresented in dogs with IBD. The functional gene content was predicted from the 16 S rRNA gene data using PICRUSt, and revealed overrepresented bacterial secretion system and transcription factors, and underrepresented amino acid metabolism in dogs with IBD. The serum metabolites 3-hydroxybutyrate, hexuronic acid, ribose, and gluconic acid lactone were significantly more abundant in dogs with IBD. Although a clinical improvement was observed after medical therapy in all dogs with IBD, this was not accompanied by significant changes in the fecal microbiota or in serum metabolite profiles. These results suggest the presence of oxidative stress and a functional alteration of the GI microbiota in dogs with IBD, which persisted even in the face of a clinical response to medical therapy.

  7. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance.

    Directory of Open Access Journals (Sweden)

    Nury M Steuerwald

    Full Text Available Drug-induced liver injury (DILI is the most common cause of acute liver failure in the United-States. The aim of the study was to describe serum immune profiles associated with acute DILI, to investigate whether there are profiles associated with clinical features or types of DILI and/or with prognosis, and to assess temporal changes in levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects in the Drug-Induced Liver Injury Network (DILIN and compared with 40 healthy controls. Immune analytes (14 cytokines, 7 chemokines and 6 growth factors were measured by BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing immune principles was used to select a final set of variables among 27 immune analytes and several additional clinical lab values for prediction of early death (within 6 months of DILI onset. Nineteen of the 27 immune analytes were differentially expressed among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune responses, especially innate and adaptive cellular (mostly TH17 immunity were evident. Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES and serum albumin are predictive of early death [PPV = 88% (95% CI, 65%-100%, NPV = 97% (95% CI, 93%-100%, accuracy = 96% (95% CI, 92%-100%].Acute DILI is associated with robust and varying immune responses. High levels of expression of cytokines associated with innate immunity are associated with a poor prognosis, whereas high levels of expression of adaptive cytokines are associated with good long-term prognosis and eventual recovery. Serum immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic significance.

  8. A biomarker profile for predicting efficacy of cisplatin-vinorelbine therapy in malignant pleural mesothelioma

    DEFF Research Database (Denmark)

    Zimling, Zarah Glad; Sørensen, Jens Benn; Gerds, Thomas Alexander

    2012-01-01

    Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated with cispl......Malignant pleural mesothelioma (MPM) has a dismal prognosis. Treatment results may be improved by biomarker-directed therapy. We investigated the baseline expression and impact on outcome of predictive biomarkers ERCC1, BRCA1, and class III β-tubulin in a cohort of MPM patients treated...

  9. Circulating Biomarkers for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Aartsma-Rus, Annemieke; Spitali, Pietro

    2015-07-22

    Duchenne muscular dystrophy is the most common form of muscular dystrophy. Genetic and biochemical research over the years has characterized the cause, pathophysiology and development of the disease providing several potential therapeutic targets and/or biomarkers. High throughput - omic technologies have provided a comprehensive understanding of the changes occurring in dystrophic muscles. Murine and canine animal models have been a valuable source to profile muscles and body fluids, thus providing candidate biomarkers that can be evaluated in patients. This review will illustrate known circulating biomarkers that could track disease progression and response to therapy in patients affected by Duchenne muscular dystrophy. We present an overview of the transcriptomic, proteomic, metabolomics and lipidomic biomarkers described in literature. We show how studies in muscle tissue have led to the identification of serum and urine biomarkers and we highlight the importance of evaluating biomarkers as possible surrogate endpoints to facilitate regulatory processes for new medicinal products.

  10. Aging and sarcopenia associate with specific interactions between gut microbes, serum biomarkers and host physiology in rats.

    Science.gov (United States)

    Siddharth, Jay; Chakrabarti, Anirikh; Pannérec, Alice; Karaz, Sonia; Morin-Rivron, Delphine; Masoodi, Mojgan; Feige, Jerome N; Parkinson, Scott James

    2017-07-17

    The microbiome has been demonstrated to play an integral role in the maintenance of many aspects of health that are also associated with aging. In order to identify areas of potential exploration and intervention, we simultaneously characterized age-related alterations in gut microbiome, muscle physiology and serum proteomic and lipidomic profiles in aged rats to define an integrated signature of the aging phenotype. We demonstrate that aging skews the composition of the gut microbiome, in particular by altering the Sutterella to Barneseilla ratio, and alters the metabolic potential of intestinal bacteria. Age-related changes of the gut microbiome were associated with the physiological decline of musculoskeletal function, and with molecular markers of nutrient processing/availability, and inflammatory/immune status in aged versus adult rats. Altogether, our study highlights that aging leads to a complex interplay between the microbiome and host physiology, and provides candidate microbial species to target physical and metabolic decline during aging by modulating gut microbial ecology.

  11. Serum cytokine profiles as predictors of asthma control in adults from the EGEA study.

    Science.gov (United States)

    Akiki, Zeina; Rava, Marta; Diaz Gil, Oscar; Pin, Isabelle; le Moual, Nicole; Siroux, Valérie; Guerra, Stefano; Chamat, Soulaima; Matran, Regis; Fitó, Montserrat; Salameh, Pascale; Nadif, Rachel

    2017-04-01

    To which extent serum cytokines may predict asthma control in adults remains understudied. We investigated cross-sectional and longitudinal associations between cytokine profiles and asthma outcomes. Serum interleukin (IL)-1Ra, IL-5, IL-7, IL-8, IL-10, IL-13 and TNF-α levels were determined in 283 adults with current asthma from the 2nd survey of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2). Participants were followed-up seven years later. Asthma symptom control was assessed according to GINA 2015 guidelines. Cytokine profiles were identified by principal component (PC) analyses, and expressed as above/below the median. The first two PCs captured 82.5% of the variability. While all seven cytokines scored high on PC1, only IL-1Ra and IL-10 scored high on PC2. At EGEA2, neither PC1 nor PC2 were related to exacerbations, asthma attacks, asthma symptom control, lung function, or alle