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Sample records for serum biomarker profiling

  1. Multiplex immune serum biomarker profiling in sarcoidosis and systemic sclerosis.

    PubMed

    Beirne, P; Pantelidis, P; Charles, P; Wells, A U; Abraham, D J; Denton, C P; Welsh, K I; Shah, P L; du Bois, R M; Kelleher, P

    2009-12-01

    Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients. We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher's discriminant function analysis to establish the groups of classification mediators. There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients. These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution. PMID:19541722

  2. Analytical considerations for mass spectrometry profiling in serum biomarker discovery.

    PubMed

    Whiteley, Gordon R; Colantonio, Simona; Sacconi, Andrea; Saul, Richard G

    2009-03-01

    The potential of using mass spectrometry profiling as a diagnostic tool has been demonstrated for a wide variety of diseases. Various cancers and cancer-related diseases have been the focus of much of this work because of both the paucity of good diagnostic markers and the knowledge that early diagnosis is the most powerful weapon in treating cancer. The implementation of mass spectrometry as a routine diagnostic tool has proved to be difficult, however, primarily because of the stringent controls that are required for the method to be reproducible. The method is evolving as a powerful guide to the discovery of biomarkers that could, in turn, be used either individually or in an array or panel of tests for early disease detection. Using proteomic patterns to guide biomarker discovery and the possibility of deployment in the clinical laboratory environment on current instrumentation or in a hybrid technology has the possibility of being the early diagnosis tool that is needed. PMID:19389551

  3. Genome-wide serum microRNA expression profiling identifies serum biomarkers for Alzheimer's disease.

    PubMed

    Tan, Lin; Yu, Jin-Tai; Tan, Meng-Shan; Liu, Qiu-Yan; Wang, Hui-Fu; Zhang, Wei; Jiang, Teng; Tan, Lan

    2014-01-01

    Recent findings that human serum contains stably expressed microRNAs (miRNAs) have revealed a great potential of serum miRNA signature as disease fingerprints to diagnosis. Here we used genome-wide serum miRNA expression analysis to investigate the value of serum miRNAs as biomarkers for the diagnosis of Alzheimer's disease (AD). Illumina HiSeq 2000 sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between 50 AD patients and 50 controls in the screening stages. The detected serum miRNAs then were validated by qRT-PCR in 158 patients and 155 controls. MiR-98-5p, miR-885-5p, miR-483-3p, miR-342-3p, miR-191-5p, and miR-let-7d-5p displayed significantly different expression levels in AD patients compared with controls. Among the 6 miRNAs, miR-342-3p has the best sensitivity (81.5%) and specificity (70.1%) and was correlated to Mini-Mental State Examination score. This study identified six serum miRNAs that distinguish AD patients from healthy controls with high sensitivity and specificity. Serum miRNA panel (or miR-342-3p alone) may serve as a novel, noninvasive biomarker for AD.

  4. Identification and Insilico Analysis of Retinoblastoma Serum microRNA Profile and Gene Targets Towards Prediction of Novel Serum Biomarkers

    PubMed Central

    Beta, Madhu; Venkatesan, Nalini; Vasudevan, Madavan; Vetrivel, Umashankar; Khetan, Vikas; Krishnakumar, Subramanian

    2013-01-01

    Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient’s serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≤ −2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≥ +2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway. PMID:23400111

  5. Antibody microarray profiling of osteosarcoma cell serum for identifying potential biomarkers.

    PubMed

    Zhu, Zi-Qiang; Tang, Jin-Shan; Gang, Duan; Wang, Ming-Xing; Wang, Jian-Qiang; Lei, Zhou; Feng, Zhou; Fang, Ming-Liang; Yan, Lin

    2015-07-01

    The aim of the present study was to identify biomarkers in osteosarcoma (OS) cell serum by antibody microarray profiling, which may be used for OS diagnosis and therapy. An antibody microarray was used to detect the expression levels of cytokines in serum samples from 20 patients with OS and 20 healthy individuals. Significantly expressed cytokines in OS serum were selected when P<0.05 and fold change >2. An enzyme-linked immunosorbent assay (ELISA) was used to validate the antibody microarray results. Finally, classification accuracy was calculated by cluster analysis. Twenty one cytokines were significantly upregulated in OS cell serum samples compared with control samples. Expression of interleukin-6, monocyte chemoattractant protein-1, tumor growth factor-β, growth-related oncogene, hepatocyte growth factor, chemokine ligand 16, Endoglin, matrix metalloproteinase-9 and platelet-derived growth factor-AA was validated by ELISAs. OS serum samples and control samples were distinguished by significantly expressed cytokines with an accuracy of 95%. The results demonstrated that expressed cytokines identified by antibody microarray may be used as biomarkers for OS diagnosis and therapy.

  6. Antibody microarray profiling of osteosarcoma cell serum for identifying potential biomarkers.

    PubMed

    Zhu, Zi-Qiang; Tang, Jin-Shan; Gang, Duan; Wang, Ming-Xing; Wang, Jian-Qiang; Lei, Zhou; Feng, Zhou; Fang, Ming-Liang; Yan, Lin

    2015-07-01

    The aim of the present study was to identify biomarkers in osteosarcoma (OS) cell serum by antibody microarray profiling, which may be used for OS diagnosis and therapy. An antibody microarray was used to detect the expression levels of cytokines in serum samples from 20 patients with OS and 20 healthy individuals. Significantly expressed cytokines in OS serum were selected when P<0.05 and fold change >2. An enzyme-linked immunosorbent assay (ELISA) was used to validate the antibody microarray results. Finally, classification accuracy was calculated by cluster analysis. Twenty one cytokines were significantly upregulated in OS cell serum samples compared with control samples. Expression of interleukin-6, monocyte chemoattractant protein-1, tumor growth factor-β, growth-related oncogene, hepatocyte growth factor, chemokine ligand 16, Endoglin, matrix metalloproteinase-9 and platelet-derived growth factor-AA was validated by ELISAs. OS serum samples and control samples were distinguished by significantly expressed cytokines with an accuracy of 95%. The results demonstrated that expressed cytokines identified by antibody microarray may be used as biomarkers for OS diagnosis and therapy. PMID:25815525

  7. Serum Circulating microRNA Profiling for Identification of Potential Type 2 Diabetes and Obesity Biomarkers

    PubMed Central

    Pescador, Nuria; Pérez-Barba, Milagros; Ibarra, José María; Corbatón, Arturo; Martínez-Larrad, María Teresa; Serrano-Ríos, Manuel

    2013-01-01

    Background and Aim MicroRNAs are small non-coding RNAs that play important regulatory roles in a variety of biological processes, including complex metabolic processes, such as energy and lipid metabolism, which have been studied in the context of diabetes and obesity. Some particular microRNAs have recently been demonstrated to abundantly and stably exist in serum and to be potentially disease-specific. The aim of this profiling study was to characterize the expression of miRNA in serum samples of obese, nonobese diabetic and obese diabetic individuals to determine whether miRNA expression was deregulated in these serum samples and to identify whether any observed deregulation was specific to either obesity or diabetes or obesity with diabetes. Patients and Methods Thirteen patients with type 2 diabetes, 20 obese patients, 16 obese patients with type 2 diabetes and 20 healthy controls were selected for this study. MiRNA PCR panels were employed to screen serum levels of 739 miRNAs in pooled samples from these four groups. We compared the levels of circulating miRNAs between serum pools of each group. Individual validation of the twelve microRNAs selected as promising biomarkers was carried out using RT-qPCR. Results Three serum microRNAs, miR-138, miR-15b and miR-376a, were found to have potential as predictive biomarkers in obesity. Use of miR-138 or miR-376a provides a powerful predictive tool for distinguishing obese patients from normal healthy controls, diabetic patients, and obese diabetic patients. In addition, the combination of miR-503 and miR-138 can distinguish diabetic from obese diabetic patients. Conclusion This study is the first to show a panel of serum miRNAs for obesity, and compare them with miRNAs identified in serum for diabetes and obesity with diabetes. Our results support the use of some miRNAs extracted from serum samples as potential predictive tools for obesity and type 2 diabetes. PMID:24204780

  8. Dysregulated Serum MiRNA Profile and Promising Biomarkers in Dengue-infected Patients

    PubMed Central

    Ouyang, Xiaoxi; Jiang, Xin; Gu, Dayong; Zhang, Yaou; Kong, S.K.; Jiang, Chaoxin; Xie, Weidong

    2016-01-01

    Objectives: Pathological biomarkers and mechanisms of dengue infection are poorly understood. We investigated a new serum biomarker using miRNAs and performed further correlation analysis in dengue-infected patients. Methods: Expression levels of broad-spectrum miRNAs in serum samples from three patients with dengue virus type 1 (DENV-1) and three healthy volunteers were separately analyzed using miRNA PCR arrays. The expressions of the five selected miRNAs were verified by qRT-PCR in the sera of 40 DENV-1 patients and compared with those from 32 healthy controls. Receiver operating characteristic (ROC) curve and correlation analyses were performed to evaluate the potential of these miRNAs for the diagnosis of dengue infection. Results: MiRNA PCR arrays revealed that 41 miRNAs were upregulated, whereas 12 miRNAs were down-regulated in the sera of DENV-1 patients compared with those in healthy controls. Among these miRNAs, qRT-PCR validation showed that serum hsa-miR-21-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were upregulated, whereas hsa-miR-146a-5p was down-regulated in dengue-infected patients compared with healthy controls. ROC curves showed serum hsa-miR-21-5p and hsa-miR-146a-5p could distinguish dengue-infected patients with preferable sensitivity and specificity. Correlation analysis indicated that expression levels of serum hsa-miR-21-5p and hsa-miR-146a-5p were negative and positively correlated with the number of white blood cells and neutrophils, respectively. Functional analysis of target proteins of these miRNAs in silico indicated their involvement in inflammation and cell proliferation. Conclusion: Dengue-infected patients have a broad “fingerprint” profile with dysregulated serum miRNAs. Among these miRNAs, serum hsa-miR-21-5p, hsa-miR-146a-5p, hsa-miR-590-5p, hsa-miR-188-5p, and hsa-miR-152-3p were identified as promising serum indicators for dengue infection. PMID:26941580

  9. Investigation of long noncoding RNAs expression profile as potential serum biomarkers in patients with hepatocellular carcinoma.

    PubMed

    Kamel, Marwa M; Matboli, Marwa; Sallam, Maha; Montasser, Iman F; Saad, Amr S; El-Tawdi, Ahmed H F

    2016-02-01

    There is an increasing interest in using long noncoding RNAs (lncRNAs) as biomarkers in cancer. Predictive biomarkers in hepatocellular carcinoma (HCC) have great benefit in the choice of therapeutic modality for HCC. The aim of this study is to assess lncRNA-urothelial carcinoma associated-1 (lncRNA-UCA1) and WD repeat containing, antisense to TP53 (WRAP53) expression as novel noninvasive biomarkers for diagnosis of HCC in sera of HCC patients compared with chronic hepatitis C virus (HCV) patients and healthy volunteers and to analyze their relationship with respect to the clinicopathologic features. We retrieved HCC characteristic lncRNAs, lncRNA-UCA1 and lncRNA-WRAP53, based on the microarray signature profiling (released by LncRNADisease database). Quantitative reverse-transcriptase polymerase chain reaction assay (RT-qPCR) was then used to evaluate the expression of selected lncRNAs in the serum of 160 participants. Furthermore, in 20 of 82 HCC cases involved in the study, we examined the expression of lncRNA-UCA1 and lncRNA-WRAP53 in 20 HCC tissues and adjacent nontumor tissues and analyzed its correlation with the serum level of these lncRNAs. The prognostic significance of the investigated parameters in HCC patients was explored. We found that lncRNA-UCA1 and lncRNA-WRAP53 were significantly higher in sera of HCC than those with chronic HCV infection or healthy volunteers. Our data suggested that the increased expression of UCA1 and WRAP53 was associated with advanced clinical parameters in HCC. Of note, tissue levels of the chosen lncRNAs strongly correlate with their sera level. The combination of both lncRNAs with serum alpha fetoprotein resulted in improved sensitivity to 100%. The median follow-up period was 21.5 months. LncRNA-WRAP53 was significant independent prognostic markers in relapse-free survival. LncRNA-UCA1 and lncRNA-WRAP53 upregulation may serve as novel serum biomarkers for HCC diagnosis and prognosis. PMID:26551349

  10. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    PubMed

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar

    2016-02-01

    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration.

  11. Identification of novel biomarkers in chronic immune thrombocytopenia (ITP) by microarray-based serum protein profiling.

    PubMed

    Bal, Gürkan; Futschik, Matthias E; Hartl, Daniela; Ringel, Frauke; Kamhieh-Milz, Julian; Sterzer, Viktor; Hoheisel, Jörg D; Alhamdani, Mohamed S S; Salama, Abdulgabar

    2016-02-01

    The pathological mechanisms underlying the development of immune thrombocytopenia (ITP) are unclear and its diagnosis remains a process of exclusion. Currently, there are no known specific biomarkers for ITP to support differential diagnosis and treatment decisions. Profiling of serum proteins may be valuable for identifying such biomarkers. Sera from 46 patients with primary chronic ITP and 34 healthy blood donors were analysed using a microarray of 755 antibodies. We identified 161 differentially expressed proteins. In addition to oncoproteins and tumour-suppressor proteins, including apoptosis regulator BCL2, breast cancer type 1 susceptibility protein (BRCA1), Fanconi anaemia complementation group C (FANCC) and vascular endothelial growth factor A (VEGFA), we detected six anti-nuclear autoantibodies in a subset of ITP patients: anti-PCNA, anti-SmD, anti-Ro/SSA60, anti-Ro/SSA52, anti-La/SSB and anti-RNPC antibodies. This finding may provide a rational explanation for the association of ITP with malignancies and other autoimmune diseases. While RUNX1mRNA expression in the peripheral blood mononuclear cells (PBMC) of patients was significantly downregulated, an accumulation of RUNX1 protein was observed in the platelets of ITP patients. This may indicate dysregulation of RUNX1 expression in PBMC and megakaryocytes and may lead to an imbalanced immune response and impaired thrombopoiesis. In conclusion, we provide novel insights into the pathogenic mechanisms of ITP that warrant further exploration. PMID:26628061

  12. Multiple Serum Cytokine Profiling to Identify Combinational Diagnostic Biomarkers in Attacks of Familial Mediterranean Fever.

    PubMed

    Koga, Tomohiro; Migita, Kiyoshi; Sato, Shuntaro; Umeda, Masataka; Nonaka, Fumiaki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Masumoto, Junya; Agematsu, Kazunaga; Yachie, Akihiro; Yoshiura, Koh-Ichiro; Eguchi, Katsumi; Kawakami, Atsushi

    2016-04-01

    The precise cytokine networks in the serum of individuals with familial Mediterranean fever (FMF) that are associated with its pathogenesis have been unknown. Here, we attempted to identify specific biomarkers to diagnose or assess disease activity in FMF patients. We measured serum levels of 45 cytokines in 75 FMF patients and 40 age-matched controls by multisuspension cytokine array. FMF in "attack" or "remission" was classified by Japan College of Rheumatology-certified rheumatologists according to the Tel Hashomer criteria. Cytokines were ranked by their importance by a multivariate classification algorithm. We performed a logistic regression analysis to determine specific biomarkers for discriminating FMF patients in attack. To identify specific molecular networks, we performed a cluster analysis of each cytokine. Twenty-nine of the 45 cytokines were available for further analyses. Eight cytokines' serum levels were significantly elevated in the FMF attack versus healthy control group. Nine cytokines were increased in FMF attack compared to FMF remission. Multivariate classification algorithms followed by a logistic regression analysis revealed that the combined measurement of IL-6, IL-18, and IL-17 distinguished FMF patients in attack from the controls with the highest accuracy (sensitivity 89.2%, specificity 100%, and accuracy 95.5%). Among the FMF patients, the combined measurement of IL-6, G-CSF, IL-10, and IL-12p40 discriminated febrile attack periods from remission periods with the highest accuracy (sensitivity 75.0%, specificity 87.9%, and accuracy 84.0%). Our data identified combinational diagnostic biomarkers in FMF patients based on the measurement of multiple cytokines. These findings help to improve the diagnostic performance of FMF in daily practice and extend our understanding of the activation of the inflammasome leading to enhanced cytokine networks. PMID:27100444

  13. Differential expression profiling of serum proteins and metabolites for biomarker discovery

    NASA Astrophysics Data System (ADS)

    Roy, Sushmita Mimi; Anderle, Markus; Lin, Hua; Becker, Christopher H.

    2004-11-01

    A liquid chromatography-mass spectrometry (LC-MS) proteomics and metabolomics platform is presented for quantitative differential expression analysis. Proteome profiles obtained from 1.5 [mu]L of human serum show ~5000 de-isotoped and quantifiable molecular ions. Approximately 1500 metabolites are observed from 100 [mu]L of serum. Quantification is based on reproducible sample preparation and linear signal intensity as a function of concentration. The platform is validated using human serum, but is generally applicable to all biological fluids and tissues. The median coefficient of variation (CV) for ~5000 proteomic and ~1500 metabolomic molecular ions is approximately 25%. For the case of C-reactive protein, results agree with quantification by immunoassay. The independent contributions of two sources of variance, namely sample preparation and LC-MS analysis, are respectively quantified as 20.4 and 15.1% for the proteome, and 19.5 and 13.5% for the metabolome, for median CV values. Furthermore, biological diversity for ~20 healthy individuals is estimated by measuring the variance of ~6500 proteomic and metabolomic molecular ions in sera for each sample; the median CV is 22.3% for the proteome and 16.7% for the metabolome. Finally, quantitative differential expression profiling is applied to a clinical study comparing healthy individuals and rheumatoid arthritis (RA) patients.

  14. Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays

    PubMed Central

    Syed, Parvez; Gupta, Shabarni; Choudhary, Saket; Pandala, Narendra Goud; Atak, Apurva; Richharia, Annie; KP, Manubhai; Zhu, Heng; Epari, Sridhar; Noronha, Santosh B.; Moiyadi, Aliasgar; Srivastava, Sanjeeva

    2015-01-01

    The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing ~17000 full-length human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma. PMID:26370624

  15. Effects of cranberry powder on serum lipid profiles and biomarkers of oxidative stress in rats fed an atherogenic diet

    PubMed Central

    Kim, Mi Joung; Jung, Ha Na; Kim, Ki Nam

    2008-01-01

    This study investigated that the antioxidative effect of freeze-dried cranberry powder against protein and lipid oxidation and ameliorative effect of serum lipid profile in rat fed atherogenic diet. Six weeks old male Sprague-Dawley rats were divided into the following four groups: normal diet group with 5% corn oil (control), atherogenic diet group with 5% corn oil, 10% lard, 1% cholesterol, and 0.5% sodium cholate (HFC), atherogenic plus 2% cranberry powder diet group (HFC + C2), and atherogenic plus 5% cranberry powder diet group (HFC + C5), and respective diet and water were fed daily for 6 weeks. After the experimental period, the serum lipid profile, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride, ferric reducing ability of plasma (FRAP), plasma phenolics content, superoxide dismutase (SOD) activity, serum protein carbonyl and thiobarbituric acid reactive substances (TBARS) levels were examined. Total phenolic compound and total flavonoid levels in freeze-dried cranberry powder were 9.94 mg/g and 8.12 mg/g, respectively. Serum total cholesterol and LDL-cholesterol levels were not significantly different for cranberry powder treatment, but serum HDL-cholesterol level was significantly increased in HFC + C5 group compared with HFC group. Plasma FRAP value tended to be increased by cranberry powder treatment though there was no significant difference. Plasma total phenol concentrations and SOD activities were not significantly different among all groups. Serum protein carbonyl and TBARS levels were significantly decreased in HFC + C5 group compared with HFC group. Overall results suggested that freeze-dried cranberry powder might have the serum lipid improving effect, as well as antioxidative effect demonstrated by its protective effect against protein and lipid oxidation. PMID:20126601

  16. The effect of tick infestation on the serum concentrations of the cardiac biomarker troponin I, acid-base balance and haematobiochemical profiles in camels (Camelus dromedarius).

    PubMed

    Tharwat, Mohamed; Al-Sobayil, Fahd

    2014-01-01

    The aim of the present study was to evaluate the serum concentration of cardiac troponin I (cTnI) in camels with tick infestation as a marker of potential myocardial injury and its prognostication. The effects of acid-base and electrolyte balance and haematobiochemical profiles were also investigated. Twenty-three camels (Camelus dromedarius) with tick infestation and suffering from anorexia, incoordination of movement, unsteady gait, recumbency, opisthotonus, anaemia and reduced production were examined. Ticks were visible, deeply embedded in the skin over the whole body, especially under the neck and around the udder or testis. Of the camels, 15 recovered after treatment and 8 did not. Blood samples were collected from the diseased camels on the day of admission to our clinic. Blood samples were also collected from 12 healthy camels and were used as controls. The mean serum concentration of cTnI in the camels with tick infestation was 1.7 ± 1.6 ng/ml compared to 0.03 ± 0.02 ng/ml in the controls. The mean serum concentration of cTnI in those camels that recovered was 0.36 ± 0.53 ng/ml compared to 3.0 ± 1.1 ng/ml in the camels that did not. Venous blood gas alterations included an increase in partial pressure of carbon dioxide and decreases in partial pressure of oxygen and oxygen saturation. Haematological parameters involved decreases of red blood cells, haemoglobin and haematocrit and increases in the mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. Biochemical parameters included significant elevations in the serum activity of aspartate aminotransferase, creatine kinase and alkaline phosphates. Other biochemical alterations observed were decreases in total protein and albumin and increases in globulin and glucose concentrations. In conclusion, the data of this study suggest the possibility of using cTnI as a biomarker for cardiac injury in camels with tick infestation and for the

  17. Tissue imaging and serum lipidomic profiling for screening potential biomarkers of thyroid tumors by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Guo, Shuai; Qiu, Ling; Wang, Yanming; Qin, Xuzhen; Liu, Hui; He, Manwen; Zhang, Yaping; Li, Zhili; Chen, Xiaohong

    2014-07-01

    Changes in serum lipidome and in tissue lipidome are associated with cancer. In this study, tissue mass spectrometry imaging (MSI) and serum lipid profiling by matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS) were performed to investigate significantly changed lipids in both tumor (malignant thyroid cancer (MTC) and benign thyroid tumor (BTT)) tissues and sera. Y-scatterplots of variable importance in the projection (VIP) values vs. fold change values indicate that change trends in the levels of ten lipids (i.e., phosphatidylcholine (PC)(34:1), PC(36:1), PC(38:6), phosphatidic acid (PA) (36:2), PA(36:3), PA(38:3), PA(38:4), PA(38:5), PA(40:5), and sphingomyelin (SM)(34:1)) in both tissues and sera from MTC patients, BTT patients, and normal individuals are significantly associated with these three types of pathophysiological status. In order to examine their diagnostic ability, 289 serum samples from 124 MTC patients, 43 BTT patients, and 122 normal controls were randomly divided into the training set and validation set. A biomarker of PC(34:1) exhibited excellent diagnostic ability to differentiate both MTC and BTT patients from normal individuals, with an area under the receiver operating characteristic (ROC) curve value of 0.984, a sensitivity of 96.4 %, and a specificity of 92.7 %. A panel which included PA(36:3) and SM(34:1) could distinguish between MTC and BTT, with an area under receiver operating characteristic curve (AUC) of 0.961, a sensitivity of 87.8 %, and a specificity of 92.9 %. It is worth noting that a panel consisting of PC(34:1), PA(36:3), and SM(34:1) could differentiate MTC patients from both BTT patients and normal individuals, with an AUC of 0.841, a sensitivity of 86.6 %, and a specificity of 75.5 %.

  18. Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma.

    PubMed

    Qi, Yi-Jun; Ward, Douglas G; Pang, Chun; Wang, Qi-Ming; Wei, Wenbin; Ma, Jin; Zhang, Juan; Lou, Qiang; Shimwell, Neil J; Martin, Ashley; Wong, Nathalie; Chao, Wei-Xia; Wang, Ming; Ma, Yuan-Fang; Johnson, Philip J

    2014-02-01

    The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC.

  19. Serum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients.

    PubMed

    Jeanson-Leh, Laurence; Lameth, Julie; Krimi, Soraya; Buisset, Julien; Amor, Fatima; Le Guiner, Caroline; Barthélémy, Inès; Servais, Laurent; Blot, Stéphane; Voit, Thomas; Israeli, David

    2014-11-01

    Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.

  20. SERUM BIOMARKERS OF AGING IN THE BROWN NORWAY RAT

    EPA Science Inventory

    Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomark...

  1. Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

    PubMed Central

    Chen, Qiuying; Deeb, Ruba S.; Ma, Yuliang; Staudt, Michelle R.; Crystal, Ronald G.; Gross, Steven S.

    2015-01-01

    COPD (chronic obstructive pulmonary disease) is defined by a fixed expiratory airflow obstruction associated with disordered airways and alveolar destruction. COPD is caused by cigarette smoking and is the third greatest cause of mortality in the US. Forced expiratory volume in 1 second (FEV1) is the only validated clinical marker of COPD, but it correlates poorly with clinical features and is not sensitive enough to predict the early onset of disease. Using LC/MS global untargeted metabolite profiling of serum samples from a well-defined cohort of healthy smokers (n = 37), COPD smokers (n = 41) and non-smokers (n = 37), we sought to discover serum metabolic markers with known and/or unknown molecular identities that are associated with early-onset COPD. A total of 1,181 distinct molecular ions were detected in 95% of sera from all study subjects and 23 were found to be differentially-expressed in COPD-smokers vs. healthy-smokers. These 23 putative biomarkers were differentially-correlated with lung function parameters and used to generate a COPD prediction model possessing 87.8% sensitivity and 86.5% specificity. In an independent validation set, this model correctly predicted COPD in 8/10 individuals. These serum biomarkers included myoinositol, glycerophopshoinositol, fumarate, cysteinesulfonic acid, a modified version of fibrinogen peptide B (mFBP), and three doubly-charged peptides with undefined sequence that significantly and positively correlate with mFBP levels. Together, elevated levels of serum mFBP and additional disease-associated biomarkers point to a role for chronic inflammation, thrombosis, and oxidative stress in remodeling of the COPD airways. Serum metabolite biomarkers offer a promising and accessible window for recognition of early-stage COPD. PMID:26674646

  2. New serum biomarkers for prostate cancer diagnosis

    PubMed Central

    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

  3. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer.

    PubMed

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-03-15

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC).We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression.Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  4. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer

    PubMed Central

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-01-01

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression. Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  5. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children.

    PubMed

    Hathout, Yetrib; Conklin, Laurie S; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J; Morgenroth, Lauren P; Nagaraju, Kanneboyina; Heier, Christopher R; Damsker, Jesse M; van den Anker, John N; Henricson, Erik; Clemens, Paula R; Mah, Jean K; McDonald, Craig; Hoffman, Eric P

    2016-08-17

    Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes.

  6. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children.

    PubMed

    Hathout, Yetrib; Conklin, Laurie S; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J; Morgenroth, Lauren P; Nagaraju, Kanneboyina; Heier, Christopher R; Damsker, Jesse M; van den Anker, John N; Henricson, Erik; Clemens, Paula R; Mah, Jean K; McDonald, Craig; Hoffman, Eric P

    2016-01-01

    Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes. PMID:27530235

  7. Serum pharmacodynamic biomarkers for chronic corticosteroid treatment of children

    PubMed Central

    Hathout, Yetrib; Conklin, Laurie S.; Seol, Haeri; Gordish-Dressman, Heather; Brown, Kristy J.; Morgenroth, Lauren P.; Nagaraju, Kanneboyina; Heier, Christopher R.; Damsker, Jesse M.; van den Anker, John N.; Henricson, Erik; Clemens, Paula R.; Mah, Jean K.; McDonald, Craig; Hoffman, Eric P.

    2016-01-01

    Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes. PMID:27530235

  8. Liquid Chromatography-Mass Spectrometry (LC/MS)-based parallel metabolic profiling of human and mouse model serum reveals putative biomarkers associated with the progression of non-alcoholic fatty liver disease

    PubMed Central

    Barr, Jonathan; Alonso, Cristina; Vázquez-Chantada, Mercedes; Cormenzana, Miriam Pérez-; Mayo, Rebeca; Galán, Asier; Caballería, Juan; Martín-Duce, Antonio; Tran, Albert; Wagner, Conrad; Luka, Zigmund; Lu, Shelly C.; Castro, Azucena; Le Marchand-Brustel, Yannick; Martínez-Chantar, M. Luz; Veyrie, Nicolas; Clément, Karine; Tordjman, Joan; Gual, Philippe; Mato, José M.

    2010-01-01

    Non-alcoholic fatty liver disease (NAFLD), is the most common form of chronic liver disease in most western countries. Current NAFLD diagnosis methods (e.g. liver biopsy analysis or imaging techniques) are poorly suited as tests for such a prevalent condition, from both a clinical and financial point of view. The present work aims to demonstrate the potential utility of serum metabolic profiling in defining phenotypic biomarkers that could be useful in NAFLD management. A parallel animal model / human NAFLD exploratory metabolomics approach was employed, using ultra performance liquid chromatography-mass spectrometry (UPLC®-MS) to analyze 42 serum samples collected from non-diabetic, morbidly obese, biopsy-proven NAFLD patients, and 17 animals belonging to the glycine N-methyltransferase knockout (GNMT-KO) NAFLD mouse model. Multivariate statistical analysis of the data revealed a series of common biomarkers that were significantly altered in the NAFLD (GNMT-KO) subjects in comparison to their normal liver counterparts (WT). Many of the compounds observed could be associated with biochemical perturbations associated with liver dysfunction (e.g. reduced Creatine) and inflammation (e.g. eicosanoid signaling). This differential metabolic phenotyping approach may have a future role as a supplement for clinical decision making in NAFLD and in the adaption to more individualized treatment protocols. PMID:20684516

  9. Serum and tissue biomarkers in aortic stenosis

    PubMed Central

    Kapelouzou, Alkistis; Tsourelis, Loukas; Kaklamanis, Loukas; Degiannis, Dimitrios; Kogerakis, Nektarios; Cokkinos, Dennis V.

    2015-01-01

    Background: Calcific aortic valve stenosis (CAVS) is seen in a large proportion of individuals over 60 years. It is an active process, influenced by lipid accumulation, mechanical stress, inflammation, and abnormal extracellular matrix turnover. Various biomarkers (BMs) are studied, as regards mechanisms, diagnosis and prognosis. Methods: In the calcified valves calcium deposition, elastin fragmentation and disorganization of cellular matrix were assessed, together with expression of OPN, OPG, osteocalcin (OCN) and RL2. We prospectively studied the following serum BMs in 60 patients with CAVS and compared them to 20 healthy controls, free from any cardiac disease: Matrix metalloproteinases (MMP) 2 and 9 and tissue inhibitor of metalloproteinase 1 (TIMP1), which regulate collagen turnover, inflammatory factors, i.e. tumor necrosis factor a (TNFa), interleukin 2 (IL2), transforming growth factor β1 (TGF-β1) which regulates fibrosis, fetuin-A (fet-A), osteopontin (OPN), osteoprotegerin (OPG), sclerostin (SOST), and relaxin-2 (RL2) which positively or negatively regulate calcification. Monocyte chemoattractant protein 1 (MCP-1) which regulates migration and infiltration of monocytes/macrophages was also studied as well as malondialdehyde (MDA) an oxidative marker. Results: Extent of tissue valve calcification (Alizarin Red stain) was negatively correlated with tissue elastin, and RL2, and positively correlated with tissue OCN and serum TIMP1 and MCP-1 and negatively with MMP9. Tissue OCN was positively correlated with OPN and negatively with the elastin. Tissue OPN was negatively correlated with elastin and OPG. Tissue OPN OPG and RL2 were not correlated with serum levels In the serum we found in patients statistically lower TIMP1, fet-A and RL2 levels, while all other BMs were higher compared to the healthy group. Positive correlations between SOST and IL2, OPG and MDA but negative with TNFa and OPN were found; also MMP9 was negatively correlated with TNFa and MCP-1

  10. Serum biomarker panels for diagnosis of gastric cancer

    PubMed Central

    Tong, Weihua; Ye, Fei; He, Liang; Cui, Lifeng; Cui, Miao; Hu, Yuan; Li, Wei; Jiang, Jing; Zhang, David Y; Suo, Jian

    2016-01-01

    Purpose Currently, serum biomarkers that are sufficiently sensitive and specific for early detection and risk classification of gastric adenocarcinomas are not known. In this study, ten serum markers were assessed using the Luminex system and enzyme-linked immunosorbent assay for the diagnosis of gastric cancer and analysis of the relation between prognosis and metastases. Patients and methods A training set consisting of 228 gastric adenocarcinoma and 190 control samples was examined. A Luminex multiplex panel with nine biomarkers, consisting of three proteins discovered through our previous studies and six proteins previously reported to be cancer-associated, was constructed. One additional biomarker was detected using a commercial kit containing EDTA. Logistic regression, random forest (RF), and support vector machine (SVM) were used to identify the panel of discriminatory biomarkers in the training set. After selecting five proteins as candidate biomarkers, multivariate classification analyses were used to identify algorithms for diagnostic biomarker combinations. These algorithms were independently validated using a set of 57 gastric adenocarcinoma and 48 control samples. Results Serum pepsinogen I, serum pepsinogen II, A Disintegrin And Metalloproteinase domain-containing protein 8 (ADAM8), vascular endothelial growth factor (VEGF), and serum IgG to Helicobacter pylori were selected as classifiers in the three algorithms. These algorithms differentiated between the majority of gastric adenocarcinoma and control serum samples in the training/test set with high accuracy (RF 79.0%, SVM 83.8%, logistic regression 76.2%). These algorithms also differentiated the samples in the validation set (accuracy: RF 82.5%, SVM 86.1%, logistic regression 78.7%). Conclusion A panel of combinatorial biomarkers comprising VEGF, ADAM8, IgG to H. pylori, serum pepsinogen I, and pepsinogen II were developed. The use of biomarkers is a less invasive method for the diagnosis of

  11. Serum proteomic profiling of major depressive disorder

    PubMed Central

    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

  12. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics

    PubMed Central

    Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E.; Joshi, Lokesh; Kilcoyne, Michelle

    2015-01-01

    Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques. PMID:26509158

  13. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

    PubMed

    Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

    2015-01-01

    Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

  14. Serum proteomics for biomarker discovery in nonalcoholic fatty liver disease.

    PubMed

    Yilmaz, Yusuf

    2012-08-16

    Proteomic platforms have gained increasing attention in the clinical spectrum of nonalcoholic fatty liver disease (NAFLD). This approach allows for the unbiased discovery of circulating biochemical markers, i.e., it is not limited to known molecules of presumed importance. This manuscript provides an overview of proteomic serum biomarker discovery in NAFLD. Hemoglobin is currently the most widely replicated proteomic circulating biomarker of NAFLD; it was identified as a biomarker of fatty liver in two distinct proteomic studies and subsequently validated using distinct analytical methods by independent research groups in large replication cohorts. Given the increasing availability of numerous serum samples and the refinement of the technological platforms available to scrutinize the blood proteome, large collaborative studies between academia and industry are warmly encouraged to identify novel, unbiased circulating biomarkers of NAFLD.

  15. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    PubMed

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  16. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker.

    PubMed

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer.

  17. REG4 Is Highly Expressed in Mucinous Ovarian Cancer: A Potential Novel Serum Biomarker

    PubMed Central

    Lehtinen, Laura; Vesterkvist, Pia; Roering, Pia; Korpela, Taina; Hattara, Liisa; Kaipio, Katja; Mpindi, John-Patrick; Hynninen, Johanna; Auranen, Annika; Davidson, Ben; Haglund, Caj; Iljin, Kristiina; Grenman, Seija; Siitari, Harri; Carpen, Olli

    2016-01-01

    Preoperative diagnostics of ovarian neoplasms rely on ultrasound imaging and the serum biomarkers CA125 and HE4. However, these markers may be elevated in non-neoplastic conditions and may fail to identify most non-serous epithelial cancer subtypes. The objective of this study was to identify histotype-specific serum biomarkers for mucinous ovarian cancer. The candidate genes with mucinous histotype specific expression profile were identified from publicly available gene-expression databases and further in silico data mining was performed utilizing the MediSapiens database. Candidate biomarker validation was done using qRT-PCR, western blotting and immunohistochemical staining of tumor tissue microarrays. The expression level of the candidate gene in serum was compared to the serum CA125 and HE4 levels in a patient cohort of prospectively collected advanced ovarian cancer. Database searches identified REG4 as a potential biomarker with specificity for the mucinous ovarian cancer subtype. The specific expression within epithelial ovarian tumors was further confirmed by mRNA analysis. Immunohistochemical staining of ovarian tumor tissue arrays showed distinctive cytoplasmic expression pattern only in mucinous carcinomas and suggested differential expression between benign and malignant mucinous neoplasms. Finally, an ELISA based serum biomarker assay demonstrated increased expression only in patients with mucinous ovarian cancer. This study identifies REG4 as a potential serum biomarker for histotype-specific detection of mucinous ovarian cancer and suggests serum REG4 measurement as a non-invasive diagnostic tool for postoperative follow-up of patients with mucinous ovarian cancer. PMID:26981633

  18. Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies

    PubMed Central

    Rouillon, Jérémy; Poupiot, Jérôme; Zocevic, Aleksandar; Amor, Fatima; Léger, Thibaut; Garcia, Camille; Camadro, Jean-Michel; Wong, Brenda; Pinilla, Robin; Cosette, Jérémie; Coenen-Stass, Anna M.L.; Mcclorey, Graham; Roberts, Thomas C.; Wood, Matthew J.A.; Servais, Laurent; Udd, Bjarne; Voit, Thomas; Richard, Isabelle; Svinartchouk, Fedor

    2015-01-01

    Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the myofibrillar structural protein myomesin-3 (MYOM3) are abnormally present in sera of Duchenne muscular dystrophy (DMD) patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels. In the LGMD model, where different doses of vector were used, MYOM3 restoration was dose-dependent. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders. PMID:26060189

  19. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    PubMed Central

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  20. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma.

    PubMed

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  1. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    NASA Astrophysics Data System (ADS)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347–356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205–214), and isoform 1 of fibrinogen α chain precursor (FGA 588–624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  2. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach.

    PubMed

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-01-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  3. Serum amino acid profiles and their alterations in colorectal cancer.

    PubMed

    Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin

    2012-08-01

    Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.

  4. Serum Biomarkers of (Anti)Oxidant Status for Epidemiological Studies

    PubMed Central

    Jansen, Eugène; Ruskovska, Tatjana

    2015-01-01

    In this review, we disclose a selection of serum/plasma biomarkers of (anti)oxidant 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, (anti)oxidant 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. PMID:26580612

  5. Immunoproteomic Analysis of Potential Serum Biomarker Candidates in Human Glaucoma

    PubMed Central

    Tezel, Gülgün; Thornton, Ivey L.; Tong, Melissa G.; Luo, Cheng; Yang, Xiangjun; Cai, Jian; Powell, David W.; Soltau, Joern B.; Liebmann, Jeffrey M.; Ritch, Robert

    2012-01-01

    Purpose. Evidence supporting the immune system involvement in glaucoma includes increased titers of serum antibodies to retina and optic nerve proteins, although their pathogenic importance remains unclear. This study using an antibody-based proteomics approach aimed to identify disease-related antigens as candidate biomarkers of glaucoma. Methods. Serum samples were collected from 111 patients with primary open-angle glaucoma and an age-matched control group of 49 healthy subjects without glaucoma. For high-throughput characterization of antigens, serum IgG was eluted from five randomly selected glaucomatous samples and analyzed by linear ion trap mass spectrometry (LC-MS/MS). Serum titers of selected biomarker candidates were then measured by specific ELISAs in the whole sample pool (including an additional control group of diabetic retinopathy). Results. LC-MS/MS analysis of IgG elutes revealed a complex panel of proteins, including those detectable only in glaucomatous samples. Interestingly, many of these antigens corresponded to upregulated retinal proteins previously identified in glaucomatous donors (or that exhibited increased methionine oxidation). Moreover, additional analysis detected a greater immunoreactivity of the patient sera to glaucomatous retinal proteins (or to oxidatively stressed cell culture proteins), thereby suggesting the importance of disease-related protein modifications in autoantibody production/reactivity. As a narrowing-down strategy for selection of initial biomarker candidates, we determined the serum proteins overlapping with the retinal proteins known to be up-regulated in glaucoma. Four of the selected 10 candidates (AIF, cyclic AMP-responsive element binding protein, ephrin type-A receptor, and huntingtin) exhibited higher ELISA titers in the glaucomatous sera. Conclusions. A number of serum proteins identified by this immunoproteomic study of human glaucoma may represent diseased tissue-related antigens and serve as candidate

  6. Serum Protein Profile Alterations in Hemodialysis Patients

    SciTech Connect

    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. Identification of novel serum peptides biomarkers for female breast cancer patients in Western China.

    PubMed

    Yang, Juan; Xiong, Xiaofan; Liu, Siyuan; Zhu, Jiang; Luo, Mai; Liu, Liying; Zhao, Lingyu; Qin, Yannan; Song, Tusheng; Huang, Chen

    2016-03-01

    This study aimed to identify novel serum peptides biomarkers for female breast cancer (BC) patients. We analyzed the serum proteomic profiling of 247 serum samples from 96 BC patients, 48 additional paired pre- and postoperative BC patients, 39 fibroadenoma patients as benign disease controls, and 64 healthy controls, using magnetic-bead-based separation followed by MALDI-TOF MS. ClinProTools software identified 78 m/z peaks that differed among all analyzed groups, ten peaks were significantly different (P < 0.0001), with Peaks 1-6 upregulated and Peaks 7-10 downregulated in BC. Moreover, three peaks of ten (Peak 1, m/z: 2660.11; Peak 2, m/z: 1061.09; Peak 10, m/z: 1041.25) showed a tendency to return to healthy control values after surgery. And these three peptide biomarkers were identified as FGA605-629, ITIH4 347-356, and APOA2 43-52. Methods used in this study could generate serum peptidome profiles of BC, and provide a new approach to identify potential biomarkers for diagnosis as well as prognosis of this malignancy. PMID:26705257

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

    PubMed

    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.

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

    PubMed

    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. PMID:26687614

  10. The Current State of Clinical Application of Serum Biomarkers for Canine Lymphoma

    PubMed Central

    Bryan, Jeffrey N.

    2016-01-01

    Serum biomarkers of canine lymphoma activity for diagnosis, prognosis, and therapy monitoring have been of clinical interest for more than a decade. Tumor products, biochemical enzymes, cytokines, metabolic profiling, leakage enzymes, as well as serum proteins have been studied as biomarkers for lymphoma. Multiple biomarkers combined have been shown to be most sensitive and specific. C-reactive protein, thymidine kinase 1, and haptoglobin have been most extensively studied and commercialized in diagnostic tests, the TK Canine Cancer Panel and the Canine Lymphoma Blood Test. These tests have been evaluated either in cohorts of diseased and healthy dogs or in prospective studies of ill dogs, respectively, for application to clinical decision-making. Some evidence exists for application of these tests, but large-scale studies are lacking in a broad range of lymphoma forms. These biomarkers are commonly elevated at diagnosis and at relapse. Further study is necessary to determine if early intervention guided by biomarker elevation will improve quantity or quality of life for dogs with lymphoma. PMID:27747218

  11. Serum Metabolomic Profiling of Rats by Intervention of Aconitum soongaricum.

    PubMed

    Zhang, Fan; Liu, Jiao; Lei, Jun; He, Wenjing; Sun, Yun

    2015-12-01

    To understand the toxic mechanism and to find the changes in the endogenous metabolites of Aconitum soongaricum Stapf for clinical detection, a combination of 1H NMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the blood serum samples collected from the rat model. In total, thirteen biomarkers of A. soongaricum were found and identified. It turned out that A. soongaricum treatment may partially disorder the metabolism. The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the toxicity caused by A. soongaricum. PMID:26882691

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

    SciTech Connect

    Moser, Virginia C.; McMahen, Rebecca L.; Strynar, Mark J.; Herr, David W.

    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

  13. SERUM PROTEIN PROFILES IN COCCIDIOIDOMYCOSIS

    PubMed Central

    Reed, William B.; Heiskell, Charles L.; Holeman, Charles W.; Carpenter, Charles

    1962-01-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response. PMID:13973566

  14. Serum protein profiles in coccidioidomycosis.

    PubMed

    REED, W B; HEISKELL, C L; HOLEMAN, C W; CARPENTER, C

    1962-12-01

    Serum protein analysis is a valuable addition to the present methods for evaluating the status of the individual patient with coccidioidomycosis. The albumin protein and albumin glycoprotein decrease and gamma protein increases in relation to severity of infection. In 40 patients with coccidioidomycosis, changes in individual protein fractions could be significantly correlated with conventional laboratory tests, such as the complement fixation test, erythrocyte sedimentation rate and hematocrit. Changes in the alpha, glycoprotein concentration, the erythrocyte sedimentation rate and the hematocrit value appear to be related to the degree of inflammation, while the changes in the gamma protein and the beta, glycoprotein appear to be related to the specific antibody response.

  15. Serum Leptin Is a Biomarker of Malnutrition in Decompensated Cirrhosis

    PubMed Central

    Rachakonda, Vikrant; Borhani, Amir A.; Dunn, Michael A.; Andrzejewski, Margaret; Martin, Kelly; Behari, Jaideep

    2016-01-01

    Background and Aims Malnutrition is a leading cause of morbidity and mortality in cirrhosis. There is no consensus as to the optimal approach for identifying malnutrition in end-stage liver disease. The aim of this study was to measure biochemical, serologic, hormonal, radiographic, and anthropometric features in a cohort of hospitalized cirrhotic patients to characterize biomarkers for identification of malnutrition. Design In this prospective observational cohort study, 52 hospitalized cirrhotic patients were classified as malnourished (42.3%) or nourished (57.7%) based on mid-arm muscle circumference < 23 cm and dominant handgrip strength < 30 kg. Anthropometric measurements were obtained. Appetite was assessed using the Simplified Nutrition Appetite Questionnaire (SNAQ) score. Fasting levels of serum adipokines, cytokines, and hormones were determined using Luminex assays. Logistic regression analysis was used to determine features independently associated with malnutrition. Results Subjects with and without malnutrition differed in several key features of metabolic phenotype including wet and dry BMI, skeletal muscle index, visceral fat index and HOMA-IR. Serum leptin levels were lower and INR was higher in malnourished subjects. Serum leptin was significantly correlated with HOMA-IR, wet and dry BMI, mid-arm muscle circumference, skeletal muscle index, and visceral fat index. Logistic regression analysis revealed that INR and log-transformed leptin were independently associated with malnutrition. Conclusions Low serum leptin and elevated INR are associated with malnutrition in hospitalized patients with end-stage liver disease. PMID:27583675

  16. Extensive serum biomarker analysis in patients with ST segment elevation myocardial infarction (STEMI).

    PubMed

    Zhang, Yi; Lin, Peiyi; Jiang, Huilin; Xu, Jieling; Luo, Shuhong; Mo, Junrong; Li, Yunmei; Chen, Xiaohui

    2015-12-01

    ST segment elevation myocardial infarction (STEMI) is one of the leading causes of morbidity and mortality and some characteristics of STEMI are poorly understood. The aim of the present study is to detect protein expression profiles in the serum of STEMI patients, and to identify biomarkers for this disease. Cytokine profiles of serum from STEMI patients and healthy controls were analyzed with a semi-quantitative human antibody array for 174 proteins, and the results showed blood serum concentrations of 21 cytokines differed considerably between STEMI patients and healthy subjects. In the next phase, a sandwich ELISA kit individually validated eight biomarker results from 21 of the microarray experiments. Clinical validation demonstrated a significant increase of BNDF, PDGF-AA and MMP-9 in patients with AMI. Meanwhile, BNDF, PDGF-AA and MMP-9 distinguished AMI patients from healthy controls with a mean area under the receiver operating characteristic (ROC) curves of 0.870, 0.885, and 0.81, respectively, with diagnostic cut-off points of 0.688 ng/mL, 297.86 ng/mL and 690.066 ng/mL. Our study indicated that these three cytokines were up-regulated in STEMI samples, and may hold promise for the assessment of STEMI.

  17. Identification of Candidate Serum Biomarkers for Schistosoma mansoni Infected Mice Using Multiple Proteomic Platforms

    PubMed Central

    Kardoush, Manal I.

    2016-01-01

    Background Schistosomiasis is an important helminth infection of humans. There are few reliable diagnostic biomarkers for early infection, for recurrent infection or to document successful treatment. In this study, we compared serum protein profiles in uninfected and infected mice to identify disease stage-specific biomarkers. Methods Serum collected from CD1 mice infected with 50–200 Schistosoma mansoni cercariae were analyzed before infection and at 3, 6 and 12 weeks post-infection using three mass spectrometric (MS) platforms. Results Using SELDI-TOF MS, 66 discriminating m/z peaks were detected between S. mansoni infected mice and healthy controls. Used in various combinations, these peaks could 1) reliably diagnose early-stage disease, 2) distinguish between acute and chronic infection and 3) diagnose S. mansoni infection regardless the parasite burden. The most important contributors to these diagnostic algorithms were peaks at 3.7, 13 and 46 kDa. Employing sample fractionation and differential gel electrophoresis, we analyzed gel slices either by MALDI-TOF MS or Velos Orbitrap MS. The former yielded eight differentially-expressed host proteins in the serum at different disease stages including transferrin and alpha 1- antitrypsin. The latter suggested the presence of a surprising number of parasite-origin proteins in the serum during both the acute (n = 200) and chronic (n = 105) stages. The Orbitrap platform also identified many differentially-expressed host-origin serum proteins during the acute and chronic stages (296 and 220 respectively). The presence of one of the schistosome proteins, glutathione S transferase (GST: 25 KDa), was confirmed by Western Blot. This study provides proof-of-principle for an approach that can yield a large number of novel candidate biomarkers for Schistosoma infection. PMID:27138990

  18. Ultrasensitive Rapid Detection of Human Serum Antibody Biomarkers by Biomarker-Capturing Viral Nanofibers

    PubMed Central

    Cao, Binrui; Gao, Xiang; Zhu, Ye; Qiu, Penghe; Xu, Hong; Pan, Pengtao; Bao, Huizheng; Wang, Li; Mao, Chuanbin

    2016-01-01

    Candida albicans (C. albicans) infection causes high mortality rates within cancer patients. Due to the low sensitivity of the current diagnosis systems, a new sensitive detection method is needed for its diagnosis. Toward this end, here we exploited the capability of genetically displaying two functional peptides, one responsible for recognizing the biomarker for the infection (antisecreted aspartyl proteinase 2 IgG antibody) in the sera of cancer patients and another for binding magnetic nanoparticles (MNPs), on a single filamentous fd phage, a human-safe bacteria-specific virus. The resultant phage is first decorated with MNPs and then captures the biomarker from the sera. The phage-bound biomarker is then magnetically enriched and biochemically detected. This method greatly increases the sensitivity and specificity of the biomarker detection. The average detection time for each serum sample is only about 6 h, much shorter than the clinically used gold standard method, which takes about 1 week. The detection limit of our nanobiotechnological method is approximately 1.1 pg/mL, about 2 orders of magnitude lower than that of the traditional antigen-based method, opening up a new avenue to virus-based disease diagnosis. PMID:25855864

  19. Ultrasensitive rapid detection of human serum antibody biomarkers by biomarker-capturing viral nanofibers.

    PubMed

    Wang, Yicun; Ju, Zhigang; Cao, Binrui; Gao, Xiang; Zhu, Ye; Qiu, Penghe; Xu, Hong; Pan, Pengtao; Bao, Huizheng; Wang, Li; Mao, Chuanbin

    2015-01-01

    Candida albicans (C. albicans) infection causes high mortality rates within cancer patients. Due to the low sensitivity of the current diagnosis systems, a new sensitive detection method is needed for its diagnosis. Toward this end, here we exploited the capability of genetically displaying two functional peptides, one responsible for recognizing the biomarker for the infection (antisecreted aspartyl proteinase 2 IgG antibody) in the sera of cancer patients and another for binding magnetic nanoparticles (MNPs), on a single filamentous fd phage, a human-safe bacteria-specific virus. The resultant phage is first decorated with MNPs and then captures the biomarker from the sera. The phage-bound biomarker is then magnetically enriched and biochemically detected. This method greatly increases the sensitivity and specificity of the biomarker detection. The average detection time for each serum sample is only about 6 h, much shorter than the clinically used gold standard method, which takes about 1 week. The detection limit of our nanobiotechnological method is approximately 1.1 pg/mL, about 2 orders of magnitude lower than that of the traditional antigen-based method, opening up a new avenue to virus-based disease diagnosis. PMID:25855864

  20. GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    EPA Science Inventory

    SOT 2005 SESSION ABSTRACT

    GENE EXPRESSION PROFILING TO IDENTIFY BIOMARKERS OF REPRODUCTIVE TOXICITY

    David J. Dix. National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle...

  1. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma.

    PubMed

    Shah, Alok K; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C; Saunders, Nicholas A; Barbour, Andrew P; Joshi, Virendra; Hill, Michelle M

    2015-11-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  2. Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma*

    PubMed Central

    Shah, Alok K.; Cao, Kim-Anh Lê; Choi, Eunju; Chen, David; Gautier, Benoît; Nancarrow, Derek; Whiteman, David C.; Saunders, Nicholas A.; Barbour, Andrew P.; Joshi, Virendra; Hill, Michelle M.

    2015-01-01

    We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di.uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (NPL)-reactive Apolipoprotein B-100 (p value = 0.0231; AUROC = 0.71); BE versus EAC, Aleuria aurantia lectin (AAL)-reactive complement component C9 (p value = 0.0001; AUROC = 0.85); healthy versus EAC, Erythroagglutinin Phaseolus vulgaris (EPHA)-reactive gelsolin (p value = 0.0014; AUROC = 0.80). A panel of 8 glycoforms showed an improved AUROC of 0.94 to discriminate EAC from BE. Two biomarker candidates

  3. Identification of Serum Biomarkers for Gastric Cancer Diagnosis Using a Human Proteome Microarray.

    PubMed

    Yang, Lina; Wang, Jingfang; Li, Jianfang; Zhang, Hainan; Guo, Shujuan; Yan, Min; Zhu, Zhenggang; Lan, Bin; Ding, Youcheng; Xu, Ming; Li, Wei; Gu, Xiaonian; Qi, Chong; Zhu, Heng; Shao, Zhifeng; Liu, Bingya; Tao, Sheng-Ce

    2016-02-01

    We aimed to globally discover serum biomarkers for diagnosis of gastric cancer (GC). GC serum autoantibodies were discovered and validated using serum samples from independent patient cohorts encompassing 1,401 participants divided into three groups, i.e. healthy, GC patients, and GC-related disease group. To discover biomarkers for GC, the human proteome microarray was first applied to screen specific autoantibodies in a total of 87 serum samples from GC patients and healthy controls. Potential biomarkers were identified via a statistical analysis protocol. Targeted protein microarrays with only the potential biomarkers were constructed and used to validate the candidate biomarkers using 914 samples. To provide further validation, the abundance of autoantibodies specific to the biomarker candidates was analyzed using enzyme-linked immunosorbent assays. Receiver operating characteristic curves were generated to evaluate the diagnostic accuracy of the serum biomarkers. Finally, the efficacy of prognosis efficacy of the final four biomarkers was evaluated by analyzing the clinical records. The final panel of biomarkers consisting of COPS2, CTSF, NT5E, and TERF1 provides high diagnostic power, with 95% sensitivity and 92% specificity to differentiate GC patients from healthy individuals. Prognosis analysis showed that the panel could also serve as independent predictors of the overall GC patient survival. The panel of four serum biomarkers (COPS2, CTSF, NT5E, and TERF1) could serve as a noninvasive diagnostic index for GC, and the combination of them could potentially be used as a predictor of the overall GC survival rate. PMID:26598640

  4. Serum Amyloid A as a Biomarker for Radiation Exposure

    PubMed Central

    Sproull, Mary; Kramp, Tamalee; Tandle, Anita; Shankavaram, Uma; Camphausen, Kevin

    2016-01-01

    There is a need for minimally invasive biomarkers that can accurately and quickly quantify radiation exposure. Radiation-responsive proteins have applications in clinical medicine and for mass population screenings after a nuclear or radiological incident where the level of radiation exposure and exposure pattern complicate medical triage for first responders. In this study, we evaluated the efficacy of the acute phase protein serum amyloid A (SAA) as a biomarker for radiation exposure using plasma from irradiated mice. Ten-week-old female C57BL6 mice received a 1–8 Gy single whole-body or partial-body dose from a Pantak X-ray source at a dose rate of 2.28 Gy/min. Plasma was collected by mandibular or cardiac puncture at 6, 24, 48 and 72 h or 1–3 weeks postirradiation. SAA levels were determined using a commercially available ELISA assay. Data was pooled to generate SAA μg/ml threshold values correlating plasma SAA levels with radiation dose. SAA levels were statistically significant over control at all exposures between 2 and 8 Gy at 24 h postirradiation but not at 6, 48 and 72 h or 1–3 weeks postirradiation. SAA levels at 1 Gy were not significantly elevated over control at all time points. Total-body-irradiated (TBI) SAA levels at 24 h were used to generate a dose prediction model that successfully differentiated TBI mice into dose received cohorts of control/1 Gy and ≥2 Gy groups with a high degree of accuracy in a blind study. Dose prediction of partial-body exposures based on the TBI model correlated increasing predictive accuracy with percentage of body exposure to radiation. Our findings indicate that plasma SAA levels might be a useful biomarker for radiation exposure in a variety of total- and partial-body irradiation settings. PMID:26114330

  5. Serum metabolomic profiles from patients with acute kidney injury: a pilot study.

    PubMed

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K; Khan, Nasim A; Portilla, Didier; Beger, Richard D

    2012-04-15

    Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients.

  6. Serum Metabolomic Profiles from Patients with Acute Kidney Injury: A Pilot Study

    PubMed Central

    Sun, Jinchun; Shannon, Melissa; Ando, Yosuke; Schnackenberg, Laura K.; Khan, Nasim A.; Portilla, Didier; Beger, Richard D

    2012-01-01

    Low sensitivity of current clinical markers (serum creatinine, blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AKI. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients. PMID:22429878

  7. Biomarkers and transcriptome profiling of lung cancer.

    PubMed

    Chen, Hsuan-Yu; Yu, Sung-Liang; Li, Ker-Chau; Yang, Pan-Chyr

    2012-05-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. High-throughput technologies such as microarrays provide an opportunity to explore biomarkers for cancer prevention, prognosis and treatment guidance. Recent studies have revealed many biomarkers with the potential for clinical application. However, major limitations still exist. Although useful data on cancer genomics has accumulated rapidly, there has also been a simultaneous tendency for amplification of the complex relationships among the enormous number of variables that need to be considered. Disentangling these complex gene-gene interactions requires new approaches to data analysis to reveal information that has been obscured by traditional methods. Here, we review the current findings on biomarker identification in lung cancer, address their limitations and discuss some future directions for improvements in this area of research.

  8. A novel profile biomarker diagnosis for mass spectral proteomics.

    PubMed

    Han, Henry

    2014-01-01

    Mass spectrometry based proteomics technologies have allowed for a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, they face acute challenges from a data reproducibility standpoint, in that no two independent studies have been found to produce the same proteomic patterns. Such reproducibility issues cause the identified biomarker patterns to lose repeatability and prevent real clinical usage. In this work, we propose a profile biomarker approach to overcome this problem from a machine-learning viewpoint by developing a novel derivative component analysis (DCA). As an implicit feature selection algorithm, derivative component analysis enables the separation of true signals from red herrings by capturing subtle data behaviors and removing system noises from a proteomic profile. We further demonstrate its advantages in disease diagnosis by viewing input data as a profile biomarker. The results from our profile biomarker diagnosis suggest an effective solution to overcoming proteomics data's reproducibility problem, present an alternative method for biomarker discovery in proteomics, and provide a good candidate for clinical proteomic diagnosis.

  9. A novel profile biomarker diagnosis for mass spectral proteomics.

    PubMed

    Han, Henry

    2014-01-01

    Mass spectrometry based proteomics technologies have allowed for a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, they face acute challenges from a data reproducibility standpoint, in that no two independent studies have been found to produce the same proteomic patterns. Such reproducibility issues cause the identified biomarker patterns to lose repeatability and prevent real clinical usage. In this work, we propose a profile biomarker approach to overcome this problem from a machine-learning viewpoint by developing a novel derivative component analysis (DCA). As an implicit feature selection algorithm, derivative component analysis enables the separation of true signals from red herrings by capturing subtle data behaviors and removing system noises from a proteomic profile. We further demonstrate its advantages in disease diagnosis by viewing input data as a profile biomarker. The results from our profile biomarker diagnosis suggest an effective solution to overcoming proteomics data's reproducibility problem, present an alternative method for biomarker discovery in proteomics, and provide a good candidate for clinical proteomic diagnosis. PMID:24297560

  10. Differentially Expressed RNA from Public Microarray Data Identifies Serum Protein Biomarkers for Cross-Organ Transplant Rejection and Other Conditions

    PubMed Central

    Chen, Rong; Sigdel, Tara K.; Li, Li; Kambham, Neeraja; Dudley, Joel T.; Hsieh, Szu-chuan; Klassen, R. Bryan; Chen, Amery; Caohuu, Tuyen; Morgan, Alexander A.; Valantine, Hannah A.; Khush, Kiran K.; Sarwal, Minnie M.; Butte, Atul J.

    2010-01-01

    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. PMID:20885780

  11. Serum proteomic profiles of depressive subtypes.

    PubMed

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

    2016-01-01

    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. PMID:27404283

  12. Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis

    PubMed Central

    Regev, Keren; Paul, Anu; Healy, Brian; von Glenn, Felipe; Diaz-Cruz, Camilo; Gholipour, Taha; Mazzola, Maria Antonietta; Raheja, Radhika; Nejad, Parham; Glanz, Bonnie I.; Kivisakk, Pia; Chitnis, Tanuja; Weiner, Howard L.

    2016-01-01

    Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p < 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p < 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum. Conclusions: Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS. Classification of evidence: This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS. PMID:27606352

  13. Comprehensive evaluation of serum microRNAs as biomarkers in multiple sclerosis

    PubMed Central

    Regev, Keren; Paul, Anu; Healy, Brian; von Glenn, Felipe; Diaz-Cruz, Camilo; Gholipour, Taha; Mazzola, Maria Antonietta; Raheja, Radhika; Nejad, Parham; Glanz, Bonnie I.; Kivisakk, Pia; Chitnis, Tanuja; Weiner, Howard L.

    2016-01-01

    Objective: To identify circulating microRNAs (miRNAs) linked to disease stage and disability in multiple sclerosis (MS). Methods: Sera from 296 participants including patients with MS, other neurologic diseases (Alzheimer disease and amyotrophic lateral sclerosis), and inflammatory diseases (rheumatoid arthritis and asthma) and healthy controls (HCs) were tested. miRNA profiles were determined using LNA (locked nucleic acid)-based quantitative PCR. Patients with MS were categorized according to disease stage and disability. In the discovery phase, 652 miRNAs were measured in sera from 26 patients with MS and 20 HCs. Following this, significant miRNAs (p < 0.05) from the discovery set were validated using quantitative PCR in 58 patients with MS, 30 HCs, and in 74 samples from other disease controls (Alzheimer disease, amyotrophic lateral sclerosis, asthma, and rheumatoid arthritis). Results: We validated 7 miRNAs that differentiate patients with MS from HCs (p < 0.05 in both the discovery and validation phase); miR-320a upregulation was the most significantly changing serum miRNA in patients with MS. We also identified 2 miRNAs linked to disease progression, with miR-27a-3p being the most significant. Ten miRNAs correlated with the Expanded Disability Status Scale of which miR.199a.5p had the strongest correlation with disability. Of the 15 unique miRNAs we identified in the different group comparisons, 12 have previously been reported to be associated with MS but not in serum. Conclusions: Our findings identify circulating serum miRNAs as potential biomarkers to diagnose and monitor disease status in MS. Classification of evidence: This study provides Class III evidence that circulating serum miRNAs can be used as biomarker for MS.

  14. Six Serum miRNAs Fail to Validate as Myotonic Dystrophy Type 1 Biomarkers

    PubMed Central

    Fernandez-Costa, Juan M.; Llamusi, Beatriz; Bargiela, Ariadna; Zulaica, Miren; Alvarez-Abril, M. Carmen; Perez-Alonso, Manuel; Lopez de Munain, Adolfo

    2016-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease caused by expansion of a CTG microsatellite in the 3’ untranslated region of the DMPK gene. Despite characteristic muscular, cardiac, and neuropsychological symptoms, CTG trinucleotide repeats are unstable both in the somatic and germinal lines, making the age of onset, clinical presentation, and disease severity very variable. A molecular biomarker to stratify patients and to follow disease progression is, thus, an unmet medical need. Looking for a novel biomarker, and given that specific miRNAs have been found to be misregulated in DM1 heart and muscle tissues, we profiled the expression of 175 known serum miRNAs in DM1 samples. The differences detected between patients and controls were less than 2.6 fold for all of them and a selection of six candidate miRNAs, miR-103, miR-107, miR-21, miR-29a, miR-30c, and miR-652 all failed to show consistent differences in serum expression in subsequent validation experiments. PMID:26919350

  15. Six Serum miRNAs Fail to Validate as Myotonic Dystrophy Type 1 Biomarkers.

    PubMed

    Fernandez-Costa, Juan M; Llamusi, Beatriz; Bargiela, Ariadna; Zulaica, Miren; Alvarez-Abril, M Carmen; Perez-Alonso, Manuel; Lopez de Munain, Adolfo; Lopez-Castel, Arturo; Artero, Ruben

    2016-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disease caused by expansion of a CTG microsatellite in the 3' untranslated region of the DMPK gene. Despite characteristic muscular, cardiac, and neuropsychological symptoms, CTG trinucleotide repeats are unstable both in the somatic and germinal lines, making the age of onset, clinical presentation, and disease severity very variable. A molecular biomarker to stratify patients and to follow disease progression is, thus, an unmet medical need. Looking for a novel biomarker, and given that specific miRNAs have been found to be misregulated in DM1 heart and muscle tissues, we profiled the expression of 175 known serum miRNAs in DM1 samples. The differences detected between patients and controls were less than 2.6 fold for all of them and a selection of six candidate miRNAs, miR-103, miR-107, miR-21, miR-29a, miR-30c, and miR-652 all failed to show consistent differences in serum expression in subsequent validation experiments. PMID:26919350

  16. Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen

    PubMed Central

    Blumenstein, Brent; Saad, Fred; Hotte, Sebastien; Chi, Kim N; Eigl, Bernhard; Gleave, Martin; Jacobs, Cindy

    2013-01-01

    Abstract Elevated levels of clusterin (CLU), a stress-induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second-generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second-line chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed while on or within 6 months of first-line docetaxel-based chemotherapy. Exploratory analyses evaluated serum CLU levels during custirsen treatment and correlative clinical effects on prostate-specific antigen (PSA) response, overall survival, and any relationship between serum CLU and PSA. Men with mCRPC were treated with mitoxantrone/prednisone/custirsen (MPC, n = 22) or docetaxel retreatment/prednisone/custirsen (DPC plus DPC-Assigned, n = 45) in an open-label, multicenter study. Subject-specific profiles of PSA and serum CLU levels during treatment were characterized using statistical modeling to compute subject-specific summary measures; these measures were analyzed for relationship to survival using proportional hazard regression. Estimated individual serum CLU response profiles were scored as below or at/above the median level for the population through 100 days postrandomization. Median survival was longer for subjects scoring below the median serum CLU level compared with subjects at/above the median level, respectively (MPC: 15.1 months vs. 6.2 months; DPC-Pooled: 17.0 months vs. 12.1 months). Lowered serum CLU levels during custirsen treatment when in combination with either chemotherapy regimen were predictive of longer survival in mCRPC. These results support further evaluation of serum CLU as a therapeutic biomarker. Aside from PSA, there are currently no other prognostic or predictive biomarkers that can be used to guide treatment response

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

    PubMed Central

    Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2016-01-01

    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

  18. Metallomic Biomarkers in Cerebrospinal fluid and Serum in patients with Parkinson’s disease in Indian population

    PubMed Central

    Sanyal, Jaya; Ahmed, Shiek S. S. J.; Ng, Hon Keung Tony; Naiya, Tufan; Ghosh, Epsita; Banerjee, Tapas Kumar; Lakshmi, Jaya; Guha, Gautam; Rao, Vadlamudi Raghavendra

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disease with the absence of markers for diagnosis. Several studies on PD reported the elements imbalance in biofluids as biomarkers. However, their results remained inconclusive. This study integrates metallomics, multivariate and artificial neural network (ANN) to understand element variations in CSF and serum of PD patients from the largest cohort of Indian population to solve the inconsistent results of previous studies. Also, this study is aimed to (1) ascertain a common element signature between CSF and serum. (2) Assess cross sectional element variation with clinical symptoms. (3) Develop ANN models for rapid diagnosis. A metallomic profile of 110 CSF and 530 serum samples showed significant variations in 10 elements of CSF and six in serum of patients compared to controls. Consistent variations in elements pattern were noticed for Calcium, Magnesium and Iron in both the fluids of PD, which provides feasible diagnosis from serum. Furthermore, implementing multivariate analyses showed clear classification between normal and PD in both the fluids. Also, ANN provides 99% accuracy in detection of disease from CSF and serum. Overall, our analyses demonstrate that elements profile in biofluids of PD will be useful in development of diagnostic markers for PD. PMID:27752066

  19. Inflammatory biomarker profiling in elderly patients with acute hip fracture treated with heparins.

    PubMed

    Knesek, Michael John; Litinas, Evangelos; Adiguzel, Cafer; Hopkinson, William; Hoppensteadt, Debra; Lassen, Michael; Fareed, Jawed

    2010-02-01

    Hip fracture is common in the elderly patients with associated high risk of venous thromboembolic complications. Pathogenic activation results in the generation of various surrogate markers in plasma. This study is designed to identify unique biomarkers in elderly patients with hip fracture using protein chip array enzyme-linked immunosorbent assay (ELISA) methods. Plasma from a randomized hip fracture study (PK-532; n = 341) treated with either enoxaparin (40 mg once daily) or unfractionated heparin (UFH; 5000 IU twice daily) were collected prior to and at 1, 3, 5, and 7 days. A total of 52 samples were analyzed using proteomic surface-enhanced laser desorption/ ionization-time of flight (SELDI-TOF) mass spectrometry to identify unique biomarkers in the molecular weight range of 0 to 150 kd. Twenty-nine healthy volunteer's and pooled plasma from total hip replacement/total knee replacement patients with a unique biomarker at 11.9 kd were used as quality controls. In the 29 healthy individuals, the biomarker profile did not reveal the presence of any unique peak in comparison to the reference normal human plasma (NHP). Plasma obtained prior to surgery exhibits unique biomarkers in 4 of 52 (7.6%) of the samples. On day 1 postoperatively, 41 of 51 (80.3%) showed a distinct peak at 11.9 kd. On day 3, 43 of 49 (87.8%) patients showed the presence of this biomarker most often at its strongest intensity. In all, 22 of 44 (50%) showed this biomarker on day 5 and 4 of 23 (17.9%) on day 7. C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and serum amyloid A were also increased after surgery. Tissue factor pathway inhibitor (TFPI) antigen levels were increased due to the treatment modalities.

  20. Serum Thiols as a Biomarker of Disease Activity in Lupus Nephritis

    PubMed Central

    Lalwani, Pritesh; de Souza, Giselle Katiane Bonfim Bacelar; de Lima, Domingos Savio Nunes; Passos, Luiz Fernando Souza; Boechat, Antonio Luiz; Lima, Emerson Silva

    2015-01-01

    Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol’s cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings. PMID:25799079

  1. A serum 6-miRNA panel as a novel non-invasive biomarker for meningioma

    PubMed Central

    Zhi, Feng; Shao, Naiyuan; Li, Bowen; Xue, Lian; Deng, Danni; Xu, Yuan; Lan, Qing; Peng, Ya; Yang, Yilin

    2016-01-01

    Circulating microRNAs (miRNAs) hold great promise as novel clinically blood-based biomarkers for cancer diagnosis and prognosis. However, little is known about their impact in meningioma. The TLDA assay was performed as an initial survey to determine the serum miRNA expression profile in two pooled samples from 20 pre-operative meningiomas and 20 matched healthy controls. Selected candidate miRNAs were subsequently validated individually in another 210 patients and 210 healthy controls from two independent cohorts by qRT-PCR. The serum levels of miR-106a-5p, miR-219-5p, miR-375, and miR-409-3p were significantly increased, whereas the serum levels of miR-197 and miR-224 were markedly decreased. The area under the ROC curve (AUC) for the six combined miRNAs was 0.778. The 4 increased miRNAs were significantly decreased, while the 2 decreased miRNAs were significantly increased after tumor removal. Furthermore, the expression levels of miR-224 were associated with sex, and the expression levels of miR-219-5p were positively associated with the clinical stages of meningioma. Finally, the high expression of miR-409-3p and low expression of miR-224 were significantly correlated with higher recurrence rates. The present study revealed that the panel of 6 serum miRNA may have the potential to be used clinically as an auxiliary tool for meningioma patients. PMID:27558167

  2. Evaluation of TKTL1 as a biomarker in serum of prostate cancer patients

    PubMed Central

    Thurn, Kristina; Juengel, Eva; Oppermann, Elsie; Nelson, Karen; Thomas, Christian; Bartsch, Georg; Oremek, Gerhard M.; Haferkamp, Axel; Rubenwolf, Peter; Blaheta, Roman A.

    2016-01-01

    Introduction Monocyte associated transketolase-like 1 (TKTL1) as a cancer biomarker has become popular with alternative practitioners, but plays no role in conventional medicine. This investigation evaluates the potential of serum TKTL1 as a biomarker for prostate cancer. Material and methods Patients (n = 66) undergoing curative radical prostatectomy (RPE) for biopsy-pro-ven PCa were included in the study. Controls (n = 10) were healthy, age-matched, male volunteers. 10 ml of peripheral blood was drawn from patients several days before surgery and from controls. Serum TKTL1 was measured using the ELISA method. Results The median age at tumor diagnosis was 66 years and median serum PSA was 8.0 ng/ml. Nearly 96% of PCas submitted to surgery were clinically significant. Compared to healthy controls, serum TKTL1 was significantly lower in PCa patients (p = 0.0001, effect size indicator r = Z/sqr(n) = 0.4179). No correlation was apparent between serum TKTL1 and serum PSA, Gleason sum, tumor stage or further clinical and pathologic parameters. Conclusions Reduced serum TKTL1 in PCa patients stands in opposition to TKTL1 epitope detection in monocytes (EDIM) based studies, whereby increased TKTL1 in monocytes of tumor patients has been reported. Since serum TKTL1 does not correlate with clinical parameters in the current investigation, further research is needed to clarify whether serum TKTL1 has potential as a biomarker for PCa. PMID:27729989

  3. Low Serum Fetuin-A as a Biomarker to Predict Pneumococcal Necrotizing Pneumonia and Hemolytic Uremic Syndrome in Children

    PubMed Central

    Janapatla, Rajendra Prasad; Hsu, Mei-Hua; Liao, Wan-Ting; Chien, Kun-Yi; Lee, Hao-Yuan; Chiu, Cheng-Hsun

    2016-01-01

    Abstract Streptococcus pneumoniae, a neuraminidase-producing pathogen, can cause invasive pneumococcal disease (IPD) with or without hemolytic uremic syndrome (HUS) in humans. We aimed to identify serum sialoglycoproteins that are targeted by neuraminidases in severe pneumococcal infection. We hypothesized that serum sialoglycoprotein such as fetuin-A can serve as a biomarker to predict IPD or HUS. We constructed serum sialoglycoprotein profiles before and after pneumococcal neuraminidase treatment using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a proteomic approach. An observational study was conducted using clinical data and serum samples from pediatric patients with pneumococcal infection to verify the predictive role of fetuin-A in IPD. Serum fetuin-A levels were determined by enzyme-linked immunosorbent assay. The most abundant serum sialoglycoproteins identified by LC-MS/MS after neuraminidase treatment and peanut lectin capture were immunoglobulins, apolipoproteins, fibrinogens, keratins, complement system proteins, and fetuin-A. Serum fetuin-A levels in the HUS patients were significantly lower (207 ± 80 mg/L, P < 0.001) than in patients with lobar pneumonia (610 ± 190 mg/L) as well as the healthy controls (630 ± 250 mg/L). In comparing HUS with necrotizing pneumonia and lobar pneumonia, the ROC area under the curve was 0.842; a cutoff value of 298 mg/L yielded sensitivity of 92.9% (95% CI: 68.5–98.7%) and specificity of 71.9% (95% CI: 54.6–84.4%). This observational study with validation cohorts of patients with HUS, complicated pneumonia, and lobar pneumonia demonstrates the high performance of low serum fetuin-A levels as a biomarker to predict severe IPD and HUS in children. PMID:27043691

  4. The role of serum biomarkers in the diagnosis and prognosis of oral cancer: A systematic review

    PubMed Central

    Fernández-Olavarría, Ana; Mosquera-Pérez, Regina; Díaz-Sánchez, Rosa-María; Serrera-Figallo, Maria-Angeles; Gutiérrez-Pérez, José-Luis

    2016-01-01

    Introduction Oral cancer is one of the causes of major morbidity and mortality in the world although incidence varies in the different geographical locations and races. Advances in molecular biology and cancer research have allowed elucidating serum biomarkers to improve diagnostic methods. The aim of this article systematic review is to highlight the utility and clinical value of serum biomarkers in the diagnosis and prognosis of oral cancer. Material and Methods A systematic literature review using PubMed (MEDLINE databases) revealed a total of 140 articles related to this topic. Of those articles, 29 were included in the final review. We included articles published in English in the last five years, developed in human as cases and controls studies, retrospective or prospective studies and specific studies that analyzed a certain biomarker in serum. Results All of the studies include in this systematic review found significant differences in patients. Of those articles included, 2 used biomarkers to determinate cancerous phenotype, 11 mentioned their results were associated with worse prognosis and overall survival, 4 correlated biomarker concentration to clinical stages, 4 concluded it could be a helpful in diagnosis and 8 studies did not find a clear utility of the analysed biomarker. Due to differences in the presentation of data, meta-analysis was not possible. Conclusions Biomarker use for diagnosis and prognosis is supported by clinical and scientific evidence is relevant. Nevertheless, after selecting a certain biomarker, monitoring protocols should be established in oral and maxillofacial surgeons teams so as we have a correct understanding of biological values. Key words:Serum biomarkers, oral cancer, diagnosis, prognosis. PMID:27034760

  5. Serum Antibody Repertoire Profiling Using In Silico Antigen Screen

    PubMed Central

    Liu, Xinyue; Hu, Qiang; Liu, Song; Tallo, Luke J.; Sadzewicz, Lisa; Schettine, Cassandra A.; Nikiforov, Mikhail; Klyushnenkova, Elena N.; Ionov, Yurij

    2013-01-01

    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. PMID:23826227

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

    PubMed

    Liu, Xinyue; Hu, Qiang; Liu, Song; Tallo, Luke J; Sadzewicz, Lisa; Schettine, Cassandra A; Nikiforov, Mikhail; Klyushnenkova, Elena N; Ionov, Yurij

    2013-01-01

    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. PMID:23826227

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

    PubMed Central

    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. PMID:26886592

  8. Analysis of gene expression profile identifies potential biomarkers for atherosclerosis.

    PubMed

    Liu, Luran; Liu, Yan; Liu, Chang; Zhang, Zhuobo; Du, Yaojun; Zhao, Hao

    2016-10-01

    The present study aimed to identify potential biomarkers for atherosclerosis via analysis of gene expression profiles. The microarray dataset no. GSE20129 was downloaded from the Gene Expression Omnibus database. A total of 118 samples from the peripheral blood of female patients was used, including 47 atherosclerotic and 71 non‑atherosclerotic patients. The differentially expressed genes (DEGs) in the atherosclerosis samples were identified using the Limma package. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery tool. The recursive feature elimination (RFE) algorithm was applied for feature selection via iterative classification, and support vector machine classifier was used for the validation of prediction accuracy. A total of 430 DEGs in the atherosclerosis samples were identified, including 149 up‑ and 281 downregulated genes. Subsequently, the RFE algorithm was used to identify 11 biomarkers, whose receiver operating characteristic curves had an area under curve of 0.92, indicating that the identified 11 biomarkers were representative. The present study indicated that APH1B, JAM3, FBLN2, CSAD and PSTPIP2 may have important roles in the progression of atherosclerosis in females and may be potential biomarkers for early diagnosis and prognosis as well as treatment targets for this disease. PMID:27573188

  9. Analysis of gene expression profile identifies potential biomarkers for atherosclerosis

    PubMed Central

    Liu, Luran; Liu, Yan; Liu, Chang; Zhang, Zhuobo; Du, Yaojun; Zhao, Hao

    2016-01-01

    The present study aimed to identify potential biomarkers for atherosclerosis via analysis of gene expression profiles. The microarray dataset no. GSE20129 was downloaded from the Gene Expression Omnibus database. A total of 118 samples from the peripheral blood of female patients was used, including 47 atherosclerotic and 71 non-atherosclerotic patients. The differentially expressed genes (DEGs) in the atherosclerosis samples were identified using the Limma package. Gene ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery tool. The recursive feature elimination (RFE) algorithm was applied for feature selection via iterative classification, and support vector machine classifier was used for the validation of prediction accuracy. A total of 430 DEGs in the atherosclerosis samples were identified, including 149 up- and 281 downregulated genes. Subsequently, the RFE algorithm was used to identify 11 biomarkers, whose receiver operating characteristic curves had an area under curve of 0.92, indicating that the identified 11 biomarkers were representative. The present study indicated that APH1B, JAM3, FBLN2, CSAD and PSTPIP2 may have important roles in the progression of atherosclerosis in females and may be potential biomarkers for early diagnosis and prognosis as well as treatment targets for this disease. PMID:27573188

  10. Identification of novel, therapy-responsive protein biomarkers in a mouse model of Duchenne muscular dystrophy by aptamer-based serum proteomics

    PubMed Central

    Coenen-Stass, Anna M. L.; McClorey, Graham; Manzano, Raquel; Betts, Corinne A.; Blain, Alison; Saleh, Amer F.; Gait, Michael J.; Lochmüller, Hanns; Wood, Matthew J. A.; Roberts, Thomas C.

    2015-01-01

    There is currently an urgent need for biomarkers that can be used to monitor the efficacy of experimental therapies for Duchenne Muscular Dystrophy (DMD) in clinical trials. Identification of novel protein biomarkers has been limited due to the massive complexity of the serum proteome and the presence of a small number of very highly abundant proteins. Here we have utilised an aptamer-based proteomics approach to profile 1,129 proteins in the serum of wild-type and mdx (dystrophin deficient) mice. The serum levels of 96 proteins were found to be significantly altered (P < 0.001, q < 0.01) in mdx mice. Additionally, systemic treatment with a peptide-antisense oligonucleotide conjugate designed to induce Dmd exon skipping and recover dystrophin protein expression caused many of the differentially abundant serum proteins to be restored towards wild-type levels. Results for five leading candidate protein biomarkers (Pgam1, Tnni3, Camk2b, Cycs and Adamts5) were validated by ELISA in the mouse samples. Furthermore, ADAMTS5 was found to be significantly elevated in human DMD patient serum. This study has identified multiple novel, therapy-responsive protein biomarkers in the serum of the mdx mouse with potential utility in DMD patients. PMID:26594036

  11. Searching for biomarkers: humoral response profiling with luciferase immunoprecipitation systems.

    PubMed

    Burbelo, Peter D; Ching, Kathryn H; Bren, Kathleen E; Iadarola, Michael J

    2011-06-01

    B-cell-mediated humoral responses are triggered in many human diseases, including autoimmune diseases, cancer, and neurologic and infectious diseases. However, the full exploitation of the information contained within a patient's antibody repertoire for diagnosis, monitoring and even disease prediction has been limited due to the poor diagnostic performance of many immunoassay formats. We have developed luciferase immunoprecipitation systems (LIPS) that harnesses light-emitting proteins to generate high-definition antibody profiles that are optimal for both diagnostics and biomarker discovery. Here, we describe the results and implications from a range of LIPS-antibody profiling studies performed in our laboratory. These include highly sensitive diagnostics for domestic and global pathogens, insights into infection-related diseases, discovery of new biomarkers for human diseases, subcategorization of symptoms and identification of pathogenic autoantibodies against self-proteins. These investigations highlight the types of humoral response profiles associated with different diseases, provide new information related to disease pathogenesis and offer a framework for incorporating LIPS antibody profiling into global health initiatives and disease monitoring. PMID:21679112

  12. Antibody microarray profiling of human prostate cancer sera: antibody screening and identification of potential biomarkers.

    PubMed

    Miller, Jeremy C; Zhou, Heping; Kwekel, Joshua; Cavallo, Robert; Burke, Jocelyn; Butler, E Brian; Teh, Bin S; Haab, Brian B

    2003-01-01

    We developed a practical strategy for serum protein profiling using antibody microarrays and applied the method to the identification of potential biomarkers in prostate cancer serum. Protein abundances from 33 prostate cancer and 20 control serum samples were compared to abundances from a common reference pool using a two-color fluorescence assay. Robotically spotted microarrays containing 184 unique antibodies were prepared on two different substrates: polyacrylamide based hydrogels on glass and poly-1-lysine coated glass with a photoreactive cross-linking layer. The hydrogel substrate yielded an average six-fold higher signal-to-noise ratio than the other substrate, and detection of protein binding was possible from a greater number of antibodies using the hydrogels. A statistical filter based on the correlation of data from "reverse-labeled" experiment sets accurately predicted the agreement between the microarray measurements and enzyme-linked immunosorbent assay measurements, showing that this parameter can serve to screen for antibodies that are functional on microarrays. Having defined a set of reliable microarray measurements, we identified five proteins (von Willebrand Factor, immunoglobulinM, Alpha1-antichymotrypsin, Villin and immunoglobulinG) that had significantly different levels between the prostate cancer samples and the controls. These developments enable the immediate use of high-density antibody and protein microarrays in biomarker discovery studies. PMID:12548634

  13. Reduction in serum clusterin is a potential therapeutic biomarker in patients with castration-resistant prostate cancer treated with custirsen.

    PubMed

    Blumenstein, Brent; Saad, Fred; Hotte, Sebastien; Chi, Kim N; Eigl, Bernhard; Gleave, Martin; Jacobs, Cindy

    2013-08-01

    Elevated levels of clusterin (CLU), a stress-induced and secreted cytoprotective chaperone, are associated with advanced tumor stage, metastasis, treatment resistance, and adverse outcome in several cancers. Custirsen, a second-generation antisense oligonucleotide, inhibits CLU production in tumor cells and reduces serum CLU levels. A Phase 2 study evaluated custirsen in combination with second-line chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC) who had progressed while on or within 6 months of first-line docetaxel-based chemotherapy. Exploratory analyses evaluated serum CLU levels during custirsen treatment and correlative clinical effects on prostate-specific antigen (PSA) response, overall survival, and any relationship between serum CLU and PSA. Men with mCRPC were treated with mitoxantrone/prednisone/custirsen (MPC, n = 22) or docetaxel retreatment/prednisone/custirsen (DPC plus DPC-Assigned, n = 45) in an open-label, multicenter study. Subject-specific profiles of PSA and serum CLU levels during treatment were characterized using statistical modeling to compute subject-specific summary measures; these measures were analyzed for relationship to survival using proportional hazard regression. Estimated individual serum CLU response profiles were scored as below or at/above the median level for the population through 100 days postrandomization. Median survival was longer for subjects scoring below the median serum CLU level compared with subjects at/above the median level, respectively (MPC: 15.1 months vs. 6.2 months; DPC-Pooled: 17.0 months vs. 12.1 months). Lowered serum CLU levels during custirsen treatment when in combination with either chemotherapy regimen were predictive of longer survival in mCRPC. These results support further evaluation of serum CLU as a therapeutic biomarker.

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

    NASA Astrophysics Data System (ADS)

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

    PubMed

    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). PMID:25362477

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

    PubMed

    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).

  17. Serum Proteome Profiling Identifies Novel and Powerful Markers of Cystic Fibrosis Liver Disease

    PubMed Central

    Kügler, Marion; Menendez Menendez, Katrin; Zachoval, Reinhart; Naehrlich, Lutz; Schulz, Richard; Roderfeld, Martin; Roeb, Elke

    2013-01-01

    Background and Aims Cystic Fibrosis associated liver disease (CFLD) develops in approximately 30% of CF patients. However, routine sensitive diagnostic tools for CFLD are lacking. Within this study, we aimed to identify new experimental biomarkers for the detection of CFLD. Methods 45 CF patients were included in the study and received transient elastography. Differential regulation of 220 different serum proteins was assessed in a subgroup of patients with and without CFLD. Most interesting candidate proteins were further quantified and validated by ELISA in the whole patient cohort. To assess a potential relation of biomarker expression to the degree of hepatic fibrosis, serum biomarkers were further determined in 18 HCV patients where liver histology was available. Results 43 serum proteins differed at least 2-fold in patients with CFLD compared to those without liver disease as identified in proteome profiling. In ELISA quantifications, TIMP-4 and Endoglin were significantly up-regulated in patients with CFLD as diagnosed by clinical guidelines or increased liver stiffness. Pentraxin-3 was significantly decreased in patients with CFLD. Serum TIMP-4 and Endoglin showed highest values in HCV patients with liver cirrhosis compared to those with fibrosis but without cirrhosis. At a cut-off value of 6.3 kPa, transient elastography compassed a very high diagnostic accuracy and specificity for the detection of CFLD. Among the biomarkers, TIMP-4 and Endoglin exhibited a high diagnostic accuracy for CFLD. Diagnostic sensitivities and negative predictive values were increased when elastography and TIMP-4 and Endoglin were combined for the detection of CFLD. Conclusions Serum TIMP-4 and Endoglin are increased in CFLD and their expression correlates with hepatic staging. Determination of TIMP-4 and Endoglin together with transient elastography can increase the sensitivity for the non-invasive diagnosis of CFLD. PMID:23516586

  18. The multiplex bead array approach to identifying serum biomarkers associated with breast cancer

    PubMed Central

    Kim, Byoung Kwon; Lee, Jong Won; Park, Pil Je; Shin, Yong Sung; Lee, Won Young; Lee, Kyung Ae; Ye, Sena; Hyun, Heesun; Kang, Kyung Nam; Yeo, Donghwa; Kim, Youngdai; Ohn, Sung Yup; Noh, Dong Young; Kim, Chul Woo

    2009-01-01

    Introduction Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Methods Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex™ bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Results Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater

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

    PubMed

    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 and Urine Biomarkers for Human Renal Cell Carcinoma

    PubMed Central

    Pastore, A. L.; Palleschi, G.; Silvestri, L.; Moschese, D.; Ricci, S.; Petrozza, V.; Carbone, A.; Di Carlo, A.

    2015-01-01

    Renal cell carcinoma (RCC) diagnosis is mostly achieved incidentally by imaging provided for unrelated clinical reasons. The surgical management of localized tumors has reported excellent results. The therapy of advanced RCC has evolved considerably over recent years with the widespread use of the so-called “targeted therapies.” The identification of molecular markers in body fluids (e.g., sera and urine), which can be used for screening, diagnosis, follow-up, and monitoring of drug-based therapy in RCC patients, is one of the most ambitious challenges in oncologic research. Although there are some promising reports about potential biomarkers in sera, there is limited available data regarding urine markers for RCC. The following review reports some of the most promising biomarkers identified in the biological fluids of RCC patients. PMID:25922552

  1. Serum miRNA expression profiles change in autoimmune vitiligo in mice.

    PubMed

    Shi, Yu-Ling; Weiland, Matthew; Lim, Henry W; Mi, Qing-Sheng; Zhou, Li

    2014-02-01

    It is widely believed that non-segmental vitiligo results from the autoimmune destruction of melanocytes. MicroRNAs (miRNAs), a class of small non-coding RNAs that negatively regulate gene expression, are involved in the immune cell development and function and regulate the development of autoimmune diseases. Recent studies demonstrate that functional miRNAs can be detected in the serum and serve as biomarkers of various diseases. In the present study, we used a mouse autoimmune vitiligo model, in which melanocyte autoreactive CD4+ T cells were adoptively transferred into Rag1(-/-) host mice. Serum miRNA expression was profiled in vitiligo developed mice and control mice using TaqMan RT-PCR arrays. We have found that the expressions of 20 serum miRNAs were changed in vitiligo mice compared to control mice. Three increased miRNAs, miR-146a, miR-191, and miR-342-3p, were further confirmed by a single TaqMan RT-PCR. Our findings suggest that miRNAs may be involved in vitiligo development and serum miRNAs could serve as serum biomarkers for vitiligo in mice.

  2. Serum calprotectin: a new potential biomarker for thyroid papillary carcinoma.

    PubMed

    Tabur, S; Korkmaz, H; Özkaya, M; Elboğa, U; Tarakçıoglu, M; Aksoy, N; Akarsu, E

    2015-09-01

    The aim of this study was to evaluate serum calprotectin levels and oxidative stress status in patients with papillary thyroid carcinoma (PTC) and the changes in their levels after total thyroidectomy. The study involved 30 patients with PTC and 30 healthy controls. Blood samples were obtained from the PTC patients before and 1 month after the operation. Preoperative and postoperative serum samples from PTC patients and healthy controls were analysed for calprotectin, total antioxidant status (TAS), total oxidant status (TOS) and lipid hydroperokside (LOOH). The preoperative calprotectin, TOS, OSI and LOOH levels of the patients with PTC were significantly higher compared to those of the control group (p < 0.001, for each). The levels of calprotectin decreased significantly in patients with PTC after the operation (p < 0.001), while TAS, TOS and OSI levels remained unchanged (p = 0.313, p = 0.085 and p = 0.163, respectively). Preoperative serum calprotectin levels were positively correlated with TOS, OSI and LOOH levels and negatively correlated with TAS levels in patients with PTC. In conclusion, serum calprotectin levels is increased in patients with PTC, and calprotectin is positively correlated with TOS and LOOH. Serum calprotectin levels is significantly decreased after total thyroidectomy.

  3. A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection

    PubMed Central

    Dumstrei, Karin; Chen, Hongda; Brenner, Hermann

    2016-01-01

    Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in detecting it at early stages. While different markers have been associated with pancreatic cancer, many of them show suboptimal sensitivity and specificity. Serum autoantibodies against tumor-associated antigens have recently emerged as early stage biomarkers for different types of cancers. Given the urgent need for early and reliable biomarkers for pancreatic cancer, we undertook a systematic review of the published literature to identify primary articles that evaluated serum autoantibodies in pancreatic cancer detection by searching PubMed and ISI Web of Knowledge. Two reviewers extracted data on study characteristics and results independently. Overall, 31 studies evaluating 124 individual serum autoantibodies in pancreatic cancer detection met the inclusion criteria. In general, single autoantibody markers showed relatively low sensitivities at high specificity. A combination of markers, either multiple serum autoantibodies or serum autoantibodies combined with tumor-associated markers, led to a better diagnostic performance. However, most of the analyzed autoantibodies have only been reported in single studies and therefore need to be independently validated. We conclude that serum autoantibodies might present an option as biomarkers for early detection of pancreatic cancer, but more work is needed to identify and validate autoantibody signatures that are associated with early stage pancreatic cancer. PMID:26840568

  4. Utilization of Metabolomics to Identify Serum Biomarkers for Hepatocellular Carcinoma in Patients with Liver Cirrhosis

    PubMed Central

    Ressom, Habtom W.; Xiao, Jun Feng; Tuli, Leepika; Varghese, Rency S.; Zhou, Bin; Tsai, Tsung-Heng; Nezami Ranjbar, Mohammad R.; Zhao, Yi; Wang, Jinlian; Di Poto, Cristina; Cheema, Amrita K.; Tadesse, Mahlet G.; Goldman, Radoslav; Shetty, Kirti

    2012-01-01

    Characterizing the metabolic changes pertaining to hepatocellular carcinoma (HCC) in patients with liver cirrhosis is believed to contribute towards early detection, treatment, and understanding of the molecular mechanisms of HCC. In this study, we compare metabolite levels in sera of 78 HCC cases with 184 cirrhotic controls by using ultra performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from patients with cirrhosis are selected by parametric and non-parametric statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. Verification of the identities of selected metabolites is conducted by comparing their MS/MS fragmentation patterns and retention time with those from authentic compounds. Quantitation of these metabolites is performed in a subset of the serum samples (10 HCC and 10 cirrhosis) using isotope dilution by selected reaction monitoring (SRM) on triple quadrupole linear ion trap (QqQLIT) and triple quadrupole (QqQ) mass spectrometers. The results of this analysis confirm that metabolites involved in sphingolipid metabolism and phospholipid catabolism such as sphingosine-1-phosphate (S-1-P) and lysophosphatidylcholine (lysoPC 17:0) are up-regulated in sera of HCC vs. those with liver cirrhosis. Down-regulated metabolites include those involved in bile acid biosynthesis (specifically cholesterol metabolism) such as glycochenodeoxycholic acid 3-sulfate (3-sulfo-GCDCA), glycocholic acid (GCA), glycodeoxycholic acid (GDCA), taurocholic acid (TCA), and taurochenodeoxycholate (TCDCA). These results provide useful insights into HCC biomarker discovery utilizing metabolomics as an efficient and cost-effective platform. Our work shows that metabolomic profiling is a promising tool to identify candidate metabolic biomarkers for early detection of HCC cases in

  5. Serum CA 19-9 as a Biomarker for Pancreatic Cancer-A Comprehensive Review.

    PubMed

    Ballehaninna, Umashankar K; Chamberlain, Ronald S

    2011-06-01

    Pancreatic cancer is an aggressive tumor with a dismal prognosis, biomarkers that can detect tumor in its early stages when it may be amenable to curative resection may improve prognosis. At present, serum CA 19-9 is the only validated tumor marker in widespread clinical use, but precise knowledge of its role in pancreatic cancer diagnosis, staging, determining resectability, response to chemotherapy and prognosis remains limited. A comprehensive search was performed using PubMed with keywords "pancreatic cancer" "tumor markers" "CA 19-9" "diagnosis" "screening" "prognosis" "resectability" and "recurrence". All English language articles pertaining to the role of CA 19-9 in pancreatic cancer were critically analyzed to determine its utility as a biomarker for pancreatic cancer. Serum CA 19-9 is the most extensively studied and clinically useful biomarker for pancreatic cancer. Unfortunately, CA 19-9 serum level evaluation in pancreatic cancer patients is limited by poor sensitivity, false negative results in Lewis negative phenotype (5-10%) and increased false positivity in the presence of obstructive jaundice (10-60%). Serum CA 19-9 level has no role in screening asymptomatic populations, and has a sensitivity and specificity of 79-81% and 82-90% respectively for the diagnosis of pancreatic cancer in symptomatic patients. Pre-operative CA 19-9 serum level provide useful prognostic information as patients with normal CA 19-9 serum levels (<37 U/ml) have a prolonged median survival (32-36 months) compared to patients with elevated CA 19-9 serum levels (>37 U/ml) (12-15 months). A CA 19-9 serum level of <100 U/ml implies likely resectable disease whereas levels >100 U/ml may suggest unresectablity or metastatic disease. Normalization or a decrease in post-operative CA 19-9 serum levels by ≥20-50% from baseline following surgical resection or chemotherapy is associated with prolonged survival compared to failure of CA 19-9 serum levels to normalize or an

  6. Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer?

    PubMed Central

    Margue, Christiane; Beaume, Nicolas; Walters, Casandra; Schneider, Jochen G.; Nashan, Dorothée; Behrmann, Iris; Kreis, Stephanie

    2015-01-01

    MiRNAs are increasingly recognized as biomarkers for the diagnosis of cancers where they are profiled from tumor tissue (intracellular miRNAs) or serum/plasma samples (extracellular miRNAs). To improve detection of reliable biomarkers from blood samples, we first compiled a healthy reference miRNome and established a well-controlled analysis pipeline allowing for standardized quantification of circulating miRNAs. Using whole miRNome and custom qPCR arrays, miRNA expression profiles were analyzed in 126 serum, whole blood and tissue samples of healthy volunteers and melanoma patients and in primary melanocyte and keratinocyte cell lines. We found characteristic signatures with excellent prognostic scores only in late stage but not in early stage melanoma patients. Upon comparison of melanoma tissue miRNomes with matching serum samples, several miRNAs were identified to be exclusively tissue-derived (miR-30b-5p, miR-374a-5p and others) while others had higher expression levels in serum (miR-3201 and miR-122-5p). Here we have compiled a healthy and widely applicable miRNome from serum samples and we provide strong evidence that levels of cell-free miRNAs only change significantly at later stages of melanoma progression, which has serious implications for miRNA biomarker studies in cancer. PMID:25883223

  7. Serum biomarkers in young adult and aged Brown Norway (BN) rats following episodic (weekly) ozone exposure

    EPA Science Inventory

    Ozone (03) is an air pollutant that is associated with cardiovascular and respiratory diseases. Older adults are considered to be particularly susceptible to oxidant air pollutants such as 03. Serum biomarkers are being sought that would lead to better predictions of susceptibili...

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

    PubMed Central

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

    2016-01-01

    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. PMID:27240929

  9. Clinical utility of serum biomarkers in Duchenne muscular dystrophy.

    PubMed

    Hathout, Yetrib; Seol, Haeri; Han, Meng Hsuan J; Zhang, Aiping; Brown, Kristy J; Hoffman, Eric P

    2016-01-01

    Assessments of disease progression and response to therapies in Duchenne muscular dystrophy (DMD) patients remain challenging. Current DMD patient assessments include complex physical tests and invasive procedures such as muscle biopsies, which are not suitable for young children. Defining alternative, less invasive and objective outcome measures to assess disease progression and response to therapy will aid drug development and clinical trials in DMD. In this review we highlight advances in development of non-invasive blood circulating biomarkers as a means to assess disease progression and response to therapies in DMD.

  10. Correlation analysis between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis

    PubMed Central

    TANG, NING; ZHANG, YAPING; LIU, ZEYU; FU, TAO; LIANG, QINGHONG; AI, XUEMEI

    2016-01-01

    The aim of the present study was to investigate the correlation between four serum biomarkers of liver fibrosis and liver function in infants with cholestasis. A total of 30 infants with cholestasis and 20 healthy infants were included in the study. Biochemical assays based on the initial rate method and colorimetric assays were conducted to determine the levels of liver function markers in the serum [such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), γ-glutamyl transferase (γ-GT), cholinesterase (CHE) and total bile acids (TBA)] and four serum biomarkers of liver fibrosis were measured using radioimmunoassays [hyaluronic acid (HA), procollagen type III (PCIII), laminin (LN) and collagen type IV (cIV)]. The serum levels of ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01); the serum levels of CHE in the infants with cholestasis were significantly lower compared to the healthy infants (P<0.01). The serum levels of HA, PCIII, and cIV in the infants with cholestasis were significantly higher compared to the healthy infants (P<0.01). Correlation analyses between liver function and the four biomarkers of liver fibrosis showed that HA was positively correlated with AST and γ-GT (P<0.05) and negatively correlated with ALT, CHE and TBA (P<0.05). cIV was positively correlated with γ-GT (P<0.05) and negatively correlated with CHE (P<0.05). In conclusion, statistically significant differences were identified for the liver function markers (ALT, AST, TBIL, DBIL, IBIL, γ-GT and TBA) and the biomarkers HA, PCIII and cIV of liver fibrosis between infants with cholestasis and healthy infants. Thus, the serum levels of HA, cIV, γ-GT and CHE are sensitive markers for cholestatic liver fibrosis in infants. PMID:27347413

  11. Schizopsychotic symptom-profiles and biomarkers: beacons in diagnostic labyrinths.

    PubMed

    Palomo, Tomas; Kostrzewa, Richard M; Beninger, Richard J; Archer, Trevor

    2008-10-01

    Several avenues of investigation through which the 'labyrinths' of schizopsychotic diagnosis may be examined, are offered by the consideration of the 'beacons' of symptom-profiles and biomarkers. Neurodevelopmental issues and risk assessment, neurocognitive factors of predictive necessity, supersensitivity in neurotransmitter systems, the implications of prodromal expressions of the disorder, functional dysconnectivity arising from prefrontal to diverse regional patterns and circuits with a neurodevelopmental origin, and heritable gene characteristics are viewed against the backdrop of the schizophrenia spectrum disorders. The associations between adolescent-adult use of cannabis, on the one hand, and, alternatively, the prevalence of chromosomal abnormalities, e.g., GRIK4 and NPAS3, and mental retardation, on the other hand, with the symptom-profiles of schizopsychosis provide further evidence of emerging biomarkers of biological inheritance factors. The involvement of dopamine D1 and D2 receptors, particularly in prefrontal region, with regard to functional integrity of cognitive systems is reviewed. It would appear that considerations of these disorders imply that one essential hub around which much of the neuropathology revolves may be observed in the various expressions of the cognitive and structural insufficiency.

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

    PubMed Central

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

    2014-01-01

    Background: 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. Objectives: 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. Materials and Methods: 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. Results: Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content. Conclusions: Cornus 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. PMID:24829584

  13. Distinctive serum miRNA profile in mouse models of striated muscular pathologies.

    PubMed

    Vignier, Nicolas; Amor, Fatima; Fogel, Paul; Duvallet, Angélique; Poupiot, Jérôme; Charrier, Sabine; Arock, Michel; Montus, Marie; Nelson, Isabelle; Richard, Isabelle; Carrier, Lucie; Servais, Laurent; Voit, Thomas; Bonne, Gisèle; Israeli, David

    2013-01-01

    Biomarkers are critically important for disease diagnosis and monitoring. In particular, close monitoring of disease evolution is eminently required for the evaluation of therapeutic treatments. Classical monitoring methods in muscular dystrophies are largely based on histological and molecular analyses of muscle biopsies. Such biopsies are invasive and therefore difficult to obtain. The serum protein creatine kinase is a useful biomarker, which is however not specific for a given pathology and correlates poorly with the severity or course of the muscular pathology. The aim of the present study was the systematic evaluation of serum microRNAs (miRNAs) as biomarkers in striated muscle pathologies. Mouse models for five striated muscle pathologies were investigated: Duchenne muscular dystrophy (DMD), limb-girdle muscular dystrophy type 2D (LGMD2D), limb-girdle muscular dystrophy type 2C (LGMD2C), Emery-Dreifuss muscular dystrophy (EDMD) and hypertrophic cardiomyopathy (HCM). Two-step RT-qPCR methodology was elaborated, using two different RT-qPCR miRNA quantification technologies. We identified miRNA modulation in the serum of all the five mouse models. The most highly dysregulated serum miRNAs were found to be commonly upregulated in DMD, LGMD2D and LGMD2C mouse models, which all exhibit massive destruction of striated muscle tissues. Some of these miRNAs were down rather than upregulated in the EDMD mice, a model without massive myofiber destruction. The dysregulated miRNAs identified in the HCM model were different, with the exception of one dysregulated miRNA common to all pathologies. Importantly, a specific and distinctive circulating miRNA profile was identified for each studied pathological mouse model. The differential expression of a few dysregulated miRNAs in the DMD mice was further evaluated in DMD patients, providing new candidates of circulating miRNA biomarkers for DMD.

  14. Proteomic profiling in the sera of workers occupationally exposed to arsenic and lead: identification of potential biomarkers.

    PubMed

    Zhai, Rihong; Su, Suhua; Lu, Xin; Liao, Ruiqing; Ge, Xianmin; He, Min; Huang, Yuanjiao; Mai, Sui; Lu, Xi; Christiani, David

    2005-12-01

    Arsenic (As) and lead (Pb) are important inorganic toxicants in the environment. Frequently, humans are exposed to the mixtures of As and Pb, but little is known about the expression of biomarkers resulting from such mixed exposures. In this study, we analyzed serum proteomic profiles in a group of smelter workers with the aim of identifying protein biomarkers of mixed As and Pb exposure. Forty-six male workers co-exposed to As and Pb were studied. Forty-five age-matched male office workers were chosen as controls. Urine As and blood Pb concentrations were determined. Serum proteomic profiles were analyzed by Surface-Enhanced Laser Desorption/Ionization Time-Of-Flight (SELDI-TOF) mass spectrometer on the WCX2 ProteinChip. Using Recursive support vector machine (RSVM) algorithm, a panel of five peptides/proteins (2097 Da, 2953 Da, 3941 Da, 5338 Da, and 5639 Da) was selected based on their collective contribution to the optional separation between higher metal mixture exposure and non-exposure controls. Among these five selected markers, the 3941 Da was down-regulated and the four other proteins were up-regulated. Descriptive statistics confirmed that these five proteins differed significantly between metal exposure and non-exposure. Interestingly, the combined use of the five selected biomarkers could achieve higher discriminative power than single marker. These results demonstrated that proteomic technology, in conjunction with bioinformatics tools, could facilitate the discovery of new and better biomarkers of mixed metal exposure.

  15. Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity.

    PubMed

    Starling, Ana Lúcia Borges; Coelho-Dos-Reis, Jordana Grazziela Alves; Peruhype-Magalhães, Vanessa; Pascoal-Xavier, Marcelo Antônio; Gonçalves, Denise Utsch; Béla, Samantha Ribeiro; Lambertucci, José Roberto; Labanca, Ludimila; Souza Pereira, Silvio Roberto; Teixeira-Carvalho, Andréa; Ribas, João Gabriel; Trindade, Bruno Caetano; Faccioli, Lucia Helena; Carneiro-Proietti, Anna Bárbara Freitas; Martins-Filho, Olindo Assis

    2015-01-01

    This study aimed at establishing the immunological signature and an algorithm for clinical management of the different clinical stages of the HTLV-1-infection based on serum biomarkers. A panel of serum biomarkers was evaluated by four sets of innovative/non-conventional data analysis approaches in samples from 87 HTLV-1 patients: asymptomatic carriers (AC), putative HTLV-1 associated myelopathy/tropical spastic paraparesis (pHAM/TSP) and HAM/TSP. The analysis of cumulative curves and molecular signatures pointed out that HAM/TSP presented a pro-inflammatory profile mediated by CXCL10/LTB-4/IL-6/TNF-α/IFN-γ, counterbalanced by IL-4/IL-10. The analysis of biomarker networks showed that AC presented a strongly intertwined pro-inflammatory/regulatory net with IL-4/IL-10 playing a central role, while HAM/TSP exhibited overall immune response toward a predominant pro-inflammatory profile. At last, the classification and regression trees proposed for clinical practice allowed for the construction of an algorithm to discriminate AC, pHAM and HAM/TSP patients with the elected biomarkers: IFN-γ, TNF-α, IL-10, IL-6, IL-4 and CysLT. These findings reveal a complex interaction among chemokine/leukotriene/cytokine in HTLV-1 infection and suggest the use of the selected but combined biomarkers for the follow-up/diagnosis of disease morbidity of HTLV-1-infected individuals.

  16. Reliability of human serum protein profiles generated with C8 magnetic beads assisted MALDI-TOF mass spectrometry.

    PubMed

    de Noo, Mirre E; Tollenaar, Rob A E M; Ozalp, Aliye; Kuppen, Peter J K; Bladergroen, Marco R; Eilers, Paul H C; Deelder, André M

    2005-11-15

    Protein profiling with mass spectrometry is a promising approach for classification and identification of biomarkers; however, there is debate about measurement quality and reliability. Here, we present a pipeline for preprocessing, statistical data analysis and presentation. Serum samples of 16 healthy individuals are used to generate protein profiles with high-resolution MALDI-TOF after isolation of peptides with C8 magnetic beads. Analysis of variance was performed after binning, baseline correction and normalization of the mean spectra. Relative variations in the spectra are expressed as coefficient of variation, which depending on the respective preanalytical variation parameter investigated, was found to range between 0.15 and 0.67 in this study. With this novel method, the reproducibility of our protein profiling procedure could be quantified. We showed that circadian rhythm and the number of freeze-thaw cycles had relatively limited influence on serum protein profiles, whereas the period between collection and serum centrifugation had a more pronounced effect.

  17. The Value of Serum Biomarkers (Bc1, Bc2, Bc3) in the Diagnosis of Early Breast Cancer

    PubMed Central

    Atahan, Kemal; Küpeli, Hakan; Gür, Serhat; Yiğitbaşı, Türkan; Baskın, Yasemin; Yiğit, Seyran; Deniz, Mehmet; Çökmez, Atilla; Tarcan, Ercüment

    2011-01-01

    Background: Surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF) is an approach to biomarker discovery that combines chromatography and mass spectrometry. We aimed to consider the efficacy of Bc1, Bc2, and Bc3 serum biomarkers on early detection of breast cancer (BC) in this study. Study Design: In this prospective study, 91 patients who were admitted to our hospital between January 2007 and July 2008 were included. Serum samples from 91 women were stored at -80 °C until use. The cancer group included 27 cases of BC. The benign breast disease group included 24 women with benign breast diseases and control group 37 age-matched apparently healthy women. The data obtained for these three groups of patients was worked out for each serum biomarker (Bc1, Bc2, and Bc3) by using SELDI-TOF individually and compared with each other separately and evaluated statistically. Results: Bc2 possesses the highest individual diagnostic power. Bc2 was statistically significant in comparison between the malignant disease group, control group and benign disease group. Bc1 was statistically significant in the malignant disease group compared to control group as well as in the benign disease group compared to control group. Thus Bc1, rather than showing malignant progression, it shows tumoral progression or inflammatory process. Bc3 was found upregulated in all malignant cases; however, it was not statistically significant compared to the benign disease group or the control group. Conclusions: It has been shown that Bc2 profiles might be useful in clinical practice to improve BC diagnosis. However none of the proteomics reach reasonable AUC values for the discrimination of the BC. Additional confirmation in larger and similarly-designed prospective studies is needed to consider of the efficacy of Bc1 and Bc2 in early diagnosis of the BC. PMID:21326957

  18. Downregulated serum miR-223 servers as biomarker in Alzheimer's disease.

    PubMed

    Jia, Li-Hua; Liu, Yi-Ning

    2016-06-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder that is characterized by progressive memory loss and deteriorated higher cognitive functions. An economical, rapid and noninvasive biomarker for AD has not been identified. We aimed to investigate the diagnostic value of serum miR-223 and miR-519 in AD. The expressions of miR-223 and miR-519, with previously reported AD-associated miR-29 and miR-125b, were measured by quantitative reverse transcription polymerase chain reaction in the serum of 84 probable sporadic AD patients (age onset > 65 years) and 62 healthy control populations in China. Analyses were undertaken to assess the specificity and sensitivity of miRNAs to predict AD. In addition, the relationship between miRNAs and mini mental state examination (MMSE) scores in AD patients was also assessed. Serum miR-29, miR-125b and miR-223 were significantly decreased, but serum miR-519 was significantly increased in AD patients compared with healthy blood donors. In addition, serum miR-223 was strongly positively correlated with MMSE score in AD patients but serum miR-519 was not. Importantly, the receiver operating characteristic (ROC) result of serum miR-223 for prediction of AD was 0.786, higher than those of serum miR-29 (0.734) or miR-125b (0.726). The combination of serum miR-223 and miR-125b gave improved sensitivity/specificity for AD prediction (area under the ROC curve, 0.879) than either miRNA alone. Our preliminary findings indicate that serum miR-223 might be a potential biomarker for AD evaluation. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27027823

  19. Serum uPAR as Biomarker in Breast Cancer Recurrence: A Mathematical Model

    PubMed Central

    Hao, Wenrui; Friedman, Avner

    2016-01-01

    There are currently over 2.5 million breast cancer survivors in the United States and, according to the American Cancer Society, 10 to 20 percent of these women will develop recurrent breast cancer. Early detection of recurrence can avoid unnecessary radical treatment. However, self-examination or mammography screening may not discover a recurring cancer if the number of surviving cancer cells is small, while biopsy is too invasive and cannot be frequently repeated. It is therefore important to identify non-invasive biomarkers that can detect early recurrence. The present paper develops a mathematical model of cancer recurrence. The model, based on a system of partial differential equations, focuses on tissue biomarkers that include the plasminogen system. Among them, only uPAR is known to have significant correlation to its concentration in serum and could therefore be a good candidate for serum biomarker. The model includes uPAR and other associated cytokines and cells. It is assumed that the residual cancer cells that survived primary cancer therapy are concentrated in the same location within a region with a very small diameter. Model simulations establish a quantitative relation between the diameter of the growing cancer and the total uPAR mass in the cancer. This relation is used to identify uPAR as a potential serum biomarker for breast cancer recurrence. PMID:27078836

  20. Serum uPAR as Biomarker in Breast Cancer Recurrence: A Mathematical Model.

    PubMed

    Hao, Wenrui; Friedman, Avner

    2016-01-01

    There are currently over 2.5 million breast cancer survivors in the United States and, according to the American Cancer Society, 10 to 20 percent of these women will develop recurrent breast cancer. Early detection of recurrence can avoid unnecessary radical treatment. However, self-examination or mammography screening may not discover a recurring cancer if the number of surviving cancer cells is small, while biopsy is too invasive and cannot be frequently repeated. It is therefore important to identify non-invasive biomarkers that can detect early recurrence. The present paper develops a mathematical model of cancer recurrence. The model, based on a system of partial differential equations, focuses on tissue biomarkers that include the plasminogen system. Among them, only uPAR is known to have significant correlation to its concentration in serum and could therefore be a good candidate for serum biomarker. The model includes uPAR and other associated cytokines and cells. It is assumed that the residual cancer cells that survived primary cancer therapy are concentrated in the same location within a region with a very small diameter. Model simulations establish a quantitative relation between the diameter of the growing cancer and the total uPAR mass in the cancer. This relation is used to identify uPAR as a potential serum biomarker for breast cancer recurrence.

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

    PubMed Central

    2012-01-01

    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 < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05). Conclusions In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival. PMID:22906131

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

    PubMed Central

    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

  3. Targeted Lipid Profiling Discovers Plasma Biomarkers of Acute Brain Injury

    PubMed Central

    Sheth, Sunil A.; Iavarone, Anthony T.; Liebeskind, David S.; Won, Seok Joon; Swanson, Raymond A.

    2015-01-01

    Prior efforts to identify a blood biomarker of brain injury have relied almost exclusively on proteins; however their low levels at early time points and poor correlation with injury severity have been limiting. Lipids, on the other hand, are the most abundant molecules in the brain and readily cross the blood-brain barrier. We previously showed that certain sphingolipid (SL) species are highly specific to the brain. Here we examined the feasibility of using SLs as biomarkers for acute brain injury. A rat model of traumatic brain injury (TBI) and a mouse model of stroke were used to identify candidate SL species though our mass-spectrometry based lipid profiling approach. Plasma samples collected after TBI in the rat showed large increases in many circulating SLs following injury, and larger lesions produced proportionately larger increases. Plasma samples collected 24 hours after stroke in mice similarly revealed a large increase in many SLs. We constructed an SL score (sum of the two SL species showing the largest relative increases in the mouse stroke model) and then evaluated the diagnostic value of this score on a small sample of patients (n = 14) who presented with acute stroke symptoms. Patients with true stroke had significantly higher SL scores than patients found to have non-stroke causes of their symptoms. The SL score correlated with the volume of ischemic brain tissue. These results demonstrate the feasibility of using lipid biomarkers to diagnose brain injury. Future studies will be needed to further characterize the diagnostic utility of this approach and to transition to an assay method applicable to clinical settings. PMID:26076478

  4. Clinical significance of serum thymus and activation-regulated chemokine in gastric cancer: Potential as a serum biomarker

    PubMed Central

    Lim, Jong-Baeck; Kim, Do-Kyun; Chung, Hye Won

    2014-01-01

    Thymus and activation-regulated chemokine (TARC) can stimulate cancer cell proliferation and migration. The present study evaluated the clinical significance of serum TARC in gastric cancer (GC). We measured serum TARC, macrophage-derived chemokine, monocyte chemotactic protein-1 and stem cell factor (SCF) levels using a chemiluminescent immunoassay along the GC carcinogenesis (normal, high-risk, early GC [EGC] and advanced GC [AGC]) in both training (N = 25 per group) and independent validation datasets (90 normal, 30 high-risk, 50 EGC and 50 AGC). Serum levels were compared among groups using one-way analysis of variance. To evaluate the diagnostic potential of serum TARC for GC, receiver operating characteristic curve and logistic regression analyses were performed. Correlations between serum TARC and GC clinicopathological features were analyzed using Spearman's correlation. In the training dataset, serum TARC correlated with serum MDC, MCP-1 and SCF. However, only serum TARC and SCF were significantly higher in cancer groups than non-cancer groups (P < 0.001). In the validation dataset, serum TARC also increased along the GC carcinogenesis; the AGC group (167.2 ± 111.1 ng/mL) had significantly higher levels than the EGC (109.1 ± 67.7 ng/mL), the high-risk (66.2 ± 47.7 ng/mL) and the normal (67.5 ± 36.2 ng/mL) groups (Bonferroni, all P < 0.001). Receiver operating characteristic curves and logistic regression demonstrated the remarkable diagnostic potential of serum TARC as a single marker (72.0% sensitivity and 71.1% specificity; cutoff point, 0.37; logistic regression) and in a multiple-marker panel (72.6% sensitivity and 88.2% specificity; cutoff point, 0.54). Spearman's correlation showed that serum TARC was closely correlated with tumor size (γs = 0.227, P = 0.028), T-stage (γs = 0.340, P = 0.001), N-stage (γs = 0.318, P = 0.002) and M-stage (γs = 0.346, P = 0.001). Serum TARC is a promising serum biomarker for GC

  5. miRNAs as serum biomarkers for Duchenne muscular dystrophy.

    PubMed

    Cacchiarelli, Davide; Legnini, Ivano; Martone, Julie; Cazzella, Valentina; D'Amico, Adele; Bertini, Enrico; Bozzoni, Irene

    2011-05-01

    Dystrophin absence in Duchenne muscular dystrophy (DMD) causes severe muscle degeneration. We describe that, as consequence of fibre damage, specific muscle-miRNAs are released in to the bloodstream of DMD patients and their levels correlate with the severity of the disease. The same miRNAs are abundant also in the blood of mdx mice and recover to wild-type levels in animals 'cured' through exon skipping. Even though creatine kinase (CK) blood levels have been utilized as diagnostic markers of several neuromuscular diseases, including DMD, we demonstrate that they correlate less well with the disease severity. Although the analysis of a larger number of patients should allow to obtain more refined correlations with the different stages of disease progression, we propose that miR-1, miR-133, and miR-206 are new and valuable biomarkers for the diagnosis of DMD and possibly also for monitoring the outcomes of therapeutic interventions in humans. Despite many different DMD therapeutic approaches are now entering clinical trials, a unifying method for assessing the benefit of different treatments is still lacking.

  6. Lung Cancer Serum Biomarker Discovery Using Label Free LC-MS/MS

    PubMed Central

    Zeng, Xuemei; Hood, Brian L.; Zhao, Ting; Conrads, Thomas P.; Sun, Mai; Gopalakrishnan, Vanathi; Grover, Himanshu; Day, Roger S.; Weissfeld, Joel L.; Wilson, David O.; Siegfried, Jill M.; Bigbee, William L.

    2011-01-01

    Introduction Lung cancer remains the leading cause of cancer-related death with poor survival due to the late stage at which lung cancer is typically diagnosed. Given the clinical burden from lung cancer, and the relatively favorable survival associated with early stage lung cancer, biomarkers for early detection of lung cancer are of important potential clinical benefit. Methods We performed a global lung cancer serum biomarker discovery study using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a set of pooled non-small cell lung cancer (NSCLC) case sera and matched controls. Immunoaffinity subtraction was used to deplete the top most abundant serum proteins; the remaining serum proteins were subjected to trypsin digestion and analyzed in triplicate by LC-MS/MS. The tandem mass spectrum data were searched against the human proteome database and the resultant spectral counting data were used to estimate the relative abundance of proteins across the case/control serum pools. The spectral counting derived abundances of some candidate biomarker proteins were confirmed with multiple reaction monitoring MS assays. Results A list of 49 differentially abundant candidate proteins was compiled by applying a negative binomial regression model to the spectral counting data (p<0.01). Functional analysis with Ingenuity Pathway Analysis tools showed significant enrichment of inflammatory response proteins, key molecules in cell-cell signaling and interaction network and differential physiological responses for the two common NSCLC subtypes. Conclusions We identified a set of candidate serum biomarkers with statistically significant differential abundance across the lung cancer case/control pools which, when validated, could improve lung cancer early detection. PMID:21304412

  7. Paired Serum and Urine Concentrations of Biomarkers of Diethyl Phthalate, Methyl Paraben, and Triclosan in Rats

    PubMed Central

    Teitelbaum, Susan L.; Li, Qian; Lambertini, Luca; Belpoggi, Fiorella; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Silva, Manori J.; Ye, Xiaoyun; Calafat, Antonia M.; Chen, Jia

    2015-01-01

    Background Exposure to environmental chemicals, including phthalates and phenols such as parabens and triclosan, is ubiquitous within the U.S. general population. Objective This proof-of-concept rodent study examined the relationship between oral doses of three widely used personal care product ingredients [diethyl phthalate (DEP), methyl paraben (MPB), and triclosan] and urine and serum concentrations of their respective biomarkers. Methods Using female Sprague-Dawley rats, we carried out two rounds of experiments with oral gavage doses selected in accordance with no observed adverse effect levels (NOAELs) derived from previous studies: 1,735 (DEP), 1,050 (MPB), 50 (triclosan) mg/kg/day. Administered doses ranged from 0.005 to 173 mg/kg/day, 10–100,000 times below the NOAEL for each chemical. Controls for the MPB and triclosan experiments were animals treated with olive oil (vehicle) only; controls for the DEP serum experiments were animals treated with the lowest doses of MPB and triclosan. Doses were administered for 5 days with five rats in each treatment group. Urine and blood serum, collected on the last day of exposure, were analyzed for biomarkers. Relationships between oral dose and biomarker concentrations were assessed using linear regression. Results Biomarkers were detected in all control urine samples at parts-per-billion levels, suggesting a low endemic environmental exposure to the three chemicals that could not be controlled even with all of the precautionary measures undertaken. Among the exposed animals, urinary concentrations of all three biomarkers were orders of magnitude higher than those in serum. A consistently positive linear relationship between oral dose and urinary concentration was observed (R2 > 0.80); this relationship was inconsistent in serum. Conclusions Our study highlights the importance of carefully considering the oral dose used in animal experiments and provides useful information in selecting doses for future studies

  8. A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans

    PubMed Central

    Bhomia, Manish; Balakathiresan, Nagaraja S.; Wang, Kevin K.; Papa, Linda; Maheshwari, Radha K.

    2016-01-01

    MicroRNAs (MiRNAs) are small endogenous RNA molecules and have emerged as novel serum diagnostic biomarkers for several diseases due to their stability and detection at minute quantities. In this study, we have identified a serum miRNA signature in human serum samples of mild to severe TBI, which can be used for diagnosis of mild and moderate TBI (MMTBI). Human serum samples of MMTBI, severe TBI (STBI), orthopedic injury and healthy controls were used and miRNA profiling was done using taqman real time PCR. The real time PCR data for the MMTBI, STBI and orthopedic injury was normalized to the control samples which showed upregulation of 39, 37 and 33 miRNAs in MMTBI, STBI and orthopedic injury groups respectively. TBI groups were compared to orthopedic injury group and an up-regulation of 18 and 20 miRNAs in MMTBI and STBI groups was observed. Among these, a signature of 10 miRNAs was found to be present in both MMTBI and STBI groups. These 10 miRNAs were validated in cerebrospinal fluid (CSF) from STBI and four miRNAs were found to be upregulated in CSF. In conclusion, we identified a subset of 10 unique miRNAs which can be used for diagnosis of MMTBI and STBI. PMID:27338832

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

    PubMed

    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

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

    PubMed Central

    Radhakrishnan, Preethi; Srikanth, Padma; Seshadri, Krishna G.; Barani, Ramya; Samanta, Maitreya

    2014-01-01

    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 < 0.001) was observed. Serum MCP-1 increased by 37.278 pg/ml for every 1% rise in HbA1c, and the levels were raised in group II and group III than in group I irrespective of their glycemic status. With an HbA1c range of 6.5-6.9% (group II), the serum MCP-1 values cluster around 380-410 pg/ml. Elevated levels of serum MCP-1 (>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. PMID:25143907

  11. PROTEOMIC PROFILING OF URINE IDENTIFIES SPECIFIC FRAGMENTS OF SERPINA-1 AND ALBUMIN AS BIOMARKERS OF PREECLAMPSIA

    PubMed Central

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

    2008-01-01

    Objective 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 pathophysiological understanding of preeclampsia. Study design Urine samples from 284 women were analyzed by mass spectrometry-based proteomics (SELDI). In the exploratory phase, 59 samples were used to extract the proteomic fingerprint characteristic of severe preeclampsia requiring mandated delivery and 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. 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 employed to identify, quantify and localize the biomarkers or related proteins. Results We report that women with preeclampsia appear to present a unique urine proteomic fingerprint which predicts preeclampsia in need for 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 >10 weeks prior to clinical manifestation. Tandem mass spectrometry followed by de-novo sequencing identified the biomarkers as non-random cleavage products of SERPINA-1 and albumin. Of these, the 21-aminoacid C-terminus fragment of SERPINA-1 was highly associated with severe forms of preeclampsia requiring early delivery. In preeclampsia, increased and

  12. Potential diagnostic and prognostic biomarkers for cholangiocarcinoma in serum and bile.

    PubMed

    Wang, Bin; Chen, Liang; Chang, Hao-Teng

    2016-06-01

    Cholangiocarcinoma (CCA) is a devastating malignancy that is difficult to treat because of its insensitivity to conventional therapies and the inability to detect early tumor formation. Novel molecular techniques have enabled the use of serum and bile markers for CCA diagnosis and prognosis. Herein, we summarize the principal characteristics of serum and bile markers of CCA. Biomarkers such as interleukin-6, matrix metalloproteinases, serotonin (5-hydroxytryptamine) and bile acids have shown promise for improving CCA diagnosis. Several markers such as CYFRA 21-1, MK-1 and C-reactive protein were recently shown to be effective for CCA prognosis. PMID:27232281

  13. Serum levels of phytoestrogens as biomarkers of intake in Mexican women.

    PubMed

    Palma-Duran, Susana Alejandra; Caire-Juvera, Graciela; Robles-Burgeño, María del Refugio; Ortega-Vélez, María Isabel; Gutiérrez-Coronado, María de Lourdes; Almada, María del Carmen Bermúdez; Chávez-Suárez, Karina; Campa-Siqueiros, Melissa; Grajeda-Cota, Patricia; Saucedo-Tamayo, María del Socorro; Valenzuela-Quintanar, Ana Isabel

    2015-01-01

    Phytoestrogens have generated interest in human health in view of their potential effect to reduce the risk of developing chronic diseases. Serum levels of phytoestrogens have been proposed as an alternative to measure the exposure of phytoestrogens. We evaluated the use of serum as a biomarker of phytoestrogen's intake in healthy women. Phytoestrogens in serum (luteolin, kaempferol, equol, biochanin A, formononetin, quercetin, naringenin, coumestrol, secoisolariciresinol, genistein, matairesinol, enterolactone, enterodiol, daidzein, glycitein and resveratrol) were analyzed by HPLC-ESI-MS. Subjects were asked to recall all foods and beverages consumed the previous 24 h. Association of dietary intake and serum concentrations was performed by Spearman correlation. Correlations were found for naringenin (r = 0.47, p < 0.001), luteolin (r = 0.4 p < 0.001), genistein (r = 0.32, p < 0.01) enterolactone (r = 0.35, p = 0.0553), coumestrol (r = 0.26, p = 0.0835) and resveratrol (r = 0.29, p = 0.0517). Serum levels as biomarkers of intake along with a 24-h recall would be useful in order to investigate the relationship between phytoestrogens and health.

  14. Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors

    PubMed Central

    Sandoval, John A.; Malkas, Linda H.; Hickey, Robert J.

    2012-01-01

    Childhood cancer is the leading cause of death by disease among U.S. children between infancy and age 15. Despite successes in treating solid tumors such as Wilms tumor, disappointments in the outcomes of high-risk solid tumors like neuroblastoma have precipitated efforts towards the early and accurate detection of these malignancies. This review summarizes available solid tumor serum biomarkers with a special focus on mediastinal and abdominal cancers in children. PMID:22312308

  15. Serum MicroRNA-4521 is a Potential Biomarker for Focal Cortical Dysplasia with Refractory Epilepsy.

    PubMed

    Wang, Xiaofeng; Sun, Yuqiang; Tan, Zeshi; Che, Ningwei; Ji, Anlong; Luo, Xiaodong; Sun, Xu; Li, Xinyu; Yang, Kang; Wang, Guanyu; Luan, Lan; Liu, Yaoling; Wei, Minghai; Yin, Jian

    2016-04-01

    Early biomarker-based diagnosis of focal cortical dysplasia (FCD) represents a major clinical challenge. The aim of this study was to identify novel brain microRNAs (miRNAs) in patients with refractory epilepsy and FCD as potential biomarkers. We evaluated serum hsa-miR-4521 as a promising novel biomarker in patients with FCD. Tissue for microarray was obtained from nine patients with temporal lobe refractory epilepsy who underwent surgery to remove epileptic foci identified by cortical video electroencephalogram monitoring. Control tissue was collected from eight patients with hypertension who required emergency surgery to remove an intracranial hematoma. The Affymetrix® GeneChip® Command Console® Software (Affymetrix miRNA 4.0) was used to compare miRNA expression in the cerebral cortex of experimental and control patients. Temporal cortex tissue and serum samples were taken from the same patients for verification of hsa-miR-4521 expression by real-time quantitative polymerase chain reaction (RT-qPCR). The experimental and control patients did not differ significantly in terms of age and gender. 19.4 % (148/764) of the total miRNAs were differentially expressed in experimental and control tissue, which is in agreement with the existing literature. We selected miRNA-4521 for further analysis; the fold-change in expression was 14.4707 and the q value was almost 0, which confirmed up-regulation. Significant up-regulation of hsa-miR-4521 was further validated by RT-qPCR. miRNA microarrays can efficiently and conveniently identify differentially expressed miRNAs in epilepsy brain tissue. This is the first study to identify differential expression of hsa-miR-4521 in brain tissue and serum of refractory epilepsy patients and suggests that serum hsa-miR-4521 may represent a potential diagnostic biomarker for FCD with refractory epilepsy.

  16. Chronic hepatitis C virus infection: Serum biomarkers in predicting liver damage

    PubMed Central

    Valva, Pamela; Ríos, Daniela A; De Matteo, Elena; Preciado, Maria V

    2016-01-01

    Currently, a major clinical challenge in the management of the increasing number of hepatitis C virus (HCV) infected patients is determining the best means for evaluating liver impairment. Prognosis and treatment of chronic hepatitis C (CHC) are partly dependent on the assessment of histological activity, namely cell necrosis and inflammation, and the degree of liver fibrosis. These parameters can be provided by liver biopsy; however, in addition to the risks related to an invasive procedure, liver biopsy has been associated with sampling error mostly due to suboptimal biopsy size. To avoid these pitfalls, several markers have been proposed as non-invasive alternatives for the diagnosis of liver damage. Distinct approaches among the currently available non-invasive methods are (1) the physical ones based on imaging techniques; and (2) the biological ones based on serum biomarkers. In this review, we discuss these approaches with special focus on currently available non-invasive serum markers. We will discuss: (1) class I serum biomarkers individually and as combined panels, particularly those that mirror the metabolism of liver extracellular matrix turnover and/or fibrogenic cell changes; (2) class II biomarkers that are indirect serum markers and are based on the evaluation of common functional alterations in the liver; and (3) biomarkers of liver cell death, since hepatocyte apoptosis plays a significant role in the pathogenesis of HCV infection. We highlight in this review the evidence behind the use of these markers and assess the diagnostic accuracy as well as advantages, limitations, and application in clinical practice of each test for predicting liver damage in CHC. PMID:26819506

  17. A Multiplexed Device Based on Tunable Nanoshearing for Specific Detection of Multiple Protein Biomarkers in Serum

    PubMed Central

    Vaidyanathan, Ramanathan; van Leeuwen, Lara Michelle; Rauf, Sakandar; Shiddiky, Muhammad J. A.; Trau, Matt

    2015-01-01

    Microfluidic flow based multiplexed devices have gained significant promise in detecting biomarkers in complex biological samples. However, to fully exploit their use in bioanalysis, issues such as (i) low sensitivity and (ii) high levels of nonspecific adsorption of non-target species have to be overcome. Herein, we describe a new multiplexed device for the sensitive detection of multiple protein biomarkers in serum by using an alternating current (ac) electrohydrodynamics (ac-EHD) induced surface shear forces based phenomenon referred to as nanoshearing. The tunable nature (via manipulation of ac field) of these nanoshearing forces can alter the capture performance of the device (e.g., improved fluid transport enhances number of sensor-target collisions). This can also selectively displace weakly (nonspecifically) bound molecules from the electrode surface (i.e., fluid shear forces can be tuned to shear away nonspecific species present in biological samples). Using this approach, we achieved sensitive (100 fg mL−1) naked eye detection of multiple protein targets spiked in human serum and a 1000-fold enhancement in comparison to hydrodynamic flow based devices for biomarker detection. We believe that this approach could potentially represent a clinical diagnostic tool that can be integrated into resource-limited settings for sensitive detection of target biomarkers using naked eye. PMID:25978807

  18. Systemic Disease-Induced Salivary Biomarker Profiles in Mouse Models of Melanoma and Non-Small Cell Lung Cancer

    PubMed Central

    Gao, Kai; Zhou, Hui; Zhang, Lei; Lee, Jin Wook; Zhou, Qing; Hu, Shen; Wolinsky, Lawrence E.; Farrell, James; Eibl, Guido; Wong, David T.

    2009-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions 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. PMID:19517020

  19. Hydroxyproline, a serum biomarker candidate for gastric ulcer in rats: a comparison study of metabolic analysis of gastric ulcer models induced by ethanol, stress, and aspirin.

    PubMed

    Takeuchi, Kenichiro; Ohishi, Maki; Endo, Keiko; Suzumura, Kenichi; Naraoka, Hitoshi; Ohata, Takeji; Seki, Jiro; Miyamae, Yoichi; Honma, Masashi; Soga, Tomoyoshi

    2014-01-01

    Gastrointestinal symptoms are a common manifestation of adverse drug effects. Non-steroid anti-inflammatory drugs (NSAIDs) are widely prescribed drugs that induce the serious side effect of gastric mucosal ulceration. Biomarkers for these side effects have not been identified and ulcers are now only detectable by endoscopy. We previously identified five metabolites as biomarker candidates for NSAID-induced gastric ulcer using capillary electrophoresis-mass spectrometry (CE-MS)-based metabolomic analysis of serum and stomach from rats. Here, to clarify mechanism of changes and limitations of indications of biomarker candidates, we performed CE-MS-based metabolomic profiling in stomach and serum from rats with gastric ulcers induced by ethanol, stress, and aspirin. The results suggest that a decrease in hydroxyproline reflects the induction of gastric injury and may be useful in identifying gastric ulcer induced by multiple causes. While extrapolation to humans requires further study, hydroxyproline can be a new serum biomarker of gastric injury regardless of cause. PMID:25125970

  20. Utilization of metabonomics to identify serum biomarkers in murine H22 hepatocarcinoma and deduce antitumor mechanism of Rhizoma Paridis saponins.

    PubMed

    Qiu, Peiyu; Man, Shuli; Yang, He; Fan, Wei; Yu, Peng; Gao, Wenyuan

    2016-08-25

    Murine H22 hepatocarcinoma model is so popular to be used for the preclinical anticancer candidate's evaluation. However, the metabolic biomarkers of this model were not identified. Meanwhile, Rhizoma Paridis saponins (RPS) as natural products have been found to show strong antitumor activity, while its anti-cancer mechanism is not clear. To search for potential metabolite biomarkers of this model, serum metabonomics approach was applied to detect the variation of metabolite biomarkers and the related metabolism genes and signaling pathway were used to deduce the antitumor mechanisms of RPS. As a result, ten serum metabolites were identified in twenty-four mice including healthy mice, non-treated cancer mice, RPS-treated cancer mice and RPS-treated healthy mice. RPS significantly decreased tumor weight correlates to down-regulating lactate, acetate, N-acetyl amino acid and glutamine signals (p < 0.05), which were marked metabolites screened according to the very important person (VIP), loading plot and receiver operating characteristic curve (ROC) tests. For the analysis of metabolic enzyme related genes, RPS reversed the aerobic glycolysis through activating tumor suppressor p53 and PTEN, and suppressed FASN to inhibit lipogenesis. What's more, RPS repressed Myc and GLS expression and decreased glutamine level. The regulating PI3K/Akt/mTOR and HIF-1α/Myc/Ras networks also participated in these metabolic changes. Taken together, RPS suppressed ATP product made the tumor growth slow, which indicated a good anti-cancer effect and new angle for understanding the mechanism of RPS. In conclusion, this study demonstrated that the utility of (1)H NMR metabolic profiles taken together with tumor weight and viscera index was a promising screening tool for evaluating the antitumor effect of candidates. In addition, RPS was a potent anticancer agent through inhibiting cancer cellular metabolism to suppress proliferation in hepatoma H22 tumor murine, which promoted the

  1. Serum metabolic profiling of abnormal savda by liquid chromatography/mass spectrometry.

    PubMed

    Yin, Peiyuan; Mohemaiti, Patamu; Chen, Jing; Zhao, Xinjie; Lu, Xin; Yimiti, Adilijiang; Upur, Halmurat; Xu, Guowang

    2008-08-15

    Abnormal savda is a special symptom in Uigur medicine. The understanding of its metabolic origins is of great importance for the subsequent treatment. Here, a metabonomic study of this symptom was carried out using LC-MS based human serum metabolic profiling. Orthogonal signal correction partial least-squares discriminant analysis (OSC-PLS-DA) was used for the classification and prediction of abnormal savda. Potential biomarkers from metabonomics were also identified for a metabolic understanding of abnormal savda. As a result, our OSC-PLS-DA model had a satisfactory ability for separation and prediction of abnormal savda. The potential biomarkers including bilirubin, bile acids, tryptophan, phenylalanine and lyso-phosphatidylcholines indicated that abnormal savda could be related to some abnormal metabolisms within the body, including energy metabolism, absorption of nutrition, metabolism of lecithin on cell membrane, etc. To the best of our knowledge, this is the first study of abnormal savda based on serum metabolic profiling. The LC/MS-based metabonomic platform could be a powerful tool for the classification of symptoms and for the development of this traditional medicine into an evidence-based one.

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

    PubMed Central

    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

    2016-01-01

    AIM: To clarify the characteristics of metabolite profiles in virus-related hepatocellular carcinoma (HCC) patients using serum metabolome analysis. METHODS: 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. RESULTS: 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). CONCLUSION: 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. PMID:27468212

  3. Identification of serum biomarkers in dogs naturally infected with Babesia canis canis using a proteomic approach

    PubMed Central

    2014-01-01

    Background Canine babesiosis is a tick-borne disease that is caused by the haemoprotozoan parasites of the genus Babesia. There are limited data on serum proteomics in dogs, and none of the effect of babesiosis on the serum proteome. The aim of this study was to identify the potential serum biomarkers of babesiosis using proteomic techniques in order to increase our understanding about disease pathogenesis. Results Serum samples were collected from 25 dogs of various breeds and sex with naturally occurring babesiosis caused by B. canis canis. Blood was collected on the day of admission (day 0), and subsequently on the 1st and 6th day of treatment. Two-dimensional electrophoresis (2DE) of pooled serum samples of dogs with naturally occurring babesiosis (day 0, day 1 and day 6) and healthy dogs were run in triplicate. 2DE image analysis showed 64 differentially expressed spots with p ≤ 0.05 and 49 spots with fold change ≥2. Six selected spots were excised manually and subjected to trypsin digest prior to identification by electrospray ionisation mass spectrometry on an Amazon ion trap tandem mass spectrometry (MS/MS). Mass spectrometry data was processed using Data Analysis software and the automated Matrix Science Mascot Daemon server. Protein identifications were assigned using the Mascot search engine to interrogate protein sequences in the NCBI Genbank database. A number of differentially expressed serum proteins involved in inflammation mediated acute phase response, complement and coagulation cascades, apolipoproteins and vitamin D metabolism pathway were identified in dogs with babesiosis. Conclusions Our findings confirmed two dominant pathogenic mechanisms of babesiosis, haemolysis and acute phase response. These results may provide possible serum biomarker candidates for clinical monitoring of babesiosis and this study could serve as the basis for further proteomic investigations in canine babesiosis. PMID:24885808

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

    PubMed Central

    Herrick, Robert F; Meeker, John D; Hauser, Russ; Altshul, Larisa; Weymouth, George A

    2007-01-01

    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 a major source of PCB

  5. Preliminary Study on Serum Lactate Dehydrogenase (LDH)-Prognostic Biomarker in Carcinoma Breast

    PubMed Central

    Gandhe, Mahendra Bhauraoji; Gupta, Dilip; Reddy, M.V.R.

    2016-01-01

    Introduction Serum Lactate Dehydrogenase (LDH) is one of the biochemical markers for breast cancer. Serum LDH is enzyme required for anaerobic glycolysis. One of its isoenzyme is increased in breast cancer due to up-regulation in its gene. It leads to increase in serum LDH level in breast cancer patients. Serum LDH is economical, easily available and easy to estimate. Aim In the present study, we evaluated the LDH levels in circulation of newly diagnosed patients of breast cancer and tried to correlate it with different TNM staging of carcinoma breast before interventions and after adjuvant therapy of these patients. Materials and Methods This prospective study was done on 83 diagnosed patients of breast cancer was conducted among poor patients in rural area. This study was conducted in the Department of Surgery between October 2008 to October 2010, at MGIMS, Sevagram, Maharashtra, a rural medical college located in Central India. Out of total 83 participants, 10 participants were having adverse events following surgery and remaining 73 participants were without adverse events following surgery. The significant difference in serum LDH levels between two groups, with and without adverse surgical outcome was calculated by Mann-Whitney U test. Results Patients with higher clinical TNM staging were having higher serum LDH levels. The serum LDH levels at sixth months following surgery showed a trend of statistically significant difference between patients with and without adverse events. As increased serum LDH levels in breast cancer patients shows poor prognosis, surgical outcome or advanced metastases. Conclusion Serum LDH monitoring can be used as a prognostic biomarker in patients of breast cancer. For confirmation of this finding, we require further more studies on larger sample size and long-term follow-up in patients specifically with higher serum LDH levels. PMID:27134855

  6. Integrated microfluidic device for serum biomarker quantitation using either standard addition or a calibration curve.

    PubMed

    Yang, Weichun; Sun, Xiuhua; Wang, Hsiang-Yu; Woolley, Adam T

    2009-10-01

    Detection and accurate quantitation of biomarkers such as alpha-fetoprotein (AFP) can be a key aspect of early stage cancer diagnosis. Microfluidic devices provide attractive analysis capabilities, including low sample and reagent consumption, as well as short assay times. However, to date microfluidic analyzers have relied almost exclusively on calibration curves for sample quantitation, which can be problematic for complex mixtures such as human serum. We have fabricated integrated polymer microfluidic systems that can quantitatively determine fluorescently labeled AFP in human serum using either the method of standard addition or a calibration curve. Our microdevices couple an immunoaffinity purification step with rapid microchip electrophoresis separation in a laser-induced fluorescence detection system, all under automated voltage control in a miniaturized polymer microchip. In conjunction with laser-induced fluorescence detection, these systems can quantify AFP at approximately 1 ng/mL levels in approximately 10 microL of human serum in a few tens of minutes. Our polymer microdevices have been applied in determining AFP in spiked serum samples. These integrated microsystems offer excellent potential for rapid, simple, and accurate biomarker quantitation in a point-of-care setting.

  7. Serum Nutritional Biomarkers and Their Associations with Sleep among US Adults in Recent National Surveys

    PubMed Central

    Beydoun, May A.; Gamaldo, Alyssa A.; Canas, Jose A.; Beydoun, Hind A.; Shah, Mauli T.; McNeely, Jessica M.; Zonderman, Alan B.

    2014-01-01

    Background The associations between nutritional biomarkers and measures of sleep quantity and quality remain unclear. Methods 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(OH)D) and vitamin E. Main analyses consisted of multiple linear, logistic and multinomial logit models. Results Among key findings, independent inverse associations were found between serum vitamin B-12 and sleep duration, 25(OH)D 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). Conclusions 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. PMID:25137304

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

    PubMed

    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.

  9. Early and delayed effects of naturally occurring asbestos on serum biomarkers of inflammation and metabolism.

    PubMed

    Kodavanti, Urmila P; Andrews, Debora; Schladweiler, Mette C; Gavett, Stephen H; Dodd, Darol E; Cyphert, Jaime M

    2014-01-01

    Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; α-2 macroglobulin, A2M; and α-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 μm) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance.

  10. Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer.

    PubMed

    Keeley, Brieze R; Islami, Farhad; Pourshams, Akram; Poustchi, Hossein; Pak, Jamie S; Brennan, Paul; Khademi, Hooman; Genden, Eric M; Abnet, Christian C; Dawsey, Sanford M; Boffetta, Paolo; Malekzadeh, Reza; Sikora, Andrew G

    2014-09-01

    This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case-control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21 cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin-1Rα (IL-1Ra; 35.9), interferon α2 (IFN-a2; 34.0), fibroblast growth factor-2 (FGF-2; 17.4), and granulocyte/macrophage colony-stimulating factor (GM-CSF; 17.4). The same pattern was observed among future lung cancer cases for G-CSF (27.7), GM-CSF (13.3), and tumor necrosis factor-α (TNF-a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis. PMID:25040886

  11. Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer

    PubMed Central

    Keeley, Brieze R; Islami, Farhad; Pourshams, Akram; Poustchi, Hossein; Pak, Jamie S; Brennan, Paul; Khademi, Hooman; Genden, Eric M; Abnet, Christian C; Dawsey, Sanford M; Boffetta, Paolo; Malekzadeh, Reza; Sikora, Andrew G

    2014-01-01

    This study tests the hypothesis that prediagnostic serum levels of 20 cancer-associated inflammatory biomarkers correlate directly with future development of head and neck, esophageal, and lung cancers in a high-risk prospective cohort. This is a nested case–control pilot study of subjects enrolled in the Golestan Cohort Study, an ongoing epidemiologic project assessing cancer trends in Golestan, Iran. We measured a panel of 20 21cytokines, chemokines, and inflammatory molecules using Luminex technology in serum samples collected 2 or more years before cancer diagnosis in 78 aerodigestive cancer cases and 81 controls. Data was analyzed using Wilcoxon rank sum test, odds ratios, receiver operating characteristic areas of discrimination, and multivariate analysis. Biomarkers were profoundly and globally elevated in future esophageal and lung cancer patients compared to controls. Odds ratios were significant for association between several biomarkers and future development of esophageal cancer, including interleukin-1Rα (IL-1Ra; 35.9), interferon α2 (IFN-a2; 34.0), fibroblast growth factor-2 (FGF-2; 17.4), and granulocyte/macrophage colony-stimulating factor (GM-CSF; 17.4). The same pattern was observed among future lung cancer cases for G-CSF (27.7), GM-CSF (13.3), and tumor necrosis factor-α (TNF-a; 8.6). By contrast, the majority of biomarkers studied showed no significant correlation with future head and neck cancer development. This study provides the first direct evidence that multiple inflammatory biomarkers are coordinately elevated in future lung and esophageal cancer patients 2 or more years before cancer diagnosis. PMID:25040886

  12. Prognostic serum miRNA biomarkers associated with Alzheimer's disease shows concordance with neuropsychological and neuroimaging assessment.

    PubMed

    Cheng, L; Doecke, J D; Sharples, R A; Villemagne, V L; Fowler, C J; Rembach, A; Martins, R N; Rowe, C C; Macaulay, S L; Masters, C L; Hill, A F

    2015-10-01

    There is no consensus for a blood-based test for the early diagnosis of Alzheimer's disease (AD). Expression profiling of small non-coding RNA's, microRNA (miRNA), has revealed diagnostic potential in human diseases. Circulating miRNA are found in small vesicles known as exosomes within biological fluids such as human serum. The aim of this work was to determine a set of differential exosomal miRNA biomarkers between healthy and AD patients, which may aid in diagnosis. Using next-generation deep sequencing, we profiled exosomal miRNA from serum (N=49) collected from the Australian Imaging, Biomarkers and Lifestyle Flagship Study (AIBL). Sequencing results were validated using quantitative reverse transcription PCR (qRT-PCR; N=60), with predictions performed using the Random Forest method. Additional risk factors collected during the 4.5-year AIBL Study including clinical, medical and cognitive assessments, and amyloid neuroimaging with positron emission tomography were assessed. An AD-specific 16-miRNA signature was selected and adding established risk factors including age, sex and apolipoprotein ɛ4 (APOE ɛ4) allele status to the panel of deregulated miRNA resulted in a sensitivity and specificity of 87% and 77%, respectively, for predicting AD. Furthermore, amyloid neuroimaging information for those healthy control subjects incorrectly classified with AD-suggested progression in these participants towards AD. These data suggest that an exosomal miRNA signature may have potential to be developed as a suitable peripheral screening tool for AD. PMID:25349172

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

    PubMed Central

    Khadem Haghighian, Mahdieh; Alipoor, Beitollah; Eftekhar Sadat, Bina; Malek Mahdavi, Aida; Moghaddam, Abdolvahab; Vatankhah, Amir-Mansour

    2014-01-01

    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 (P<0.05), while no significant difference in serum values of lipid profile and oxidative stress parameters was seen in the control group (P>0.05). 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. PMID:25097842

  14. A Panel of Serum Biomarkers Differentiates IgA Nephropathy from Other Renal Diseases

    PubMed Central

    Suzuki, Yusuke; Kiryluk, Krzysztof; Gharavi, Ali G.; Matsuoka, Kiyoshi; Makita, Yuko; Julian, Bruce A.; Novak, Jan; Tomino, Yasuhiko

    2014-01-01

    Background and Objectives There is increasing evidence that galactose-deficient IgA1 (Gd-IgA1) and Gd-IgA1-containing immune complexes are important for the pathogenesis of IgA nephropathy (IgAN). In the present study, we assessed a novel noninvasive multi-biomarker approach in the diagnostic test for IgAN. Materials and Methods We compared serum levels of IgA, IgG, Gd-IgA1, Gd-IgA1-specific IgG and Gd-IgA1-specific IgA in 135 IgAN patients, 79 patients with non-IgAN chronic kidney disease (CKD) controls and 106 healthy controls. Serum was collected at the time of kidney biopsy from all IgAN and CKD patients. Results Each serum marker was significantly elevated in IgAN patients compared to CKD (P<0.001) and healthy controls (P<0.001). While 41% of IgAN patients had elevated serum Gd-IgA1 levels, 91% of these patients exhibited Gd-IgA1-specific IgG levels above the 90th percentile for healthy controls (sensitivity 89%, specificity 92%). Although up to 25% of CKD controls, particularly those with immune-mediated glomerular diseases including lupus nephritis, also had elevated serum levels of Gd-IgA1-specific IgG, most IgAN patients had elevated levels of Gd-IgA1-specific antibody of both isotypes. Serum levels of Gd-IgA1-specific IgG were associated with renal histological grading. Furthermore, there was a trend toward higher serum levels of Gd-IgA1-specific IgG in IgAN patients with at least moderate proteinuria (≥1.0 g/g), compared to patients with less proteinuria. Conclusions Serum levels of Gd-IgA1-specific antibodies are elevated in most IgAN patients, and their assessment, together with serum levels of Gd-IgA1, improves the specificity of the assays. Our observations suggest that a panel of serum biomarkers may be helpful in differentiating IgAN from other glomerular diseases. PMID:24858067

  15. Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth

    PubMed Central

    Jelliffe-Pawlowski, LL; Baer, RJ; Blumenfeld, YJ; Ryckman, KK; O’Brodovich, HM; Gould, JB.; Druzin, ML; El-Sayed, YY; Lyell, DJ; Stevenson, DK; Shaw, GM; Currier, RJ

    2015-01-01

    Objective To examine the relationship between maternal characteristics, serum biomarkers, and preterm birth (PTB) by spontaneous and medically-indicated subtypes. Design Population-based cohort. Setting California, United States of America. Population From a total population of 1,004,039 live singleton births in 2009 and 2010, 841,665 pregnancies with linked birth certificate and hospital discharge records were included. Methods Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models (adjORs) and 95% confidence intervals (CIs). First and second trimester serum marker levels were analyzed in a subset of 125,202 pregnancies with available first and second trimester serum biomarker results. Main Outcome Measure PTB by subtype. Results In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, preexisting hypertension with and without preeclampsia, gestational hypertension with preeclampsia, preexisting diabetes, anemia, previous PTB, one or ≥ two previous cesarean section(s), interpregnancy interval ≥ 60 months, low first trimester pregnancy-associated plasma protein A, high second trimester alpha-fetoprotein, and high second trimester dimeric inhibin A). These risks occurred in 51.6 to 86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically-indicated PTB < 32 weeks in women with preexisting hypertension and preeclampsia (adjOR 89.7, 27.3 – 111.2). Conclusions Our findings suggest a shared etiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies. PMID:26111589

  16. Solid tumors of childhood display specific serum microRNA profiles

    PubMed Central

    Murray, Matthew J.; Raby, Katie L.; Saini, Harpreet K.; Bailey, Shivani; Wool, Sophie V.; Tunnacliffe, Jane M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

    2014-01-01

    Background Serum biomarkers for diagnosis and risk-stratification of childhood solid tumors would improve the accuracy/timeliness of diagnosis and reduce the need for invasive biopsies. We hypothesized that differential expression and/or release of microRNAs by such tumors may be detected as altered serum microRNA profiles. Methods We undertook global quantitative-RT-PCR microRNA profiling (n=741) on RNA from 53 serum samples, representing 33 diagnostic cases of common childhood cancers plus 20 controls. Technical confirmation was performed in a subset of 21 cases, plus four independent samples. Results We incorporated robust quality-control steps for RNA extraction, qRT-PCR efficiency and hemolysis quantification. We evaluated multiple methods to normalize global profiling data and identified the ‘global-mean’ approach as optimal. We generated a panel of six microRNAs that were most stable in pediatric serum samples and therefore most suitable for normalization of targeted microRNA qRT-PCR data. Tumor-specific serum microRNA profiles were identified for each tumor type and selected microRNAs underwent confirmatory testing. We identified a panel of microRNAs (miR-124-3p/miR-9-3p/miR-218-5p/miR-490-5p/miR-1538) of potential importance in the clinical management of neuroblastoma, as they were consistently highly over-expressed in MYCN-amplified high-risk cases (MYCN-NB). We also derived candidate microRNA panels for non-invasive differential diagnosis of a liver mass (hepatoblastoma vs. combined MYCN-NB/NB), an abdominal mass (Wilms tumor vs. combined MYCN-NB/NB), and sarcoma subtypes. Conclusions This study describes a pipeline for robust diagnostic serum microRNA profiling in childhood solid tumors, and has identified candidate microRNA profiles for prospective testing. Impact We propose a new non-invasive method with the potential to diagnose childhood solid tumors. PMID:25416717

  17. Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis.

    PubMed

    Kamiya, Yasuko; Kawada, Jun-ichi; Kawano, Yoshihiko; Torii, Yuka; Kawabe, Shinji; Iwata, Naomi; Ito, Yoshinori

    2015-10-01

    MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression of targeted mRNAs, which are important in the pathogenesis of autoimmune diseases. MiRNAs may have the potential to serve as biomarkers of disease. We evaluated serum levels of selected miRNAs and their associations with disease activity in juvenile idiopathic arthritis (JIA). Sera and peripheral blood leukocytes were collected from patients with JIA (8 systemic onset, 16 polyarthritis) and healthy controls. Levels of miR-16, miR-132, miR-146a, miR-155, and miR-223 were quantified. Levels of miR-223 in sera were significantly higher in patients in the active phase of systemic onset JIA than in controls. MiRNAs of peripheral blood leukocytes did not exhibit any difference between patients with JIA and controls. In both systemic onset JIA and polyarthritis patients, levels of miR-223 and miR-16 correlated with erythrocyte sedimentation rate and matrix metalloproteinase-3, respectively. MiR-146a and miR-223 in polyarthritis showed correlations with matrix metalloproteinase-3. Expressions of miRNAs were altered in patients with JIA. Serum levels of miR-223 may be a potential disease biomarker. Investigation of miRNAs could be helpful in understanding the pathogenesis of JIA and could aid in the identification of additional disease biomarkers.

  18. LC-MS/MS-based serum proteomics for identification of candidate biomarkers for hepatocellular carcinoma.

    PubMed

    Tsai, Tsung-Heng; Song, Ehwang; Zhu, Rui; Di Poto, Cristina; Wang, Minkun; Luo, Yue; Varghese, Rency S; Tadesse, Mahlet G; Ziada, Dina Hazem; Desai, Chirag S; Shetty, Kirti; Mechref, Yehia; Ressom, Habtom W

    2015-07-01

    Associating changes in protein levels with the onset of cancer has been widely investigated to identify clinically relevant diagnostic biomarkers. In the present study, we analyzed sera from 205 patients recruited in the United States and Egypt for biomarker discovery using label-free proteomic analysis by LC-MS/MS. We performed untargeted proteomic analysis of sera to identify candidate proteins with statistically significant differences between hepatocellular carcinoma (HCC) and patients with liver cirrhosis. We further evaluated the significance of 101 proteins in sera from the same 205 patients through targeted quantitation by MRM on a triple quadrupole mass spectrometer. This led to the identification of 21 candidate protein biomarkers that were significantly altered in both the United States and Egyptian cohorts. Among the 21 candidates, ten were previously reported as HCC-associated proteins (eight exhibiting consistent trends with our observation), whereas 11 are new candidates discovered by this study. Pathway analysis based on the significant proteins reveals upregulation of the complement and coagulation cascades pathway and downregulation of the antigen processing and presentation pathway in HCC cases versus patients with liver cirrhosis. The results of this study demonstrate the power of combining untargeted and targeted quantitation methods for a comprehensive serum proteomic analysis, to evaluate changes in protein levels and discover novel diagnostic biomarkers. All MS data have been deposited in the ProteomeXchange with identifier PXD001171 (http://proteomecentral.proteomexchange.org/dataset/PXD001171).

  19. Serum carnitine as an independent biomarker of malnutrition in patients with impaired oral intake

    PubMed Central

    Iwamoto, Junichi; Honda, Akira; Miyamoto, Yasunori; Miyazaki, Teruo; Murakami, Masashi; Saito, Yoshifumi; Ikegami, Tadashi; Miyamoto, Jiro; Matsuzaki, Yasushi

    2014-01-01

    Carnitine is a vitamin-like compound that plays important roles in fatty acid β-oxidation and the control of the mitochondrial coenzyme A/acetyl-CoA ratio. However, carnitine is not added to ordinary enteral nutrition or total parenteral nutrition. In this study, we determined the serum carnitine concentrations in subjects receiving ordinary enteral nutrition (EN) or total parenteral nutrition (TPN) and in patients with inflammatory bowel diseases to compare its levels with those of other nutritional markers. Serum samples obtained from 11 EN and 11 TPN patients and 82 healthy controls were examined. In addition, 10 Crohn’s disease and 10 ulcerative colitis patients with malnutrition who were barely able to ingest an ordinary diet were also evaluated. Carnitine and its derivatives were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The carnitine concentrations in EN and TPN subjects were significantly lower compared with those of the control subjects. Neither the serum albumin nor the total cholesterol level was correlated with the carnitine concentration, although a significant positive correlation was found between the serum albumin and total cholesterol levels. Indeed, patients with CD and UC showed significantly reduced serum albumin and/or total cholesterol levels, but their carnitine concentrations remained normal. In conclusion, only a complete blockade of an ordinary diet, such as EN or TPN, caused a reduction in the serum carnitine concentration. Serum carnitine may be an independent biomarker of malnutrition, and its supplementation is needed in EN and TPN subjects even if their serum albumin and total cholesterol levels are normal. PMID:25411530

  20. Serial serum alkaline phosphatase as an early biomarker for osteopenia of prematurity.

    PubMed

    Abdallah, Enas A A; Said, Reem N; Mosallam, Dalia S; Moawad, Eman M I; Kamal, Naglaa M; Fathallah, Mohammed G E-D

    2016-09-01

    Metabolic bone disease of prematurity is a condition characterized by reduction in bone mineral content (osteopenia). It is a problem faced by very low birth weight (VLBW) infants because of lack of fetal mineralization during the last trimester. Our aim was to assess serum alkaline phosphatase (ALP) level as an early biomarker for osteopenia in premature infants and to estimate an optimal cutoff value of serum ALP at which osteopenia is detected radiologically in premature newborns.This prospective study was conducted on a cohort of 120 newborn infants of both sex of ≤34 weeks' gestational age and <1500 g birth weight. Two blood samples, from each infant on at least 2 consecutive weeks, were reported for calcium, phosphorus, and ALP. Evidence of osteopenia was evaluated radiologically by performing wrist/knee x-ray.Sixteen infants (13.3%) had evidence of osteopenia in x-ray, whereas 104 infants (86.7%) were nonosteopenic and all the osteopenic infants were <1000-g birth weight. Birth weight and gestational age were significantly inversely related to serum ALP levels. Both samples showed statistically significantly higher mean ALP level in osteopenic than nonosteopenics (P < 0.001, and P < 0.001 respectively). There was no constant value of serum ALP related to radiologic evidence of osteopenia. However, the optimal cutoff value of serum ALP at which osteopenia is detected is 500 IU/L with 100% sensitivity and 80.77% specificity.High levels of ALP can be considered a reliable biomarker to predict the status of bone mineralization and the need for radiological evaluation in premature infants particularly those <1000-g birth weight and <32 weeks' gestation. PMID:27631238

  1. Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.

    PubMed

    Wood, Adrian D; Strachan, Anna A; Thies, Frank; Aucott, Lorna S; Reid, David M; Hardcastle, Antonia C; Mavroeidi, Alexandra; Simpson, William G; Duthie, Garry G; Macdonald, Helen M

    2014-10-28

    Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised β for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit

  2. Preemptive tumor profiling for biomarker-stratified early clinical drug development in metastatic breast cancer patients.

    PubMed

    Welt, Anja; Tewes, Mitra; Aktas, Bahriye; O Hoffmann, Oliver; Wiesweg, Marcel; Ting, Saskia; Reis, Henning; Worm, Karl; Richly, Heike; Hense, Jörg; Palmer, Michael R; Lee, Benjamin H; Wendling, Johanna; Kossow, Josef; Scheulen, Max E; Lehnerdt, Cathrin; Kohl, Marzena; Derks, Cordula; Skottky, Silke; Haus, Ulrike; Schmid, Kurt W; Kimmig, Rainer; Schuler, Martin; Kasper, Stefan

    2013-11-01

    Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly incorporated in early clinical trials, thus demanding a new process of patient selection. Here, we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic breast cancer patients treated at the West German Cancer Center. Profiling for experimental biomarkers was prospectively offered to patients with metastatic breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially “actionable” biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in situ hybridization. The clinical course of those “profiled” patients was closely monitored to offer trial participation whenever applicable. Here, we report results from the first 131 patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2 %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected next to established biomarkers such as estrogen (67 %) and progesterone receptor expression (52 %), and HER2 overexpression or amplification (23 %). So far 16 “profiled” patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required

  3. Cancer serum biomarkers based on aberrant post-translational modifications of glycoproteins: Clinical value and discovery strategies.

    PubMed

    Silva, M Luísa S

    2015-12-01

    Due to the increase in life expectancy in the last decades, as well as changes in lifestyle, cancer has become one of the most common diseases both in developed and developing countries. Early detection remains the most promising approach to improve long-term survival of cancer patients and this may be achieved by efficient screening of biomarkers in biological fluids. Great efforts have been made to identify specific alterations during oncogenesis. Changes at the cellular glycosylation profiles are among such alterations. The "glycosylation machinery" of cells is affected by malignant transformation due to the altered expression of glycogens, leading to changes in glycan biosynthesis and diversity. Alterations in the post-translational modifications of proteins that occur in cancer result in the expression of antigenically distinct glycoproteins. Therefore, these aberrant and cancer-specific glycoproteins and the autoantibodies that are produced in response to their presence constitute targets for cancer biomarkers' search. Different strategies have been implemented for the discovery of cancer glycobiomarkers and are herein reviewed, along with their potentialities and limitations. Practical issues related with serum analysis are also addressed, as well as the challenges that this area faces in the near future.

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

    PubMed Central

    Zhao, Pengxin; Zhang, Kaili

    2016-01-01

    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. PMID:27446209

  5. SELDI-TOF-MS Proteomic Profiling of Serum, Urine, and Amniotic Fluid in Neural Tube Defects

    PubMed Central

    Liu, Zhenjiang; Yuan, Zhengwei; Zhao, Qun

    2014-01-01

    Neural tube defects (NTDs) are common birth defects, whose specific biomarkers are needed. The purpose of this pilot study is to determine whether protein profiling in NTD-mothers differ from normal controls using SELDI-TOF-MS. ProteinChip Biomarker System was used to evaluate 82 maternal serum samples, 78 urine samples and 76 amniotic fluid samples. The validity of classification tree was then challenged with a blind test set including another 20 NTD-mothers and 18 controls in serum samples, and another 19 NTD-mothers and 17 controls in urine samples, and another 20 NTD-mothers and 17 controls in amniotic fluid samples. Eight proteins detected in serum samples were up-regulated and four proteins were down-regulated in the NTD group. Four proteins detected in urine samples were up-regulated and one protein was down-regulated in the NTD group. Six proteins detected in amniotic fluid samples were up-regulated and one protein was down-regulated in the NTD group. The classification tree for serum samples separated NTDs from healthy individuals, achieving a sensitivity of 91% and a specificity of 97% in the training set, and achieving a sensitivity of 90% and a specificity of 97% and a positive predictive value of 95% in the test set. The classification tree for urine samples separated NTDs from controls, achieving a sensitivity of 95% and a specificity of 94% in the training set, and achieving a sensitivity of 89% and a specificity of 82% and a positive predictive value of 85% in the test set. The classification tree for amniotic fluid samples separated NTDs from controls, achieving a sensitivity of 93% and a specificity of 89% in the training set, and achieving a sensitivity of 90% and a specificity of 88% and a positive predictive value of 90% in the test set. These suggest that SELDI-TOF-MS is an additional method for NTDs pregnancies detection. PMID:25054433

  6. Influence of honeybee sting on peptidome profile in human serum.

    PubMed

    Matysiak, Jan; Światły, Agata; Hajduk, Joanna; Matysiak, Joanna; Kokot, Zenon J

    2015-05-22

    The aim of this study was to explore the serum peptide profiles from honeybee stung and non-stung individuals. Two groups of serum samples obtained from 27 beekeepers were included in our study. The first group of samples was collected within 3 h after a bee sting (stung beekeepers), and the samples were collected from the same person a second time after at least six weeks after the last bee sting (non-stung beekeepers). Peptide profile spectra were determined using MALDI-TOF mass spectrometry combined with Omix, ZipTips and magnetic beads based on weak-cation exchange (MB-WCX) enrichment strategies in the mass range of 1-10 kDa. The samples were classified, and discriminative models were established by using the quick classifier, genetic algorithm and supervised neural network algorithms. All of the statistical algorithms used in this study allow distinguishing analyzed groups with high statistical significance, which confirms the influence of honeybee sting on the serum peptidome profile. The results of this study may broaden the understanding of the human organism's response to honeybee venom. Due to the fact that our pilot study was carried out on relatively small datasets, it is necessary to conduct further proteomic research of the response to honeybee sting on a larger group of samples.

  7. Microchip-based human serum atherogenic lipoprotein profile analysis.

    PubMed

    Wang, Hua; Zhang, Wei; Wan, Jun; Liu, Weiwei; Yu, Bo; Jin, Qinghui; Guan, Ming

    2014-12-15

    Owing to the mounting evidence of serum lipid changes in atherosclerosis, there has been increasing interest in developing new methods for analyzing atherogenic lipoprotein profiles. The separation of lipoprotein and lipoprotein subclasses has been demonstrated using a microchip capillary electrophoresis (CE) system [Chromatographia 74 (2011) 799-805]. In contrast to this previous study, the current report demonstrates that sdLDL peak efficiencies can be improved dramatically by adding gold nanoparticles (AuNPs) to the sample. Moreover, NBD C6-ceramide was identified as a satisfactory dye for specific labeling and quantitation of individual serum lipoproteins. The accuracy of the method was evaluated by comparison with ultracentrifuge separated small, dense, low-density lipoprotein (sdLDL). A high correlation was observed between these two methods for sdLDL cholesterol. Lipid levels were investigated between atherosclerotic patients and healthy controls. The variation of serum atherogenic lipoprotein profiles for atherosclerotic patients pre- and post-treatment was assessed by microchip CE. This method has potential for the rapid and sensitive detection of different lipoprotein classes as well as their subclasses and, therefore, is suitable for routine clinical applications. Microchip-based atherogenic lipoprotein profile assays will greatly improve the analysis of risk factors in atherosclerosis and will provide useful information for monitoring the effect of therapies on atherosclerotic disease.

  8. Evaluation of serum phosphopeptides as potential cancer biomarkers by mass spectrometric absolute quantification.

    PubMed

    Zhai, Guijin; Wu, Xiaoyan; Luo, Qun; Wu, Kui; Zhao, Yao; Liu, Jianan; Xiong, Shaoxiang; Feng, Yu-Qi; Yang, Liping; Wang, Fuyi

    2014-07-01

    Mass spectrometric quantification of phosphopeptides is a challenge due to the ion suppression effect of highly abundant non-phosphorylated peptides in complex samples such as serum. Several strategies for relative quantification of serum phosphopeptides based on MS have been developed, but the power of relative quantities was limited when making direct comparisons between two groups of samples or acting as a clinical examination index. Herein, we describe an MS absolute quantification strategy combined with Titania Coated Magnetic Hollow Mesoporous Silica Microspheres (TiO2/MHMSM) enrichment and stable isotopic acetyl labeling for phosphopeptides in human serum. Four endogenous serum phosphopeptides generated by degradation of fibrinogen were identified by LC-ESI-MS/MS following TiO2/MHMSM enrichment. The ESI-MS signal intensity ratios of the four phosphopeptide standards labeled with N-acetoxy-H3-succinimide (H3-NAS) and N-acetoxy-D3-succinimide (D3-NAS), following TiO2/MHMSM capture are linearly correlated with the molar ratios of the "light" to "heavy" phosphopeptides over the range of 0.1-4 with an r(2) of up to 0.998 and a slope of close to 1. The recovery of the four phosphopeptides spiked at low, medium and high levels in human sera were 98.4-111.9% with RSDs ranging 2.0-10.1%. The absolute quantification of the phosphopeptides in serum samples of 20 healthy persons and 20 gastric cancer patients by the developed method demonstrated that 3 out of the 4 phosphopeptides showed remarkable variation in serum level between healthy and cancer groups, and the phosphopeptide DpSGEGDFLAEGGGVR is significantly down-regulated in the serum of patients, being a potential biomarker for gastric cancer diagnosis. PMID:24840465

  9. Serum Metabolomic Profiling in Acute Alcoholic Hepatitis Identifies Multiple Dysregulated Pathways

    PubMed Central

    Rachakonda, Vikrant; Gabbert, Charles; Raina, Amit; Bell, Lauren N.; Cooper, Sara; Malik, Shahid; Behari, Jaideep

    2014-01-01

    Background and Objectives While animal studies have implicated derangements of global energy homeostasis in the pathogenesis of acute alcoholic hepatitis (AAH), the relevance of these findings to the development of human AAH remains unclear. Using global, unbiased serum metabolomics analysis, we sought to characterize alterations in metabolic pathways associated with severe AAH and identify potential biomarkers for disease prognosis. Methods This prospective, case-control study design included 25 patients with severe AAH and 25 ambulatory patients with alcoholic cirrhosis. Serum samples were collected within 24 hours of the index clinical encounter. Global, unbiased metabolomics profiling was performed. Patients were followed for 180 days after enrollment to determine survival. Results Levels of 234 biochemicals were altered in subjects with severe AAH. Random-forest analysis, principal component analysis, and integrated hierarchical clustering methods demonstrated that metabolomics profiles separated the two cohorts with 100% accuracy. Severe AAH was associated with enhanced triglyceride lipolysis, impaired mitochondrial fatty acid beta oxidation, and upregulated omega oxidation. Low levels of multiple lysolipids and related metabolites suggested decreased plasma membrane remodeling in severe AAH. While most measured bile acids were increased in severe AAH, low deoxycholate and glycodeoxycholate levels indicated intestinal dysbiosis. Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. Finally, altered levels of small molecules related to glutathione metabolism and antioxidant vitamin depletion were observed in patients with severe AAH. Univariable logistic regression revealed 15 metabolites associated with 180-day survival in severe AAH. Conclusion Severe AAH is

  10. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers

    PubMed Central

    Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P. V. L. N.; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

    2016-01-01

    Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient’s serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet’s serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10−6 in Fischer’s exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. PMID:26958841

  11. Prostate Cancer Associated Lipid Signatures in Serum Studied by ESI-Tandem Mass Spectrometryas Potential New Biomarkers.

    PubMed

    Duscharla, Divya; Bhumireddy, Sudarshana Reddy; Lakshetti, Sridhar; Pospisil, Heike; Murthy, P V L N; Walther, Reinhard; Sripadi, Prabhakar; Ummanni, Ramesh

    2016-01-01

    Prostate cancer (PCa) is one amongst the most common cancersin western men. Incidence rate ofPCa is on the rise worldwide. The present study deals with theserum lipidome profiling of patients diagnosed with PCa to identify potential new biomarkers. We employed ESI-MS/MS and GC-MS for identification of significantly altered lipids in cancer patient's serum compared to controls. Lipidomic data revealed 24 lipids are significantly altered in cancer patinet's serum (n = 18) compared to normal (n = 18) with no history of PCa. By using hierarchical clustering and principal component analysis (PCA) we could clearly separate cancer patients from control group. Correlation and partition analysis along with Formal Concept Analysis (FCA) have identified that PC (39:6) and FA (22:3) could classify samples with higher certainty. Both the lipids, PC (39:6) and FA (22:3) could influence the cataloging of patients with 100% sensitivity (all 18 control samples are classified correctly) and 77.7% specificity (of 18 tumor samples 4 samples are misclassified) with p-value of 1.612×10-6 in Fischer's exact test. Further, we performed GC-MS to denote fatty acids altered in PCa patients and found that alpha-linolenic acid (ALA) levels are altered in PCa. We also performed an in vitro proliferation assay to determine the effect of ALA in survival of classical human PCa cell lines LNCaP and PC3. We hereby report that the altered lipids PC (39:6) and FA (22:3) offer a new set of biomarkers in addition to the existing diagnostic tests that could significantly improve sensitivity and specificity in PCa diagnosis. PMID:26958841

  12. Impact of Serum and Plasma Matrices on the Titration of Human Inflammatory Biomarkers Using Analytically Validated SRM Assays.

    PubMed

    Dupin, Marilyne; Fortin, Tanguy; Larue-Triolet, Audrey; Surault, Isabelle; Beaulieu, Corinne; Gouel-Chéron, Aurélie; Allaouchiche, Bernard; Asehnoune, Karim; Roquilly, Antoine; Venet, Fabienne; Monneret, Guillaume; Lacoux, Xavier; Roitsch, Carolyn A; Pachot, Alexandre; Charrier, Jean-Philippe; Pons, Sylvie

    2016-08-01

    Protein biomarker discovery has inherent challenges linked to the validation of the analytical method used or to the impact of biological matrices. Matrix influences must be mastered to guarantee the reliability of the identified biomarkers to monitor human diseases. In this study, multiplexed mass spectrometry assays in selected reaction monitoring (SRM) mode have been developed to measure 107 inflammatory putative proteins in matched serum and plasma from 36 ICU trauma patients. The assays' validation directly in clinical samples was shown to be valuable to manage intersample variability. Using the validation process developed here, assays were validated for 58 biomarkers in serum, 57 in plasma, and 55 in both matrices. Correlation analyses demonstrated that the quantitation using SRM of most of the validated biomarkers (45/55) was impacted by the biological matrix and that the matrix impact was biomarker-dependent. Among the 45 impacted biomarkers, 23 were nevertheless correlated between serum and plasma, whereas the quantitation was shown to be equivalent in both for the 10 last proteins. Matrix selection using SRM is therefore suggested to be suitable prior to clinical evaluation of biomarkers in a large cohort of patients. PMID:27322794

  13. Serum cyclin-dependent kinase 9 is a potential biomarker of atherosclerotic inflammation

    PubMed Central

    Han, Yeming; Zhao, Shanshan; Gong, Yaoqin; Hou, Guihua

    2016-01-01

    Atherosclerotic coronary artery disease (CAD) is one of the most prevalent diseases worldwide. Atherosclerosis was considered to be the single most important contributor to CAD. In this study, a distinct serum protein expression pattern in CAD patients was demonstrated by proteomic analysis with two-dimensional gel electrophoresis coupled with mass spectrometry. In particular, CDK9 was found to be highly elevated in serum, monocytes and artery plaque samples of CAD patients. Furthermore, there was high infiltration of CD14+ monocytes/macrophages within artery plaques correlated with the expression of CDK9. Moreover, Flavopiridol (CDK9 inhibitor) could inhibit THP-1 cell (monocytic acute leukemia cell line) proliferation by targeting CDK9. Altogether, These findings indicate that CDK9 represent an important role for inflammation in the pathogenesis of atherosclerosis. It may be a potential biomarker of atherosclerotic inflammation and offer insights into the pathophysiology and targeted therapy for atherosclerotic CAD. PMID:26636538

  14. The Temporal Pattern of Changes in Serum Biomarker Levels Reveals Complex and Dynamically Changing Pathologies after Exposure to a Single Low-Intensity Blast in Mice

    PubMed Central

    Ahmed, Farid; Plantman, Stefan; Cernak, Ibolja; Agoston, Denes V.

    2015-01-01

    Time-dependent changes in blood-based protein biomarkers can help identify the ­pathological processes in blast-induced traumatic brain injury (bTBI), assess injury severity, and monitor disease progression. We obtained blood from control and injured mice (exposed to a single, low-intensity blast) at 2-h, 1-day, 1–week, and 1-month post-injury. We then determined the serum levels of biomarkers related to metabolism (4-HNE, HIF-1α, ceruloplasmin), vascular function (AQP1, AQP4, VEGF, vWF, Flk-1), inflammation (OPN, CINC1, fibrinogen, MIP-1a, OX-44, p38, MMP-8, MCP-1 CCR5, CRP, galectin-1), cell adhesion and the extracellular matrix (integrin α6, TIMP1, TIMP4, Ncad, connexin-43), and axonal (NF-H, Tau), neuronal (NSE, CK-BB) and glial damage (GFAP, S100β, MBP) at various post-injury time points. Our findings indicate that the exposure to a single, low-intensity blast results in metabolic and vascular changes, altered cell adhesion, and axonal and neuronal injury in the mouse model of bTBI. Interestingly, serum levels of several inflammatory and astroglial markers were either unchanged or elevated only during the acute and subacute phases of injury. Conversely, serum levels of the majority of biomarkers related to metabolic and vascular functions, cell adhesion, as well as neuronal and axonal damage remained elevated at the termination of the experiment (1 month), indicating long-term systemic and cerebral alterations due to blast. Our findings show that the exposure to a single, low-intensity blast induces complex pathological processes with distinct temporal profiles. Hence, monitoring serum biomarker levels at various post-injury time points may provide enhanced diagnostics in blast-related neurological and multi-system deficits. PMID:26124743

  15. Oral Fluids that Detect Cardiovascular Disease Biomarkers

    PubMed Central

    Foley, Joseph D.; Sneed, J. Darrell; Steinhubl, Steven R; Kolasa, Justin; Ebersole, Jeffrey L.; Lin, Yushun; Kryscio, Richard J.; McDevitt, John T.; Campbell, Charles L.; Miller, Craig S.

    2013-01-01

    Objective To determine the utility of oral fluids for assessment of coronary and cardiovascular (CVD) health. Study Design Twenty-nine patients with pre-existing CVD disease underwent an invasive cardiac procedure (alcohol septal ablation or percutaneous coronary intervention) and provided unstimulated whole saliva (UWS), sublingual swabs (LS), gingival swabs (GS) and serum at 0, 8, 16, 24, 48 hr. Concentrations of 13 relevant biomarkers were determined and correlated with levels in serum and the oral fluids. Results Concentrations of the majority of biomarkers were higher in UWS than LS and GS. Coronary and CVD disease biomarkers in UWS correlated better with serum than LS and GS based on group status and measures of time effect. Seven biomarkers demonstrated time effect changes consistent with serum biomarkers, including C-reactive protein and troponin I. Conclusions Changes in serum biomarker profiles are reflected in oral fluids suggesting that oral fluid biomarkers could aid in the assessment of cardiac ischemia/necrosis. PMID:22769406

  16. Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

    PubMed Central

    2014-01-01

    Background We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions Candidate proteins and mi

  17. Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

    SciTech Connect

    Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; Weitz, Karl K.; Morris, Michael J.; Skabelund, Andrew J.; Adkins, Joshua N.; Smith, Richard D.; Cho, Ji -Hoon; Gelinas, Richard

    2014-10-05

    Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbon monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins and mi

  18. Protein and microRNA biomarkers from lavage, urine, and serum in military personnel evaluated for dyspnea

    DOE PAGES

    Brown, Joseph N.; Brewer, Heather M.; Nicora, Carrie D.; Weitz, Karl K.; Morris, Michael J.; Skabelund, Andrew J.; Adkins, Joshua N.; Smith, Richard D.; Cho, Ji -Hoon; Gelinas, Richard

    2014-10-05

    Background: We have identified candidate protein and microRNA (miRNA) biomarkers for dyspnea by studying serum, lavage fluid, and urine from military personnel who reported serious respiratory symptoms after they were deployed to Iraq or Afghanistan. Methods: Forty-seven soldiers with the complaint of dyspnea who enrolled in the STudy of Active Duty Military Personnel for Environmental Dust Exposure (STAMPEDE) underwent comprehensive pulmonary evaluations at the San Antonio Military Medical Center. The evaluation included fiber-optic bronchoscopy with bronchoalveolar lavage. The clinical findings from the STAMPEDE subjects pointed to seven general underlying diagnoses or findings including airway hyperreactivity, asthma, low diffusivity of carbonmore » monoxide, and abnormal cell counts. The largest category was undiagnosed. As an exploratory study, not a classification study, we profiled proteins or miRNAs in lavage fluid, serum, or urine in this group to look for any underlying molecular patterns that might lead to biomarkers. Proteins in lavage fluid and urine were identified by accurate mass tag (database-driven) proteomics methods while miRNAs were profiled by a hybridization assay applied to serum, urine, and lavage fluid. Results: Over seventy differentially expressed proteins were reliably identified both from lavage and from urine in forty-eight dyspnea subjects compared to fifteen controls with no known lung disorder. Six of these proteins were detected both in urine and lavage. One group of subjects was distinguished from controls by expressing a characteristic group of proteins. A related group of dyspnea subjects expressed a unique group of miRNAs that included one miRNA that was differentially overexpressed in all three fluids studied. The levels of several miRNAs also showed modest but direct associations with several standard clinical measures of lung health such as forced vital capacity or gas exchange efficiency. Conclusions: Candidate proteins

  19. Post-Traumatic Hypoxia Is Associated with Prolonged Cerebral Cytokine Production, Higher Serum Biomarker Levels, and Poor Outcome in Patients with Severe Traumatic Brain Injury

    PubMed Central

    Yan, Edwin B.; Satgunaseelan, Laveniya; Paul, Eldho; Bye, Nicole; Nguyen, Phuong; Agyapomaa, Doreen; Kossmann, Thomas; Rosenfeld, Jeffrey V.

    2014-01-01

    Abstract Secondary hypoxia is a known contributor to adverse outcomes in patients with traumatic brain injury (TBI). Based on the evidence that hypoxia and TBI in isolation induce neuroinflammation, we investigated whether TBI combined with hypoxia enhances cerebral cytokine production. We also explored whether increased concentrations of injury biomarkers discriminate between hypoxic (Hx) and normoxic (Nx) patients, correlate to worse outcome, and depend on blood–brain barrier (BBB) dysfunction. Forty-two TBI patients with Glasgow Coma Scale ≤8 were recruited. Cerebrospinal fluid (CSF) and serum were collected over 6 days. Patients were divided into Hx (n=22) and Nx (n=20) groups. Eight cytokines were measured in the CSF; albumin, S100, myelin basic protein (MBP) and neuronal specific enolase (NSE) were quantified in serum. CSF/serum albumin quotient was calculated for BBB function. Glasgow Outcome Scale Extended (GOSE) was assessed at 6 months post-TBI. Production of granulocye macrophage-colony stimulating factor (GM-CSF) was higher, and profiles of GM-CSF, interferon (IFN)-γ and, to a lesser extent, tumor necrosis factor (TNF), were prolonged in the CSF of Hx but not Nx patients at 4–5 days post-TBI. Interleukin (IL)-2, IL-4, IL-6, and IL-10 increased similarly in both Hx and Nx groups. S100, MBP, and NSE were significantly higher in Hx patients with unfavorable outcome. Among these three biomarkers, S100 showed the strongest correlations to GOSE after TBI-Hx. Elevated CSF/serum albumin quotients lasted for 5 days post-TBI and displayed similar profiles in Hx and Nx patients. We demonstrate for the first time that post-TBI hypoxia is associated with prolonged neuroinflammation, amplified extravasation of biomarkers, and poor outcome. S100 and MBP could be implemented to track the occurrence of post-TBI hypoxia, and prompt adequate treatment. PMID:24279428

  20. Serum SP-D levels as a biomarker of lung injury in children suffering of bronchopneumonia.

    PubMed

    Mosbah, Amira A Abd El-rahman; Abdellatif, Nahla A Bahgat; Sorour, Ehab Ibrahim; Awadallah, Mohamed Fawzy M

    2012-04-01

    The efficacy of SP-D concentration as a useful biomarker of the severity of lung injury in children with bronchopneumonia with or without chronic airway disease was studied. A total of 48 patients (2 to 4 years old) diagnosed bronchopneumonia were admitted to Department of Pediatrics, Al-Dar hospital, Al-Madinah, Saudi Arabia over the year 2009. They were divided into two groups: G1 included patients without any underlying disease and G2 included asthmatic patients. They were assigned to one of three categories. Stage A patients without oxygen dosage, Stage B patients required oxygen dosage, and Stage C patients required ICU admission. We evaluated baseline characteristics, clinical features, and serum SP-D concentration in G1, G2, and G3a (healthy control cross-matched infants). The mean serum SP-D concentrations in G1 and G2 were higher than those in G3 (118.7 +/- 46.2 & 39.7 +/- 18.7 ng/ml, respectively), but also higher in G2 than in G1 (149.9 +/- 52.8 & 109.8 + 36.7 ng/ml, respectively). The mean serum SP-D concentrations were higher in Stage C than in Stages A or B patients, and mean serum SP-D concentrations were higher in Stage B than in Stage A. PMID:22662592

  1. Trefoil factor family (TFF) proteins as potential serum biomarkers in patients with metastatic colorectal cancer.

    PubMed

    Vocka, M; Langer, D; Petrtyl, J; Vockova, P; Hanus, T; Kalousova, M; Zima, T; Petruzelka, L

    2015-01-01

    Trefoil factor family (TFF) is composed of three secretory proteins (TFF1, TFF2 and TFF3) that play an important role in mucosal protection of gastrointestinal tract. Their overexpression in colorectal tumors seems to be associated with more aggressive disease. We collected serum samples from 79 healthy controls and 97 patients with metastatic colorectal cancer at the time of diagnosis or at progression. Serum levels of TTF1-3, CEA and CA19-9 were measured by ELISA. Serum TFF1 and TFF3 levels were significantly higher in patients with colorectal cancer compared to healthy controls (p < 0.0001). Moreover, serum levels of TFF3 correlated with extent of liver involvement in patient without pulmonary metastases and patients with higher TFF3 levels had significantly worse outcome (p < 0.0001). Compared to CEA and CA19-9, TFF3 had higher sensitivity and the same specificity. Our results indicate that TFF3 is an effective biomarker in patients with metastatic colorectal cancer with higher sensitivity than CEA a CA19-9. TFF3 levels strongly correlate with extension of liver disease and seem to have prognostic value.

  2. Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis

    PubMed Central

    Maekawa, Tomohiro; Kamada, Yoshihiro; Ebisutani, Yusuke; Ueda, Makiko; Hata, Tomoki; Kawamoto, Koichi; Takamatsu, Shinji; Mizutani, Kayo; Shimomura, Mayuka; Sobajima, Tomoaki; Fujii, Hironobu; Nakayama, Kotarosumitomo; Nishino, Kimihiro; Yamada, Makoto; Kumada, Takashi; Ito, Toshifumi; Eguchi, Hidetoshi; Nagano, Hiroaki; Miyoshi, Eiji

    2016-01-01

    AIM: To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis. METHODS: Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer (including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay (carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic (ROC) analyses. RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp. CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population. PMID:27158210

  3. Serum Phenylalanine, Tyrosine, and their Ratio in Acute Ischemic Stroke: on the Trail of a Biomarker?

    PubMed

    Ormstad, Heidi; Verkerk, Robert; Sandvik, Leiv

    2016-01-01

    Fast diagnosis and appropriate treatment are of utmost importance to improving the outcome in patients with acute ischemic stroke (AIS). A rapid and sensitive blood test for ischemic stroke is required. The aim of this study was to examine the usefulness of phenylalanine (PHE) and tyrosine (TYR) as diagnostic biomarkers in AIS. Serum levels of PHE and TYR, measured using HPLC, and their ratio (PHE/TYR) were compared between 45 patients with AIS and 40 healthy control subjects. The relationship between PHE/TYR and the serum levels of several cytokines were also examined. PHE/TYR was significantly higher in AIS patients than in healthy controls (1.75 vs 1.24, p < 0.001). A receiver operating characteristic (ROC) curve analysis of PHE/TYR in AIS patients relative to healthy controls revealed promising sensitivity and specificity, which at an optimal cutoff of 1.45 were 76 and 85 %, respectively. PHE/TYR was positively correlated with interleukin (IL)-1β (r = 0.37, p = 0.011) and IL-6 (r = 0.33, p = 0.025). This study shows that PHE/TYR is highly elevated in the acute phase of AIS, and that this elevation is coupled to the inflammatory response. The ROC analysis documents the possible value of PHE/TYR as a biomarker for AIS and demonstrates its clinical potential as a blood-based test for AIS.

  4. Serum miRNAs as predictive and preventive biomarker for pre-clinical hepatocellular carcinoma.

    PubMed

    Li, Liang; Chen, Jianguo; Chen, Xin; Tang, Jing; Guo, Huan; Wang, Xiaofeng; Qian, Ji; Luo, Guijuan; He, Fangping; Lu, Xiaomei; Ding, Yibo; Yang, Yingchen; Huang, Wentao; Hou, Guojun; Lin, Ximeng; Ouyang, Qin; Li, Hengyu; Wang, Ruoyu; Jiang, Feng; Pu, Rui; Lu, Jianhua; Jin, Mudan; Tan, Yexiong; Gonzalez, Frank J; Cao, Guangwen; Wu, Mengchao; Wen, Hao; Wu, Tangchun; Jin, Li; Chen, Lei; Wang, Hongyang

    2016-04-10

    The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6-12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using α-fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations. PMID:26850373

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

    PubMed Central

    Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco

    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 architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout 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 is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers. PMID:26536916

  6. Serum Exosome MicroRNA as a Minimally-Invasive Early Biomarker of AML

    PubMed Central

    Hornick, Noah I.; Huan, Jianya; Doron, Ben; Goloviznina, Natalya A.; Lapidus, Jodi; Chang, Bill H.; Kurre, Peter

    2015-01-01

    Relapse remains the major cause of mortality for patients with Acute Myeloid Leukemia (AML). Improved tracking of minimal residual disease (MRD) holds the promise of timely treatment adjustments to preempt relapse. Current surveillance techniques detect circulating blasts that coincide with advanced disease and poorly reflect MRD during early relapse. Here, we investigate exosomes as a minimally invasive platform for a microRNA (miRNA) biomarker. We identify a set of miRNA enriched in AML exosomes and track levels of circulating exosome miRNA that distinguish leukemic xenografts from both non-engrafted and human CD34+ controls. We develop biostatistical models that reveal circulating exosomal miRNA at low marrow tumor burden and before circulating blasts can be detected. Remarkably, both leukemic blasts and marrow stroma contribute to serum exosome miRNA. We propose development of serum exosome miRNA as a platform for a novel, sensitive compartment biomarker for prospective tracking and early detection of AML recurrence. PMID:26067326

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

    NASA Astrophysics Data System (ADS)

    Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A.; Hansen, Mikkel F.; Ranzoni, Andrea; Donolato, Marco

    2015-11-01

    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 architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout 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 is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers.

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

    PubMed

    Antunes, Paula; Watterson, Daniel; Parmvi, Mattias; Burger, Robert; Boisen, Anja; Young, Paul; Cooper, Matthew A; Hansen, Mikkel F; Ranzoni, Andrea; Donolato, Marco

    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 architecture. The presence of the target antigen NS1 triggers MNP agglutination and the formation of nanoclusters with rapid kinetics enhanced by external magnetic actuation. The amount and size of the nanoclusters correlate with the target concentration and can be quantified using an optomagnetic readout 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 is implemented on a low-cost microfluidic disc the platform is suited for further expansion to multiplexed detection of a wide panel of biomarkers. PMID:26536916

  9. Serum microRNA biomarkers for detection of non-small cell lung cancer.

    PubMed

    Hennessey, Patrick T; Sanford, Tiffany; Choudhary, Ashish; Mydlarz, Wojciech W; Brown, David; Adai, Alex Tamas; Ochs, Michael F; Ahrendt, Steven A; Mambo, Elizabeth; Califano, Joseph A

    2012-01-01

    Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73-0.91), sensitivity of 100% (95% CI; 0.93-1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results.

  10. Serum microRNA Biomarkers for Detection of Non-Small Cell Lung Cancer

    PubMed Central

    Hennessey, Patrick T.; Sanford, Tiffany; Choudhary, Ashish; Mydlarz, Wojciech W.; Brown, David; Adai, Alex Tamas; Ochs, Michael F.; Ahrendt, Steven A.; Mambo, Elizabeth; Califano, Joseph A.

    2012-01-01

    Non small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality world-wide and the majority of cases are diagnosed at late stages of disease. There is currently no cost-effective screening test for NSCLC, and the development of such a test is a public health imperative. Recent studies have suggested that chest computed tomography screening of patients at high risk of lung cancer can increase survival from disease, however, the cost effectiveness of such screening has not been established. In this Phase I/II biomarker study we examined the feasibility of using serum miRNA as biomarkers of NSCLC using RT-qPCR to examine the expression of 180 miRNAs in sera from 30 treatment naive NSCLC patients and 20 healthy controls. Receiver operating characteristic curves (ROC) and area under the curve were used to identify differentially expressed miRNA pairs that could distinguish NSCLC from healthy controls. Selected miRNA candidates were further validated in sera from an additional 55 NSCLC patients and 75 healthy controls. Examination of miRNA expression levels in serum from a multi-institutional cohort of 50 subjects (30 NSCLC patients and 20 healthy controls) identified differentially expressed miRNAs. A combination of two differentially expressed miRNAs miR-15b and miR-27b, was able to discriminate NSCLC from healthy controls with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100% in the training set. Upon further testing on additional 130 subjects (55 NSCLC and 75 healthy controls), this miRNA pair predicted NSCLC with a specificity of 84% (95% CI 0.73–0.91), sensitivity of 100% (95% CI; 0.93–1.0), NPV of 100%, and PPV of 82%. These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of NSCLC. Further testing in a Phase III biomarker study in is necessary for validation of these results. PMID:22389695

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

    PubMed Central

    Armah, Henry B; Wilson, Nana O; Sarfo, Bismark Y; Powell, Michael D; Bond, Vincent C; Anderson, Winston; Adjei, Andrew A; Gyasi, Richard K; Tettey, Yao; Wiredu, Edwin K; Tongren, Jon Eric; Udhayakumar, Venkatachalam; Stiles, Jonathan K

    2007-01-01

    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 mortality in CM

  12. Detection of glyco-mucin profiles improves specificity of MUC16 and MUC1 biomarkers in ovarian serous tumours.

    PubMed

    Ricardo, Sara; Marcos-Silva, Lara; Pereira, Daniela; Pinto, Rita; Almeida, Raquel; Söderberg, Ola; Mandel, Ulla; Clausen, Henrik; Felix, Ana; Lunet, Nuno; David, Leonor

    2015-02-01

    The CA125 assay detects circulating MUC16 and is one of the most widely used cancer biomarkers for the follow-up of ovarian cancer. We previously demonstrated that detection of aberrant cancer-associated glycoforms of MUC16 as well as MUC1 in circulation could improve the yield of these serum assays. Our aim was to refine ovarian cancer biomarkers by detection of aberrant glycoforms (Tn, STn, and T) of MUC16 and MUC1 in ovarian cancer tissue using Proximity Ligation Assays (PLA). We studied two series of serous ovarian tumours, a pilot series of 66 ovarian tumours (27 cystadenomas, 16 borderline tumours and 23 adenocarcinomas) from Centro Hospitalar S. João, Porto and a validation series of 89 ovarian tumours (17 cystadenomas, 25 borderline tumours and 47 adenocarcinomas) from the Portuguese Institute of Oncology Francisco Gentil, Lisbon. PLA reactions for MUC16/Tn, MUC16/STn, MUC1/Tn and MUC1/STn were negative in benign lesions but often positive in borderline and malignant lesions, in both series. An even better yield was obtained based on positivity for any of the four glyco-mucin profiles, further increasing sensitivity to 72% and 83% in the two series, respectively, with 100% specificity. The strategy is designated glyco-mucin profiling and provides strong support for development of PLA-based serum assays for early diagnosis.

  13. Combined Serum Biomarkers in Non-Invasive Diagnosis of Non-Alcoholic Steatohepatitis

    PubMed Central

    Liu, Yuan; Guo, Xiaodong; Li, Wenshu; Guo, Chaonan; Zhang, Hongping; Gao, Yinjie; Mao, Yuanli; Zhao, Jingmin

    2015-01-01

    Background Non-alcoholic steatoheaptitis (NASH), the critical stage of non-alcoholic fatty liver disease (NAFLD), is of chronic progression and can develop cirrhosis even hepatocellular carcinoma (HCC). However, non-invasive biomarkers for NASH diagnosis remain poorly applied in clinical practice. Our study aims at testing the accuracy of the combination of cytokeratin-18 M30 fragment (CK-18-M30), fibroblast growth factor 21 (FGF-21), interleukin 1 receptor antagonist (IL-1Ra), pigment epithelium-derived factor (PEDF) and osteoprotegerin (OPG) in diagnosing NAFLD and NASH. Methods 179 patients with biopsy-proven NAFLD were enrolled as training group, 91 age- and gender-matched healthy subjects were recruited at the same time as controls. 63 other NAFLD patients were separately collected as validation group. 45 alcoholic fatty liver disease (AFLD) patients, 50 hepatitis B virus (HBV) patients, 52 hepatitis C virus (HCV) patients were also included. Serum biomarker levels were measured by enzyme-linked immunosorbent assay. Results Serum levels of CK-18-M30, FGF-21, IL-1Ra and PEDF increased, while OPG decreased in a stepwise fashion in controls, non-NASH NAFLD patients and NASH patients (P < 0.01). The area under receiver-operating characteristics curve to diagnose NASH was 0.86 for CK-18-M30, 0.89 for FGF-21, 0.89 for IL-1Ra, 0.89 for PEDF and 0.89 for OPG. CK-18-M30 had 70% negative predictive value (NPV) and 79% positive predictive value (PPV) to diagnose NASH. A 5-step approach measuring CK-18-M30 followed by FGF21, IL-1Ra, PEDF and OPG gradually improved the NPV to 76% and PPV to 85%, which reached 80% and 76% respectively in the validation cohort. Conclusion Compared to single biomarker, stepwise combination of CK-18-M30, FGF-21, IL-1Ra, PEDF and OPG can further improve the accuracy in diagnosing NASH. PMID:26121037

  14. Serum cell death biomarkers for prediction of liver fibrosis and poor prognosis in primary biliary cirrhosis.

    PubMed

    Sekiguchi, Tomohiro; Umemura, Takeji; Fujimori, Naoyuki; Shibata, Soichiro; Ichikawa, Yuki; Kimura, Takefumi; Joshita, Satoru; Komatsu, Michiharu; Matsumoto, Akihiro; Tanaka, Eiji; Ota, Masao

    2015-01-01

    The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

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

    PubMed

    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. Serum protein profile of Crohn's disease treated with infliximab.

    PubMed

    Gazouli, Maria; Anagnostopoulos, Athanasios K; Papadopoulou, Aggeliki; Vaiopoulou, Anna; Papamichael, Konstantinos; Mantzaris, Gerassimos; Theodoropoulos, George E; Anagnou, Nicholas P; Tsangaris, George Th

    2013-11-01

    The infliximab (IFX) has dramatically improved the treatment of Crohn's disease (CD). However, the need for predictive factors, indicative of patients' response to IFX, has yet to be met. In the current study, proteomics technologies were employed in order to monitor for differences in protein expression in a cohort of patients following IFX administration, aiming at identifying a panel of candidate protein biomarkers of CD, symptomatic of response to treatment. We enrolled 18 patients, who either had achieved clinical and serological remission (Rm, n=6), or response (Rs, n=6) and/or were PNRs (n=6), to IFX. Serum samples were subjected to two-dimensional Gel Electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by MALDI-TOF-MS. Identified proteins where evaluated by immunoblot analysis while functional network association was carried out to asses significance. Proteins apolipoprotein A-I (APOA1), apolipoprotein E (APOE), complement C4-B (CO4B), plasminogen (PLMN), serotransferrin (TRFE), beta-2-glycoprotein 1 (APOH), and clusterin (CLUS) were found to be up-regulated in the PNR and Rs groups whereas their levels displayed no changes in the Rm group when compared to baseline samples. Additionally, leucine-rich alpha-2-glycoprotein (A2GL), vitamin D-binding protein (VTDB), alpha-1B-glycoprotein (A1BG) and complement C1r subcomponent (C1R) were significantly increased in the serum of the Rm group. Through the incorporation of proteomics technologies, novel serum marker-molecules demonstrating high sensitivity and specificity are introduced, hence offering an innovative approach regarding the evaluation of CD patients' response to IFX therapy.

  17. SELDI-TOF derived serum biomarkers failed to differentiate between patients with beryllium sensitisation and patients with chronic beryllium disease

    PubMed Central

    Tooker, B C; Bowler, R P; Orcutt, J M; Maier, L A; Christensen, H M; Newman, L S

    2015-01-01

    Background People exposed to beryllium may develop beryllium sensitisation (BeS) and, in some cases, progress to chronic beryllium disease (CBD). Objectives The objective of this study was to test the ability of proteomic technology to identify patterns of serum protein biomarkers that allow differentiation between BeS and CBD and thus remove the need for invasive bronchoscopic procedures. Methods Initially, SELDI-TOF methodology and analysis was performed on serum samples from 30 CBD and 31 BeS patients. Results This ‘starter set’ yielded two distinct biomarker pattern sets with eight candidate proteins. The first set differentiated between BeS and CBD with 83.3% sensitivity and 82.3% specificity, with 10-fold cross-validation of 75% and 79%, respectively. The second set of biomarkers yielded higher sensitivity (90.0%) and higher specificity (90.3%), with 10-fold cross-validation of 71.7% and 82.3%, respectively. Due to its greater sensitivity and specificity, the second set of biomarkers was used as the framework for differentiating between CBD and BeS in a second set of serum samples from 450 patients with BeS and CBD. When this larger set of samples was subjected to the biomarker framework in a blinded fashion, it yielded a sensitivity of 43.53% and a specificity of 38.93%. Conclusions Due to these low sensitivity and specificity values, we have concluded that, currently, the unique set of SELDI-TOF derived biomarkers does not possess the qualities that would allow it to differentiate between a CBD patient and a BeS patient using serum protein biomarkers. Future refinements in sample collection or proteomic technology may be needed to improve biomarker discovery. PMID:21278142

  18. Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes.

    PubMed

    Mehta, Nishaki; Chacko, Paul; Jin, James; Tran, Tam; Prior, Thomas W; He, Xin; Agarwal, Gunjan; Raman, Subha V

    2016-08-01

    Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy. PMID:27547137

  19. Serum versus Imaging Biomarkers in Friedreich Ataxia to Indicate Left Ventricular Remodeling and Outcomes

    PubMed Central

    Chacko, Paul; Jin, James; Tran, Tam; Prior, Thomas W.; He, Xin; Agarwal, Gunjan; Raman, Subha V.

    2016-01-01

    Patients with Friedreich ataxia typically die of cardiomyopathy, marked by myocardial fibrosis and abnormal left ventricular (LV) geometry. We measured procollagen I carboxyterminal propeptide (PICP), a serum biomarker of collagen production, and characterized genotypes, phenotypes, and outcomes in these patients. Twenty-nine patients with Friedreich ataxia (mean age, 34.2 ± 2.2 yr) and 29 healthy subjects (mean age, 32.5 ± 1.1 yr) underwent serum PICP measurements. Patients underwent cardiac magnetic resonance imaging and outcome evaluations at baseline and 12 months. Baseline PICP values were significantly higher in the patients than in the control group (1,048 ± 77 vs 614 ± 23 ng/mL; P <0.001); severity of genetic abnormality did not indicate severity of PICP elevation. Higher PICP levels corresponded to greater LV concentric remodeling only at baseline (r=0.37, P <0.05). Higher baseline PICP strongly indicated subsequent increases in LV end-diastolic volume (r=0.52, P=0.02). The PICP levels did not distinguish between 14 patients with evident myocardial fibrosis identified through positive late gadolinium enhancement and 15 who had no enhancement (1,067 ± 125 vs 1,030 ± 98 ng/mL; P=0.82). At 12 months, cardiac events had occurred in 3 of 14 fibrosis-positive and none of 15 fibrosis-negative patients (P=0.1); their baseline PICP levels were similar. We conclude that PICP, a serum marker of collagen synthesis, is elevated in Friedreich ataxia and indicates baseline abnormal LV geometry and subsequent dilation. Cardiac magnetic resonance and PICP warrant consideration as complementary biomarkers in therapeutic trials of Friedreich ataxia cardiomyopathy. PMID:27547137

  20. PiB-PET Imaging-Based Serum Proteome Profiles Predict Mild Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Kang, Seokjo; Jeong, Hyobin; Baek, Je-Hyun; Lee, Seung-Jin; Han, Sun-Ho; Cho, Hyun Jin; Kim, Hee; Hong, Hyun Seok; Kim, Young Ho; Yi, Eugene C; Seo, Sang Won; Na, Duk L; Hwang, Daehee; Mook-Jung, Inhee

    2016-07-01

    Development of a simple, non-invasive early diagnosis platform of Alzheimer's disease (AD) using blood is urgently required. Recently, PiB-PET imaging has been shown to be powerful to quantify amyloid-β plaque loads leading to pathophysiological alterations in AD brains. Thus, there has been a need for serum biomarkers reflecting PiB-PET imaging data as an early diagnosis platform of AD. Here, using LC-MS/MS analysis coupled with isobaric tagging, we performed comprehensive proteome profiling of serum samples from cognitively normal controls, mild cognitive impairment (MCI), and AD patients, who were selected using PiB-PET imaging. Comparative analysis of the proteomes revealed 79 and 72 differentially expressed proteins in MCI and AD, respectively, compared to controls. Integrated analysis of these proteins with genomic and proteomic data of AD brain tissues, together with network analysis, identified three biomarker candidates representing the altered proteolysis-related process in MCI or AD: proprotein convertase subtilisin/kexin type 9 (PCSK9), coagulation factor XIII, A1 polypeptide (F13A1), and dermcidin (DCD). In independent serum samples of MCI and AD, we confirmed the elevation of the candidates using western blotting and ELISA. Our results suggest that these biomarker candidates can serve as a potential non-invasive early diagnosis platform reflecting PiB-PET imaging for MCI and AD. PMID:27392853

  1. Serum Calcium Increase Correlates With Worsening of Lipid Profile

    PubMed Central

    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

  2. Serum YKL-40: a potential biomarker for psoriasis or endothelial dysfunction in psoriasis?

    PubMed

    Erfan, Gamze; Guzel, Savas; Alpsoy, Seref; Rifaioglu, Emine N; Kaya, Sule; Kucukyalcın, Volkan; Topcu, Birol; Kulac, Mustafa

    2015-02-01

    Psoriasis is a disease that can contribute to a risk of atherosclerosis. In several studies, impaired endothelial dysfunction (ED) is correlated with psoriasis. Serum YKL-40 is a new inflammatory biomarker of vascular damage, like ED and cardiovascular diseases. The aim of the study was to compare relevance of serum YKL-40 levels in psoriasis patients and healthy subjects according to ED diagnosis and identifiable cardiovascular risk factors. Sixty (31 female, 29 male) patients with plaque psoriasis, and 30 (18 female, 12 male) healthy controls were selected according to whether they had at least one or no identifiable risk factors for cardiovascular disease. All subjects were evaluated ultrasonographically for endothelial function and diagnosed as with or without ED and all groups compared for serum YKL-40 levels. YKL-40 levels of psoriatic patients with ED were higher than healthy controls with ED (P = <0.05). There were no statistical differences in between subjects without ED. YKL-40 levels of patients over age of 40 were higher than younger ones (P < 0.05). But in healthy controls, there were no differences. In comparison of cardiovascular risk-positive (RP) patients and RP healthy subjects, YKL-40 levels were higher in RP patients (P = <0.05). The elevation of plasma YKL-40 in psoriasis can be associated not only with inflammation of the disease, but also with ED. YKL-40 can be used as a marker for predicting and preventing cardiovascular diseases in RP psoriatic patients with age above 40.

  3. Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats.

    PubMed

    Kim, Ji-Eun; Lee, Young-Ju; Kwak, Moon-Hwa; Jun, Go; Koh, Eun-Kyoung; Song, Sung-Hwa; Seong, Ji-Eun; Kim, Ji Won; Kim, Kyu-Bong; Kim, Suhkmann; Hwang, Dae-Youn

    2014-03-01

    Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using (1)H nuclear magnetic resonance ((1)H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the No-treated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the No-treated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation. PMID:24707303

  4. Metabolomics approach to serum biomarker for loperamide-induced constipation in SD rats

    PubMed Central

    Kim, Ji-Eun; Lee, Young-Ju; Kwak, Moon-Hwa; Jun, Go; Koh, Eun-Kyoung; Song, Sung-Hwa; Seong, Ji-Eun; Kim, Ji Won; Kim, Kyu-Bong; Kim, Suhkmann

    2014-01-01

    Loperamide has long been known as an opioid-receptor agonist useful as a drug for treatment of diarrhea resulting from gastroenteritis or inflammatory bowel disease as well as to induce constipation. To determine and characterize putative biomarkers that can predict constipation induced by loperamide treatment, alteration of endogenous metabolites was measured in the serum of Sprague Dawley (SD) rats treated with loperamide for 3 days using 1H nuclear magnetic resonance (1H NMR) spectral data. The amounts and weights of stool and urine excretion were significantly lower in the loperamide-treated group than the No-treated group, while the thickness of the villus, crypt layer, and muscle layer was decreased in the transverse colon of the same group. The concentrations of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatinine (Cr) were also slightly changed in the loperamide-treated group, although most of the serum components were maintained at a constant level. Furthermore, pattern recognition of endogenous metabolites showed completely separate clustering of the serum analysis parameters between the No-treated group and loperamide-treated group. Among 35 endogenous metabolites, four amino acids (alanine, glutamate, glutamine and glycine) and six endogenous metabolites (acetate, glucose, glycerol, lactate, succinate and taurine) were dramatically decreased in loperamide-treated SD rats. These results provide the first data pertaining to metabolic changes in SD rats with loperamide-induced constipation. Additionally, these findings correlate the changes in 10 metabolites with constipation. PMID:24707303

  5. Clinical, microbiological, and salivary biomarker profiles of dental implant patients with type 2 Diabetes

    PubMed Central

    Tatarakis, Nikolaos; Kinney, Janet S.; Inglehart, Marita; Braun, Thomas M.; Shelburne, Charles; Lang, Niklaus P.; Giannobile, William V.; Oh, Tae-Ju

    2015-01-01

    Objective Regulators of peri-implant bone loss in diabetic patients appears to involve multiple risk factors that have not been clearly elucidated. This study was conducted to explore putative local etiologic factors on implant bone loss in relation to type 2 diabetes mellitus, including clinical, microbial, salivary biomarker, and psychosocial factors. Materials and Methods Thirty-two subjects (divided into type 2 diabetes mellitus and non-diabetic controls), having at least one functional implant and 6 teeth, were enrolled in a one-year longitudinal investigation. Analyses of clinical measurements and standardized intra-oral radiographs, saliva and serum biomarkers (via protein arrays for 20 selected markers) and plaque biofilm (via qPCR for 8 periodontal pathogens) were performed at baseline and 1 year. In addition, the subjects were asked to respond to questionnaires to assess behavioral and psychosocial variables. Results There was a significant increase from baseline to 1 year in the probing depth of implants in the diabetes group (1.95mm to 2.35mm, p=0.015). The average radiographic bone loss during the study period marginally increased at dental implants compared to natural teeth over the study period (0.08mm vs. 0.05mm; p=0.043). The control group harbored higher levels of T. denticola at their teeth at baseline (p=0.046) and the levels of the pathogen increased significantly over time around the implants of the same group (p=0.003). Salivary osteoprotegerin (OPG) levels were higher in the diabetes group than the control group at baseline only; in addition, the salivary levels of IL-4, IL-10, and OPG associated with host defense were significantly reduced in the diabetes group (p=0.010, p=0.019, and p=0.024) while controls showed an increase in the salivary OPG levels (p=0.005). For psychosocial factors, there were not many significant changes over the observation period, except for some findings related to coping behaviors at baseline. Conclusions The

  6. Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke

    PubMed Central

    Li, Qian; Lin, Yuanshao; Huang, Wensi; Zhou, Yulei; Chen, Xiaoli; Wang, Brian; Zhang, Wanli; Cai, Zhengyi; Xue, Jie; Zhang, Wenhui; Yu, Tieer; Wang, Hong; He, Jincai; Jin, Kunlin; Shao, Bei

    2016-01-01

    Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS. PMID:27699084

  7. Serum IL-33 Is a Novel Diagnostic and Prognostic Biomarker in Acute Ischemic Stroke

    PubMed Central

    Qian, Li; Yuanshao, Lin; Wensi, Huang; Yulei, Zhou; Xiaoli, Chen; Brian, Wang; Wanli, Zhang; Zhengyi, Cai; Jie, Xue; Wenhui, Zhang; Tieer, Yu; Hong, Wang; Jincai, He; Kunlin, Jin; Bei, Shao

    2016-01-01

    Interleukin-33 (IL-33), a newly recognized IL-1 family member, is expressed in various tissues and cells, and involved in pathogenesis of many human diseases. For example, IL-33 plays a protective role in cardiovascular diseases. However, the role of IL-33 in acute ischemic stroke (AIS) remains unclear. This study aims to investigate whether IL-33 level in AIS patient serum can be used as a potential diagnostic and prognostic marker. The study included two hundred and six patients with first-ever ischemic stroke, who were admitted within 72 hours after stroke onset. The serum level of IL-33 was measured with ELISA and the severity of AIS patients on admission was evaluated based on the National Institutes of Health Stroke Scale (NIHSS) score. The functional outcome at 3 months was determined using the Barthel index (BI). We found that serum IL-33 was significantly higher (P < 0.001) in patients with AIS [57.68 ng/L (IQR, 44.95-76.73)] compared with healthy controls [47.48 ng/L (IQR, 38.67-53.78)]. IL-33 was an independent diagnostic biomarker for AIS with an OR of 1.051 (95%Cl, 1.018-1.085; P=0.002). Serum IL-33 was higher (P < 0.05) in the stroke patients with small cerebral infarction volume compared to AIS patients with large cerebral infarction. In addition, serum IL-33 was also significantly higher (P = 0.001) in the patients with mild stroke, compared to the patients with severe stroke. Furthermore, serum IL-33 level in AIS patients with a worse outcome was higher (P < 0.001) compared to AIS patients with a better outcome. IL-33 was also an independent predictor for the functional outcome with an adjusted OR of 0.932 (95% CI, 0.882-0.986). Our results suggest that the lower level of serum IL-33 is associated with large infarction volume and greater stroke severity in AIS patients. Thus, IL-33 can be used as a novel and independent diagnostic and predicting prognostic marker in AIS.

  8. Elevated baseline serum glutamate as a pharmacometabolomic biomarker for acamprosate treatment outcome in alcohol-dependent subjects

    PubMed Central

    Nam, H W; Karpyak, V M; Hinton, D J; Geske, J R; Ho, A M C; Prieto, M L; Biernacka, J M; Frye, M A; Weinshilboum, R M; Choi, D-S

    2015-01-01

    Acamprosate has been widely used since the Food and Drug Administration approved the medication for treatment of alcohol use disorders (AUDs) in 2004. Although the detailed molecular mechanism of acamprosate remains unclear, it has been largely known that acamprosate inhibits glutamate action in the brain. However, AUD is a complex and heterogeneous disorder. Thus, biomarkers are required to prescribe this medication to patients who will have the highest likelihood of responding positively. To identify pharmacometabolomic biomarkers of acamprosate response, we utilized serum samples from 120 alcohol-dependent subjects, including 71 responders (maintained continuous abstinence) and 49 non-responders (any alcohol use) during 12 weeks of acamprosate treatment. Notably, baseline serum glutamate levels were significantly higher in responders compared with non-responders. Importantly, serum glutamate levels of responders are normalized after acamprosate treatment, whereas there was no significant glutamate change in non-responders. Subsequent functional studies in animal models revealed that, in the absence of alcohol, acamprosate activates glutamine synthetase, which synthesizes glutamine from glutamate and ammonia. These results suggest that acamprosate reduces serum glutamate levels for those who have elevated baseline serum glutamate levels among responders. Taken together, our findings demonstrate that elevated baseline serum glutamate levels are a potential biomarker associated with positive acamprosate response, which is an important step towards development of a personalized approach to treatment for AUD. PMID:26285131

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

    PubMed

    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 < 0.05) between the ovarian cancer and healthy control. According to the receiver operating characteristic curve analysis, arabitol was the most potentially specific biomarker for discriminating ovarian cancer from healthy control, having an area under the curve of 0.911. A panel of metabolite markers composed of maltose, maltotriose, raffinose, and mannitol was selected, which was able to discriminate the ovarian cancer from the benign ovarian tumor counterparts, with an area under concentration-time curve value of 0.832. Endogenous carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer.

  10. Serum Levels of Interleukin-6 and Interleukin-10 as Biomarkers for Hepatocellular Carcinoma in Egyptian Patients.

    PubMed

    Othman, Mohamed S; Aref, Ahmed M; Mohamed, Amal A; Ibrahim, Wesam A

    2013-01-01

    Interleukin-10 (IL-10) and interleukin-6 (IL-6) have been reported to be related to hepatocellular carcinoma (HCC) prognosis. This study aimed to investigate the clinical usefulness of serum levels of IL-6 and IL-10 as biomarkers for HCC among high-risk patients. Materials and Methods. 80 individuals were enrolled in this study; they were categorized into 4 groups: group 1 healthy individuals (NC) (n = 20), group 2 chronic hepatitis C virus (HCV) patients (n = 20), group 3 cirrhotic patients (LC) (n = 20), and HCC group (n = 20). Using ELISA technique serum levels of IL-6, IL-10, and alpha fetoprotein (AFP) were evaluated in all groups. Results. The mean serum levels of IL-6 were significantly higher in HCC than in LC, HCV, and NC groups (13.99 ± 1.80, 7.49 ± 0.43, 5.78 ± 0.74, and 2.57 ± 0.31), respectively (P < 0.05); also the serum levels of IL-10 were significantly higher in HCC compared with LC, HCV, and NC groups (13.69 ± 1.89, 7.37 ± 0.53, 5.18 ± 0.6, and 3.31 ± 0.42) (P < 0.05). We also found that the tumor size is correlated strongly with IL-6 and IL-10 levels (r = 0.925, P < 0.001; r = 0.821, P < 0.001), respectively. Conclusion. The combination of those markers may help to identify a group of HCC patients with low AFP. PMID:27335826

  11. Serum Levels of Interleukin-6 and Interleukin-10 as Biomarkers for Hepatocellular Carcinoma in Egyptian Patients

    PubMed Central

    Othman, Mohamed S.; Aref, Ahmed M.; Mohamed, Amal A.; Ibrahim, Wesam A.

    2013-01-01

    Interleukin-10 (IL-10) and interleukin-6 (IL-6) have been reported to be related to hepatocellular carcinoma (HCC) prognosis. This study aimed to investigate the clinical usefulness of serum levels of IL-6 and IL-10 as biomarkers for HCC among high-risk patients. Materials and Methods. 80 individuals were enrolled in this study; they were categorized into 4 groups: group 1 healthy individuals (NC) (n = 20), group 2 chronic hepatitis C virus (HCV) patients (n = 20), group 3 cirrhotic patients (LC) (n = 20), and HCC group (n = 20). Using ELISA technique serum levels of IL-6, IL-10, and alpha fetoprotein (AFP) were evaluated in all groups. Results. The mean serum levels of IL-6 were significantly higher in HCC than in LC, HCV, and NC groups (13.99 ± 1.80, 7.49 ± 0.43, 5.78 ± 0.74, and 2.57 ± 0.31), respectively (P < 0.05); also the serum levels of IL-10 were significantly higher in HCC compared with LC, HCV, and NC groups (13.69 ± 1.89, 7.37 ± 0.53, 5.18 ± 0.6, and 3.31 ± 0.42) (P < 0.05). We also found that the tumor size is correlated strongly with IL-6 and IL-10 levels (r = 0.925, P < 0.001; r = 0.821, P < 0.001), respectively. Conclusion. The combination of those markers may help to identify a group of HCC patients with low AFP. PMID:27335826

  12. A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases

    PubMed Central

    Davis, Ryan L.; Liang, Christina

    2016-01-01

    Objective: To directly compare the diagnostic utility of growth differentiation factor–15 (GDF-15) with our previous fibroblast growth factor–21 (FGF-21) findings in the same adult mitochondrial disease cohort. Methods: Serum GDF-15 levels were measured using a quantitative ELISA. Statistical analyses of GDF-15 data were compared with our published FGF-21 findings. Results: Median serum GDF-15 concentrations were elevated in patients with mitochondrial disease and differed between all experimental groups, mirroring group results for FGF-21. There was a difference between patients diagnosed by muscle biopsy and genetic diagnosis, suggesting that serum GDF-15 measurement may be more broadly specific for mitochondrial disease than for muscle manifesting mitochondrial disease, in contrast to FGF-21. GDF-15 showed a markedly higher diagnostic odds ratio when compared with FGF-21 (75.3 vs 45.7), was a better predictor of disease based on diagnostic sensitivity (77.8% vs 68.5%), and outperformed FGF-21 on receiver operating characteristic curve analysis (area under the curve 94.1% vs 91.1%). Combining both biomarkers did not improve the area under the curve remarkably over GDF-15 alone. GDF-15 was the best predictor of mitochondrial disease (p < 0.002) following multivariate logistic regression analysis. Conclusions: GDF-15 outperforms FGF-21 as an indicator of mitochondrial diseases. Our data suggest that GDF-15 is generally indicative of inherited mitochondrial disease regardless of clinical phenotype, whereas FGF-21 seems to be more indicative of mitochondrial disease when muscle manifestations are present. Classification of evidence: This study provides Class III evidence that serum GDF-15 accurately distinguishes patients with mitochondrial diseases from those without them. PMID:27164684

  13. Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer

    PubMed Central

    Willumsen, Nicholas; Bager, Cecilie L; Leeming, Diana J; Smith, Victoria; Christiansen, Claus; Karsdal, Morten A; Dornan, David; Bay-Jensen, Anne-Christine

    2014-01-01

    Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7–186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer. PMID:25044252

  14. Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice.

    PubMed Central

    Wilson, V S; McLachlan, J B; Falls, J G; LeBlanc, G A

    1999-01-01

    Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sex-specific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-1 mice. Gonadectomy followed by replacement of individual steroid hormones identified specific sex differences in biotransformation profiles that were due to the inductive or suppressive effects of testosterone. Notably, significant androgen-dependent differences in testosterone 6[alpha]- and 15[alpha]-hydroxylase activities were demonstrated, and the ratio of 6[alpha]- and 15[alpha]-hydroxylase activities proved to be an excellent indicator of the androgen status within the animal. The male or "masculinized" testosterone 6[alpha]/15[alpha]-hydroxylase ratio was significantly less than the female or "feminized" ratio. Male mice were exposed to both an antiandrogen, vinclozolin, and to a compound that modulates serum androgen levels, indole-3-carbinol, to test the utility of this ratio as a biomarker of androgen disruption. Treatment with the antiandrogen vinclozolin significantly increased the 6[alpha]/15[alpha]-hydroxylase ratio. Indole-3-carbinol treatment resulted in a dose-dependent, but highly variable, decrease in serum testosterone levels. The 6[alpha]/15[alpha]-hydroxylase ratio increased as serum testosterone levels decreased in these animals. However, the increase in the ratio was much less variable and more sensitive than serum testosterone levels. These investigations demonstrate that the 6[alpha]/15[alpha]-hydroxylase ratio is a powerful measure of androgen modulation and a sensitive indicator of exposure to androgen-disrupting chemicals in CD-1 mice. Images Figure 1 Figure 2

  15. Discovery of serum protein biomarkers in the mdx mouse model and cross-species comparison to Duchenne muscular dystrophy patients.

    PubMed

    Hathout, Yetrib; Marathi, Ramya L; Rayavarapu, Sree; Zhang, Aiping; Brown, Kristy J; Seol, Haeri; Gordish-Dressman, Heather; Cirak, Sebahattin; Bello, Luca; Nagaraju, Kanneboyina; Partridge, Terry; Hoffman, Eric P; Takeda, Shin'ichi; Mah, Jean K; Henricson, Erik; McDonald, Craig

    2014-12-15

    It is expected that serum protein biomarkers in Duchenne muscular dystrophy (DMD) will reflect disease pathogenesis, progression and aid future therapy developments. Here, we describe use of quantitative in vivo stable isotope labeling in mammals to accurately compare serum proteomes of wild-type and dystrophin-deficient mdx mice. Biomarkers identified in serum from two independent dystrophin-deficient mouse models (mdx-Δ52 and mdx-23) were concordant with those identified in sera samples of DMD patients. Of the 355 mouse sera proteins, 23 were significantly elevated and 4 significantly lower in mdx relative to wild-type mice (P-value < 0.001). Elevated proteins were mostly of muscle origin: including myofibrillar proteins (titin, myosin light chain 1/3, myomesin 3 and filamin-C), glycolytic enzymes (aldolase, phosphoglycerate mutase 2, beta enolase and glycogen phosphorylase), transport proteins (fatty acid-binding protein, myoglobin and somatic cytochrome-C) and others (creatine kinase M, malate dehydrogenase cytosolic, fibrinogen and parvalbumin). Decreased proteins, mostly of extracellular origin, included adiponectin, lumican, plasminogen and leukemia inhibitory factor receptor. Analysis of sera from 1 week to 7 months old mdx mice revealed age-dependent changes in the level of these biomarkers with most biomarkers acutely elevated at 3 weeks of age. Serum analysis of DMD patients, with ages ranging from 4 to 15 years old, confirmed elevation of 20 of the murine biomarkers in DMD, with similar age-related changes. This study provides a panel of biomarkers that reflect muscle activity and pathogenesis and should prove valuable tool to complement natural history studies and to monitor treatment efficacy in future clinical trials. PMID:25027324

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

    PubMed Central

    Basu, Arpita; Morris, Stacy; Nguyen, Angel; Betts, Nancy M.; Fu, Dongxu; Lyons, Timothy J.

    2016-01-01

    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. PMID:27429802

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

    PubMed

    Basu, Arpita; Morris, Stacy; Nguyen, Angel; Betts, Nancy M; Fu, Dongxu; Lyons, Timothy J

    2016-01-01

    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/m(2) (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. PMID:27429802

  18. Design and testing of a disposable microfluidic chemiluminescent immunoassay for disease biomarkers in human serum samples.

    PubMed

    Bhattacharyya, A; Klapperich, C M

    2007-04-01

    This paper presents the development of a plastic microfluidic immunosensor for rapid, reliable and on-the-spot detection of disease biomarkers in human sera. The microfluidic chips were fabricated in cyclic polyolefin by hot-embossing with a silicon master mold. The master itself was made using photolithographic techniques and Deep Reactive Ion Etching (DRIE). As a platform model, serum concentrations of C-reactive protein (CRP), a cardiac and inflammation marker, was measured on-chip using chemiluminescence based immunoassay. The assay results were read via an on-board instant photographic film, and with an imager capable of detecting chemiluminescent signals. The on-board detection module obviates the need for any dedicated bench-top analyzer for reading the immunoassay results, and therefore makes the device self-sufficient for point-of-care diagnostics when simple positive/negative results are sought. The microfluidic chemiluminescence results were compared with standard microplate ELISA analysis to assess the accuracy of the developed microfluidic immunoassay. Screening of CRP in human serum samples showed good correlation with ELISA analysis and the mean difference between the two methods using the Bland and Altman method was -0.079 +/- 0.858 mg/L for hsCRP. With approximate assay times of 25 min, the developed microfluidic immunoassay approach shows great potential for rapid plus sensitive detection of disease markers at the point-of-care.

  19. Cancer during pregnancy: what is the role of maternal serum and placental biomarkers? A review and commentary.

    PubMed

    Mizejewski, Gerald J

    2014-01-01

    Cancer during pregnancy, referred to as gestational cancer (GC), is infrequent but can occur in 1.0% of pregnant women. Hepatocellular carcinoma (HCC) is often lethal and is the fifth most common cancer worldwide, while breast adenocarcinoma (breast cancer) is the most common cancer seen during pregnancy. Liver and breast carcinomas are two examples of cancer types that present challenges to the obstetrician due to late and/or delayed diagnosis during pregnancy. Delays in diagnosis limit choices available to physicians regarding surgery, radiation, and chemotherapy. In view of such clinical situations, a role for maternal serum and placental biomarker (MSPB) screening results contributing to cancer diagnosis should be recognized; overlooking such data in GC could result from a lack of knowledge and understanding of MSPB biology, chemistry, and physiology. In this report, obstetricians and perinatologists seeking a diagnosis are urged to take advantage of available results from MSPB screening programs obtained from first- and second-trimester patient data. Using liver and breast cancer as examples, the present review and commentary seeks to demonstrate that MSPB levels, profiles, patterns, and cellular responses could provide foundational data in planning invasive or noninvasive methods and procedures (biopsy, imaging, scans, surgery) to attain a diagnosis as soon as possible in pregnancy. Finally, MSPB epidemiological and cancer risk studies could aid in providing baseline information for decisions regarding GC diagnosis from knowledge of their proposed roles in reducing lifetime risk of malignancies such as breast cancer.

  20. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus.

    PubMed

    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. PMID:27563164

  1. Inflammatory Biomarkers Profile as Microenvironmental Expression in Keratoconus

    PubMed Central

    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

  2. iTRAQ-Based Quantitative Proteomic Analysis Identified HSC71 as a Novel Serum Biomarker for Renal Cell Carcinoma

    PubMed Central

    Zhang, Yushi; Cai, Yi; Yu, Hongyan; Li, Hanzhong

    2015-01-01

    Renal cell carcinoma (RCC) is one of the most lethal urologic cancers and about 80% of RCC are of the clear-cell type (ccRCC). However, there are no serum biomarkers for the accurate diagnosis of RCC. In this study, we performed a quantitative proteomic analysis on serum samples from ccRCC patients and control group by using isobaric tag for relative and absolute quantitation (iTRAQ) labeling and LC-MS/MS analysis to access differentially expressed proteins. Overall, 16 proteins were significantly upregulated (ratio > 1.5) and 14 proteins were significantly downregulated (ratio < 0.67) in early-stage ccRCC compared to control group. HSC71 was selected and subsequently validated by Western blot in six independent sets of patients. ELISA subsequently confirmed HSC71 as a potential serum biomarker for distinguishing RCC from benign urologic disease with an operating characteristic curve (ROC) area under the curve (AUC) of 0.86 (95% confidence interval (CI), 0.76~0.96), achieving sensitivity of 87% (95% CI 69%~96%) at a specificity of 80% (95% CI 61~92%) with a threshold of 15 ng/mL. iTRAQ-based quantitative proteomic analysis led to identification of serum HSC71 as a novel serum biomarker of RCC, particularly useful in early diagnosis of ccRCC. PMID:26425554

  3. Dystromirs as serum biomarkers for monitoring the disease severity in Duchenne muscular Dystrophy.

    PubMed

    Zaharieva, Irina T; Calissano, Mattia; Scoto, Mariacristina; Preston, Mark; Cirak, Sebahattin; Feng, Lucy; Collins, James; Kole, Ryszard; Guglieri, Michela; Straub, Volker; Bushby, Kate; Ferlini, Alessandra; Morgan, Jennifer E; Muntoni, Francesco

    2013-01-01

    Duchenne muscular Dystrophy (DMD) is an inherited disease caused by mutations in the dystrophin gene that disrupt the open reading frame, while in frame mutations result in Becker muscular dystrophy (BMD). Ullrich congenital muscular dystrophy (UCMD) is due to mutations affecting collagen VI genes. Specific muscle miRNAs (dystromirs) are potential non-invasive biomarkers for monitoring the outcome of therapeutic interventions and disease progression. We quantified miR-1, miR-133a,b, miR-206 and miR-31 in serum from patients with DMD, BMD, UCMD and healthy controls. MiR-1, miR-133a,b and miR-206 were upregulated in DMD, but unchanged in UCMD compared to controls. Milder DMD patients had higher levels of dystromirs than more severely affected patients. Patients with low forced vital capacity (FVC) values, indicating respiratory muscle weakness, had low levels of serum miR-1 and miR-133b. There was no significant difference in the level of the dystromirs in BMD compared to controls. We also assessed the effect of dystrophin restoration on the expression of the five dystromirs in serum of DMD patients treated systemically for 12 weeks with antisense oligomer eteplirsen that induces skipping of exon 51 in the dystrophin gene. The dystromirs were also analysed in muscle biopsies of DMD patients included in a single dose intramuscular eteplirsen clinical trial. Our analysis detected a trend towards normalization of these miRNA between the pre- and post-treatment samples of the systemic trial, which however failed to reach statistical significance. This could possibly be due to the small number of patients and the short duration of these clinical trials. Although longer term studies are needed to clarify the relationship between dystrophin restoration following therapeutic intervention and the level of circulating miRNAs, our results indicate that miR-1 and miR-133 can be considered as exploratory biomarkers for monitoring the progression of muscle weakness and indirectly

  4. Influence of Long-Distance Bicycle Riding on Serum/Urinary Biomarkers of Prostate Cancer.

    PubMed

    Heger, Zbynek; Gumulec, Jaromir; Ondrak, Ales; Skoda, Jan; Zitka, Zdenek; Cernei, Natalia; Masarik, Michal; Zitka, Ondrej; Adam, Vojtech

    2016-01-01

    Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49-57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0-0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa-sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA. PMID:26999116

  5. Influence of Long-Distance Bicycle Riding on Serum/Urinary Biomarkers of Prostate Cancer

    PubMed Central

    Heger, Zbynek; Gumulec, Jaromir; Ondrak, Ales; Skoda, Jan; Zitka, Zdenek; Cernei, Natalia; Masarik, Michal; Zitka, Ondrej; Adam, Vojtech

    2016-01-01

    Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49–57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0–0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa—sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA. PMID:26999116

  6. Elevated serum microRNA-122/222 levels are potential diagnostic biomarkers in Egyptian patients with chronic hepatitis C but not hepatic cancer.

    PubMed

    Motawi, Tarek M K; Sadik, Nermin A H; Shaker, Olfat G; Ghaleb, Maggy H

    2016-07-01

    MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. Because of their size, specificity, and relative stability in plasma, miRNAs can be used as diagnostic and prognostic biomarkers to monitor liver injury, such as that caused by hepatitis C virus (HCV) and liver cancer. In this study, we investigated miRNA expression patterns from the serum of Egyptian patients with HCV and liver cancer compared with matched healthy controls. Using microarray-based expression profiling followed by real-time quantitative polymerase chain reaction validation, we compared the levels of circulating miRNA-122 and miRNA-222 in serum from patients with hepatitis C virus (n = 40) and liver cancer (n = 60) to matched healthy controls (n = 30). MiRNA SNORD68 was the housekeeping endogenous control. We found that the serum levels of miR-122 and miR-222 were significantly elevated in HCV patients, but not in liver cancer patients, compared with controls. Receiver operating characteristic analysis revealed that miR-122 and miR-222 have a high diagnostic potential in discriminating patients with HCV from controls. Serum miR-222 was significantly higher in HCV patients compared to liver cancer patients. Our results indicate that serum miR-122 and miR-222 are elevated in Egyptian patients with chronic HCV, and these miRNAs have a strong potential to serve as novel biomarkers for liver injury but not specifically for liver cancer.

  7. Serum-tryptase at diagnosis: a novel biomarker improving prognostication in Ph+ CML

    PubMed Central

    Sperr, Wolfgang R; Pfeiffer, Thomas; Hoermann, Gregor; Herndlhofer, Susanne; Sillaber, Christian; Mannhalter, Christine; Kundi, Michael; Valent, Peter

    2015-01-01

    Basophilia is an established prognostic variable in Ph-chromosome+ chronic myeloid leukemia (CML). However, in CML, basophils are often immature and thus escape microscopic quantification. We have previously shown that tryptase is produced and secreted by immature CML basophils. In the current study, serum samples of 79 CML patients (chronic phase=CP, n=69; accelerated/blast phase=AP/BP, n=10) treated with BCR/ABL inhibitors, were analyzed for their tryptase content. Serum-tryptase levels at diagnosis were found to correlate with basophil counts and were higher in AP/BP patients (median tryptase: 29.9 ng/mL) compared to patients with CP (11.7 ng/mL; p<0.05). In 20/69 patients with CP, progression occurred. The progression-rate was higher in patients with tryptase >15 ng/mL (31%) compared to those with normal tryptase levels (9%, p<0.05). To validate tryptase as new prognostic variable, we replaced basophils by tryptase levels in the EUTOS score. This modified EUTOS-T score was found to predict progression-free and event-free survival significantly better, with p values of 0.000064 and 0.00369, respectively, compared to the original EUTOS score (progression-free survival: p=0.019; event-free survival: p=0.156). In conclusion, our data show that the serum-tryptase level at diagnosis is a powerful prognostic biomarker in CML. Inclusion of tryptase in prognostic CML scores may improve their predictive value. PMID:25628944

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

    PubMed

    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. PMID:27000045

  9. Temporal changes in serum biomarkers and risk for progression of gastric precancerous lesions: A longitudinal study

    PubMed Central

    Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Long, Qi; Flanders, W. Dana; Bostick, Roberd M.; Yuan, Yuan

    2015-01-01

    Effectively managing precancerous lesions is crucial to reducing the gastric cancer (GC) burden. We evaluated associations of temporal changes in multiple serological markers (pepsinogen I [PGI], PGII, PGI/II ratio, gastrin-17 and anti-Helicobacter pylori IgG) with risk for progression of gastric precancerous lesions. From 1997 to 2011, repeated esophagogastroduodenoscopies with gastric mucosal biopsies and blood sample collections were conducted on 2,039 participants (5,070 person-visits) in the Zhuanghe Gastric Diseases Screening Program, Liaoning, China. Serum biomarkers were measured using ELISA, and gastric biopsies were evaluated using standardized histologic criteria. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations for correlated binary outcomes. The ORs for progression of gastric conditions comparing those whose serum PGI, PGII, and anti-H. pylori IgG levels increased ≥50% relative to those whose decreased ≥50% were, respectively 1.67 (CI, 1.22-2.28), 1.80 (CI, 1.40-2.33) and 1.93 (CI, 1.48-2.52). The OR for those whose PGI/II ratio decreased ≥50% relative to those whose increased 50% was 1.40 (CI, 1.08-1.81), and for those whose PGII and anti-H. pylori IgG levels both increased ≥50% relative to those whose levels both decreased 50% the OR was 3.18 (CI, 2.05-4.93). Changes in gastrin-17 were not statistically significantly associated with progression. These findings suggest that temporal changes in serum PGI, PGII, PGI/II ratio, and anti-H. pylori IgG levels (especially PGII and anti-H. pylori IgG combined) may be useful for assessing and managing risk for progression of gastric precancerous lesions. PMID:24895149

  10. Selective disturbances of serum mineral profiles by electroconvulsive therapy.

    PubMed

    Papavasiliou, P S; Miller, S T; Palat, G; Pleban, P; Mostek, W

    1985-07-01

    In nine patients with severe affective illness, the serum profiles of Mn, Zn, Cu, Mg, and Ca before and following successful bitemporal electroconvulsive therapy (ECT) were investigated. No elemental baseline abnormalities were detected before ECT. Both high and low level electric stimulation failed to produce changes in the serum concentrations of Mg as a function of time after ECT. Group mean concentrations of Zn, Cu, and Ca decreased after ECT, but values did not reach statistical significance. In contrast high level, but not low level, stimulation was accompanied by significant brief elevation of Mn (65%, p less than .02) followed by a progressive drop below basal levels (67%, p less than .001) 2 hours post-ECT. Similar patterns were observed during the middle and last ECT. Pre-ECT baseline Mn concentrations declined by about 44% (p less than .01) after the last ECT administration. The time course of these changes, in conjunction with evidence obtained from animal experimentation, suggests that high level ECT, irrespective of the onset of antidepressant effects, may alter extracellular Mn and consequently its normal intracellular composition as a result of the sudden increase in energy expenditure imposed by convulsive activity. Possible interactions between this element and other metabolic pathways are discussed. These changes may originate from elemental participation in restorative homeostatic metabolic processes during and after ECT.

  11. Comparison of the serum fibrin-fibrinogen degradation products with cytokeratin 19 fragment as biomarkers in patients with lung cancer.

    PubMed

    So, Hee Jin; Hong, Seok-Il; Lee, Jin Kyung; Chang, Yoon Hwan; Kang, Sun Jung; Hong, Young Jun

    2014-09-01

    Lung cancer is one of the main causes of cancer-related mortality. The identification of early diagnostic biomarkers improved outcomes for lung cancer patients. Serum fibrin-fibrinogen degradation products (FDP) levels are elevated in numerous malignancies due to hemostatic alterations. The serum FDP levels were compared to the levels of cytokeratin 19 fragment antigen (CYFRA 21-1), another well-established biomarker. The serum samples from 193 lung cancer patients, 84 healthy controls and 106 patients with benign respiratory diseases were obtained. The serum FDP level was measured using the DR-70 immunoassay and the CYFRA 21-1 level was measured by electrochemiluminescence using the Roche Analytics E170. Receiver operating characteristics curves were used to assess the predictive sensitivity and specificity. The mean serum FDP level in lung cancer patients (35.01±229.02 μg/ml) was significantly higher compared to the 190 non-cancerous subjects (0.60±0.75 μg/ml; P=0.039). The mean serum CYFRA 21-1 level in lung cancer patients (4.50±6.67 ng/ml) was also significantly higher compared to the non-cancerous subjects (1.40±0.83 ng/ml; P<0.05). FDP exhibited clinical sensitivity and specificity of 86 and 75%, respectively, at an optimal cut-off at 0.67 μg/ml. CYFRA 21-1 exhibited clinical sensitivity and specificity of 77 and 74%, respectively, at a cut-off of 1.65 ng/ml. The serum FDP area under the curve (0.87) was slightly higher compared to CYFRA 21-1 (0.83). Therefore, it is apparent that serum FDP is comparable to CYFRA 21-1 as a lung cancer biomarker and can be used for clinical practice. PMID:25054020

  12. DNA methylation profiles and biomarkers of oral squamous cell carcinoma

    PubMed Central

    Li, Yu-Fen; Hsiao, Yi-Hsiu; Lai, Yi-Hui; Chen, Yi-Chen; Chen, Ying-Ju; Chou, Jian-Liang; Chan, Michael W Y; Lin, Yu-Hsing; Tsou, Yung-An; Tsai, Ming-Hsui; Tai, Chien-Kuo

    2015-01-01

    Oral squamous cell carcinoma (OSCC) constitutes >90% of oral cancers and is the sixth most common malignancy among males worldwide and the fourth leading cause of death due to cancer among males in Taiwan. However, most patients do not receive a diagnosis of OSCC until the late stages, which have a lower survival rate. The use of molecular marker analysis to identify early-stage OSCC would permit optimal timing for treatments and consequently prolong survival. The aim of this study was to identify biomarkers of OSCC using the Illumina GoldenGate Methylation Cancer Panel, which comprised a total of 1,505 CpG sites covering 807 genes. Samples of buccal mucosa resected from 40 OSCC patients and normal tissue samples obtained from 15 patients (normal mucosa from OSCC patients or from patients undergoing surgery unrelated to OSCC) were analyzed. Fms-related tyrosine kinase 4 (FLT4) methylation exhibited a perfect specificity for detecting OSCC, with an area under the receiver operating characteristic curve of 0.91 for both all-stage and early-stage OSCC. Methylation of 7 genes (ASCL1, FGF3, FLT4, GAS7, KDR, TERT, and TFPI2) constitutes the top-20 panels for detecting OSCC. The top-20 panels for detecting early-stage OSCC contain 8 genes: ADCYAP1, EPHA7, FLT4, GSTM2, KDR, MT1A, NPY, and TFPI2. FLT4 RNA expression and methylation level were validated using RT-PCR and a pyrosequencing methylation assay. The median level of FLT4 expression was 2.14-fold for normal relative to OSCC tissue samples (P < 0.0001). Among the 8 pyrosequenced FLT4 CpG sites, methylation level was much higher in the OSCC samples. In conclusion, methylation statuses of selected genes, and especially FLT4, KDR, and TFPI2, might be of great potential as biomarkers for early detection of buccal OSCC. PMID:25612142

  13. Applying PET to Broaden the Diagnostic Utility of the Clinically Validated CA19.9 Serum Biomarker for Oncology

    PubMed Central

    Viola-Villegas, Nerissa Therese; Rice, Samuel L.; Carlin, Sean; Wu, Xiaohong; Evans, Michael J.; Sevak, Kuntal K.; Drobjnak, Marija; Ragupathi, Govind; Sawada, Ritsuko; Scholz, Wolfgang W.; Livingston, Philip O.; Lewis, Jason S.

    2014-01-01

    Despite their considerable advantages, many circulating biomarkers have well-documented limitations. One prominent shortcoming in oncology is a high frequency of false-positive indications for malignant disease in upfront diagnosis. Because one common cause of false positivism is biomarker production from benign disorders in unrelated host tissues, we hypothesized that probing the sites of biomarker secretion with an imaging tool could be a broadly useful strategy to deconvolute the meaning of foreboding but inconclusive circulating biomarker levels. Methods In preparation to address this hypothesis clinically, we developed 89Zr-5B1, a fully human, antibody-based radiotracer targeting tumor-associated CA19.9 in the preclinical setting. Results 89Zr-5B1 localized to multiple tumor models representing diseases with undetectable and supraphysiologic serum CA19.9 levels. Among these, 89Zr-5B1 detected orthotopic models of pancreatic ductal adenocarcinoma, an elusive cancer for which the serum assay is measured in humans but with limited specificity in part because of the frequency of CA19.9 secretion from benign hepatic pathologies. Conclusion In this report, a general strategy to supplement some of the shortcomings of otherwise highly useful circulating biomarkers with immunoPET is described. To expedite the clinical validation of this model, a human monoclonal antibody to CA19.9 (a highly visible but partially flawed serum biomarker for several cancers) was radiolabeled and evaluated, and the compelling preclinical evidence suggests that the radiotracer may enhance the fidelity of diagnosis and staging of pancreatic ductal adenocarcinoma, a notoriously occult cancer. PMID:24029655

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

    SciTech Connect

    Gilmour, Peter S.; O'Shea, Patrick J.; Fagura, Malbinder; Pilling, James E.; Sanganee, Hitesh; Wada, Hiroki; Courtney, Paul F.; Kavanagh, Stefan; Hall, Peter A.; Escott, K. Jane

    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

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

    ERIC Educational Resources Information Center

    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)

  16. Serum thymus and activation-regulated chemokine as disease activity and response biomarker in alopecia areata.

    PubMed

    Inui, Shigeki; Noguchi, Fumihito; Nakajima, Takeshi; Itami, Satoshi

    2013-11-01

    Serum thymus and activation-regulated chemokine/CCL17 (sTARC) is known as a good indicator for atopic dermatitis severity. Herein, we investigate whether sTARC correlates with severity and therapeutic response for alopecia areata (AA) in our 121 patients. The sTARC mean of AA totalis and universalis was significantly higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity-controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 ± 400.0 pg/mL) was significantly higher than that of the patchy type (344.0 ± 239.8 pg/mL), suggesting a potential role of TARC in active progression of diffuse AA. Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy. Then, we tested whether sTARC can predict prognosis after the pulse therapy and found that baseline sTARC in the poor responders (1025.5 ± 484.8 pg/mL) was significantly higher than that in the good responders (complete remission at 24 months after the pulse therapy, 347.8 ± 135.7 pg/mL), indicating sTARC as a response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally, to investigate TARC production in the affected hair follicles, we performed immunohistochemical double staining of TARC and CD68 using scalp skin specimens of diffuse AA with high titers of sTARC. The results showed their co-localization in the infiltrating cells around the AA hair follicles, suggesting that TARC is mainly produced from CD68(+) histiocytes. In conclusion, sTARC is a disease activity and response biomarker in AA, providing new insight beyond the T-helper 1/2 paradigm to solve the immunological pathogenesis of AA.

  17. Serum Osteopontin Predicts Degree of Hepatic Fibrosis and Serves as a Biomarker in Patients with Hepatitis C Virus Infection

    PubMed Central

    Matsue, Yasuhiro; Tsutsumi, Mikihiro; Hayashi, Nobuhiko; Saito, Takashi; Tsuchishima, Mutsumi; Toshikuni, Nobuyuki; Arisawa, Tomiyasu; George, Joseph

    2015-01-01

    Background & Aims Osteopontin (OPN) is a matricellular protein that upregulates during pathogenesis of hepatic fibrosis. The present study was aimed to evaluate whether serum OPN could be used as a biomarker to assess the degree of hepatic fibrosis in patients with hepatitis C virus (HCV) infection. Methods Needle biopsy was performed on HCV patients and scored as zero fibrosis (F0), mild fibrosis (F1), moderate fibrosis (F2), severe fibrosis (F3) and liver cirrhosis (F4) based on Masson’s trichrome and α-smooth muscle actin (α-SMA) staining. Serum OPN levels were measured using ELISA and correlated with the degree of fibrosis. Furthermore, the OPN values were correlated and evaluated with platelets count, serum hyaluronic acid (HA), and collagen type IV and subjected to receiver operating characteristic (ROC) curve analysis. Results Serum OPN levels were remarkably increased from F0 through F4 in a progressive manner and the differences were significant (P < 0.001) between each group. The data were highly correlated with the degree of hepatic fibrosis. The ROC curve analysis depicted that serum OPN is an independent risk factor and an excellent biomarker and a prognostic index in HCV patients. Conclusions The results of the present study indicate that serum OPN levels reflect the degree of hepatic fibrosis and could be used as a biomarker to assess the stage of fibrosis in HCV patients which would help to reduce the number of liver biopsies. Furthermore, serum OPN serves as a prognostic index towards the progression of hepatic fibrosis to cirrhosis and hepatocellular carcinoma. PMID:25760884

  18. Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma

    PubMed Central

    Kim, Seung Up; Kim, Hyon-Suk; Lee, Jae Myun; Lee, Hyun Gyu; Kim, Hyemi; Choi, Sung Hoon; Baek, Shinhwa; Kim, Beom Kyung; Park, Jun Yong; Kim, Do Young; Ahn, Sang Hoon; Lee, Jong Doo

    2015-01-01

    Purpose Dickkopf-1 (DKK-1) is a Wnt/β-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. Materials and Methods In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. Results RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p<0.001). The optimum DKK-1 cutoff level was 1.01 ng/mL (AUC=0.829; sensitivity 90.7%; specificity 62.0%). Although DKK-1 had a higher AUC than alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) (AUC=0.829 vs. 0.794 and 0.815, respectively), they were statistically similar (all p>0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). Conclusion DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP. PMID:26256972

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

    PubMed

    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.

  20. Polycyclic aromatic hydrocarbon biomarkers and serum markers of inflammation. A positive association that is more evident in men

    PubMed Central

    Alshaarawy, Omayma; Zhu, Motao; Ducatman, Alan; Conway, Baqiyyah; Andrew, Michael E.

    2015-01-01

    Background Polycyclic aromatic hydrocarbons (PAHs) are potent atmospheric pollutants, occurring from anthropogenic and natural sources. Several animal studies have reported a positive association of PAHs with inflammation. However, it is not clear if lower background exposure to PAHs is associated with inflammation in humans, independent of smoking, a major source of PAHs. Methods We examined participants from the National Health and Nutrition Examination Survey 2001– 2002, 2003–2004, and 2005–2006. Our exposures of interest were eight urinary monohydroxy polycyclic aromatic hydrocarbon biomarkers. Our outcomes were serum markers of inflammation; C-reactive protein (CRP) (≤10 mg/L) and total white blood cell (WBC) count (4000–12,000 cells/µL). Results Compared to participants with summed biomarkers of low-molecular weight (LMW) PAHs in the lowest quartile, the multivariable odds ratios (95% confidence interval) of high serum CRP (≥3 mg/L) and high total WBC count (defined as at or above the 95 percentile of total WBC distribution) among participants in the highest exposure quartile were 1.77 (1.13, 2.76) and 1.34 (1.12, 1.60) respectively. Urinary 1-hydroxypyrene, the biomarker of the higher molecular weight pyrene, was positively associated with total WBC count, and to lesser extent with serum CRP. In subsequent analyses, the positive association between LMW PAHs and serum CRP and total WBC count was found to be present within the stratified subgroups, independent of smoking and other potential confounders. The positive association was more evident among adult males when compared to females. Conclusions Urinary PAH biomarkers were found to be positively associated with serum CRP and total WBC count independent of smoking and other potential confounders. The association was more evident in men. PMID:23972896

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

    PubMed Central

    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

  2. Transcriptional profiling in facioscapulohumeral muscular dystrophy to identify candidate biomarkers

    PubMed Central

    Rahimov, Fedik; King, Oliver D.; Leung, Doris G.; Bibat, Genila M.; Emerson, Charles P.; Kunkel, Louis M.; Wagner, Kathryn R.

    2012-01-01

    Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder caused by contractions of repetitive elements within the macrosatellite D4Z4 on chromosome 4q35. The pathophysiology of FSHD is unknown and, as a result, there is currently no effective treatment available for this disease. To better understand the pathophysiology of FSHD and develop mRNA-based biomarkers of affected muscles, we compared global analysis of gene expression in two distinct muscles obtained from a large number of FSHD subjects and their unaffected first-degree relatives. Gene expression in two muscle types was analyzed using GeneChip Gene 1.0 ST arrays: biceps, which typically shows an early and severe disease involvement; and deltoid, which is relatively uninvolved. For both muscle types, the expression differences were mild: using relaxed cutoffs for differential expression (fold change ≥1.2; nominal P value <0.01), we identified 191 and 110 genes differentially expressed between affected and control samples of biceps and deltoid muscle tissues, respectively, with 29 genes in common. Controlling for a false-discovery rate of <0.25 reduced the number of differentially expressed genes in biceps to 188 and in deltoid to 7. Expression levels of 15 genes altered in this study were used as a “molecular signature” in a validation study of an additional 26 subjects and predicted them as FSHD or control with 90% accuracy based on biceps and 80% accuracy based on deltoids. PMID:22988124

  3. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    PubMed Central

    Saletta, Federica; Wadham, Carol; Ziegler, David S.; Marshall, Glenn M.; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D.; Byrne, Jennifer A.

    2014-01-01

    Background Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. Scope of review This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. Major conclusions There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. General significance The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations. PMID:26675306

  4. The Utility of Serum IgG4 Concentrations as a Biomarker

    PubMed Central

    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

  5. Identification of candidate diagnostic biomarkers for adolescent idiopathic scoliosis using UPLC/QTOF-MS analysis: a first report of lipid metabolism profiles

    PubMed Central

    Sun, Zhi-jian; Jia, Hong-mei; Qiu, Gui-xing; Zhou, Chao; Guo, Shigong; Zhang, Jian-guo; Shen, Jian-xiong; Zhao, Yu; Zou, Zhong-mei

    2016-01-01

    Adolescent idiopathic scoliosis (AIS) is a complex spine deformity, affecting approximately 1–3% adolescents. Earlier diagnosis could increase the likelihood of successful conservative treatment and hence reduce the need for surgical intervention. We conducted a serum metabonomic study to explore the potential biomarkers of AIS for early diagnosis. Serum metabolic profiles were firstly explored between 30 AIS patients and 31 healthy controls by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the candidate metabolites were validated in an independent cohort including 31 AIS patients and 44 controls. The results showed that metabolic profiles of AIS patients generally deviated from healthy controls in both the discovery set and replication set. Seven differential metabolites were identified as candidate diagnostic biomarkers, including PC(20:4), 2-hexenoylcarnitine, beta-D-glucopyranuronicacid, DG(38:9), MG(20:3), LysoPC(18:2) and LysoPC(16:0). These candidate metabolites indicated disrupted lipid metabolism in AIS, including glycerophospholipid, glycerolipid and fatty acid metabolism. Elevated expressions of adipose triglyceride lipase and hormone sensitive lipase in adipose tissue further corroborated our findings of increased lipid metabolism in AIS. Our findings suggest that differential metabolites discovered in AIS could be used as potential diagnostic biomarkers and that lipid metabolism plays a role in the pathogenesis of AIS. PMID:26928931

  6. Serum cystatin C and chitotriosidase in acute P-407 induced dyslipidemia: Can they serve as potential early biomarkers for atherosclerosis?

    PubMed

    Korolenko, T A; Pisareva, E E; Filyushina, E E; Johnston, T P; Machova, E

    2015-09-01

    In an attempt to better understand potential biomarkers for, and the role of macrophages in, the development of atherosclerosis, the toxicologic, and any therapeutic pharmacologic effects of carboxymethylated β-glucan, gadolinium chloride, and poloxamer 407 were studied in mice for their capacity to perturb serum lipids, cystatin C, and chitotriosidase-1. Gadolinium and carboxymethylated β-glucan dosed separately to control mice had no effect on serum lipids, whereas carboxymethylated β-glucan, but not gadolinium, exerted a significant (p<0.01) and unexpected hypolipidemic effect in poloxamer 407-induced hyperlipidemic mice. An acute hyperlipidemic state (∼4 days), induced with poloxamer 407 administration alone, resulted in a significant (p<0.01) time-dependent decrease and increase in serum cystatin C and chitotriosidase, respectively. Carboxymethylated β-glucan administration to hyperlipidemic mice significantly (p<0.05) increased the serum concentration of cystatin C, but significantly (p<0.01) decreased chitotriosidase activity, when each was compared to mice treated with poloxamer 407 only. Gadolinium administration caused a significant decrease in serum chitotriosidase activity in both controls (p<0.01) and poloxamer 407-induced hyperlipidemic (p<0.001) mice, but had no effect on the concentration of cystatin C in either controls or poloxamer 407-induced hyperlipidemic mice. Gadolinium administration resulted in both morphological and functional changes to liver macrophages, which included incorporation of excess lipids, especially when simultaneously administered with poloxamer 407. It is suggested that serum cystatin C and chitotriosidase may represent potential early biomarkers for eventual atherosclerosis in the poloxamer 407-induced mouse model of atherogenesis, and that two compounds known to either increase (carboxymethylated β-glucan) or decrease (gadolinium chloride) the number of macrophages in vivo were able to modulate serum

  7. Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

    PubMed Central

    Mawad, Habib; Laurin, Louis-Philippe; Naud, Jean-François; Leblond, François A.; Henley, Nathalie; Vallée, Michel; Pichette, Vincent; Leblanc, Martine

    2016-01-01

    OBJECTIVE The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. METHODS We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. RESULTS Baseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. CONCLUSIONS Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function. PMID:27398022

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

    PubMed Central

    Ortea, Ignacio; Roschitzki, Bernd; López-Rodríguez, Rosario; Tomero, Eva G.; Ovalles, Juan G.; López-Longo, Javier; de la Torre, Inmaculada; González-Alvaro, Isidoro; Gómez-Reino, Juan J.; González, Antonio

    2016-01-01

    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 indicate that they

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

    PubMed

    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. PMID:22618633

  10. AGR3 in Breast Cancer: Prognostic Impact and Suitable Serum-Based Biomarker for Early Cancer Detection

    PubMed Central

    Garczyk, Stefan; von Stillfried, Saskia; Antonopoulos, Wiebke; Hartmann, Arndt; Schrauder, Michael G.; Fasching, Peter A.; Anzeneder, Tobias; Tannapfel, Andrea; Ergönenc, Yavuz; Knüchel, Ruth

    2015-01-01

    Blood-based early detection of breast cancer has recently gained novel momentum, as liquid biopsy diagnostics is a fast emerging field. In this study, we aimed to identify secreted proteins which are up-regulated both in tumour tissue and serum samples of breast cancer patients compared to normal tissue and sera. Based on two independent tissue cohorts (n = 75 and n = 229) and one serum cohort (n = 80) of human breast cancer and healthy serum samples, we characterised AGR3 as a novel potential biomarker both for breast cancer prognosis and early breast cancer detection from blood. AGR3 expression in breast tumours is significantly associated with oestrogen receptor α (P<0.001) and lower tumour grade (P<0.01). Interestingly, AGR3 protein expression correlates with unfavourable outcome in low (G1) and intermediate (G2) grade breast tumours (multivariate hazard ratio: 2.186, 95% CI: 1.008-4.740, P<0.05) indicating an independent prognostic impact. In sera analysed by ELISA technique, AGR3 protein concentration was significantly (P<0.001) elevated in samples from breast cancer patients (n = 40, mainly low stage tumours) compared to healthy controls (n = 40). To develop a suitable biomarker panel for early breast cancer detection, we measured AGR2 protein in human serum samples in parallel. The combined AGR3/AGR2 biomarker panel achieved a sensitivity of 64.5% and a specificity of 89.5% as shown by receiver operating characteristic (ROC) curve statistics. Thus our data clearly show the potential usability of AGR3 and AGR2 as biomarkers for blood-based early detection of human breast cancer. PMID:25875093

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

    PubMed Central

    Fakanya, Wellington M.; Tothill, Ibtisam E.

    2014-01-01

    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. PMID:25587427

  12. Label-Free Kinetic Studies of Hemostasis-Related Biomarkers Including D-Dimer Using Autologous Serum Transfusion

    PubMed Central

    Winterhagen, Anna; Müller, Jens; Oldenburg, Johannes; Pötzsch, Bernd

    2015-01-01

    The objective of this study was to evaluate the elimination kinetics of hemostasis-related biomarkers including the prothrombin activation fragment F1+2, thrombin-antithrombin complex (TAT), plasmin-α2-antiplasmin complex (PAP), and D-dimer in humans. Autologous serum was used as a biomarker source and infused into 15 healthy volunteers. Serum was prepared from whole blood in the presence of recombinant tissue-type plasminogen activator (final concentration 20 μg/mL) to induce plasmin generation required for PAP and D-dimer formation. Serum transfusions (50 mL/30 min) were well tolerated by all subjects. Endogenous thrombin formation was not induced by serum infusions as measured using a highly sensitive oligonucleotide-based enzyme capture assay. Median peak levels (x-fold increase over baseline) of F1+2, TAT, PAP, and D-dimer of 3.7 nmol/L (28.9), 393 ng/mL (189.6), 3,829 ng/mL (7.0), and 13.4 mg/L (34.2) were achieved at the end of serum infusions. During a 48 h lasting follow-up period all biomarkers showed elimination kinetics of a two-compartment model. Median (interquartile range) terminal half-lives were 1.9 (1.3–3.6) h for F1+2, 0.7 (0.7–2.6) h for TAT, and 10.8 (8.8–11.4) h for PAP. With 15.8 (13.1–23.1) h the D-dimer half-life was about twice as long as previously estimated from radiolabeling studies in animals and small numbers of human subjects. The serum approach presented here allows label-free and simultaneous analysis of the elimination kinetics of various hemostasis-related biomarkers. Based on these data changes in biomarker levels could more precisely used to estimate the activity level of the hemostatic system. PMID:26658824

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

    SciTech Connect

    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.

  14. Prospective associations between serum biomarkers of lipid metabolism and overall, breast and prostate cancer risk.

    PubMed

    His, Mathilde; Zelek, Laurent; Deschasaux, Mélanie; Pouchieu, Camille; Kesse-Guyot, Emmanuelle; Hercberg, Serge; Galan, Pilar; Latino-Martel, Paule; Blacher, Jacques; Touvier, Mathilde

    2014-02-01

    Experimental studies provided evidence about mechanisms by which cholesterol, especially high density lipoprotein cholesterol (HDL-C), could influence carcinogenesis, notably through antioxidant and anti-inflammatory properties. However, prospective studies that investigated the associations between specific lipid metabolism biomarkers and cancer risk provided inconsistent results. The objective was to investigate the prospective associations between total cholesterol (T-C), HDL-C, low density lipoprotein cholesterol, apolipoproteins A1 (apoA1) and B, and triglycerides and overall, breast and prostate cancer risk. Analyses were performed on 7,557 subjects of the Supplémentation en Vitamines et Minéraux Antioxydants Study, a nationwide French cohort study. Biomarkers of lipid metabolism were measured at baseline and analyzed regarding the risk of first primary incident cancer (N = 514 cases diagnosed during follow-up, 1994-2007), using Cox proportional hazards models. T-C was inversely associated with overall (HR(1mmol/L increment) = 0.91, 95 % CI 0.82-1.00; P = 0.04) and breast (HR(1mmol/L increment) = 0.83, 95 % CI 0.69-0.99; P = 0.04) cancer risk. HDL-C was also inversely associated with overall (HR(1mmol/L increment) = 0.61, 95 % CI 0.46-0.82; P = 0.0008) and breast (HR(1mmol/L increment) = 0.48, 95 % CI 0.28-0.83; P = 0.009) cancer risk. Consistently, apoA1 was inversely associated with overall (HR(1g/L increment) = 0.56, 95 % CI 0.39-0.82; P = 0.003) and breast (HR(1g/L increment) = 0.36, 95 % CI 0.18-0.73; P = 0.004) cancer risk. This prospective study suggests that pre-diagnostic serum levels of T-C, HDL-C and ApoA1 are associated with decreased overall and breast cancer risk. The confirmation of a role of cholesterol components in cancer development, by further large prospective and experimental studies, may have important implications in terms of public health, since cholesterol is already crucial in cardiovascular prevention. PMID:24519551

  15. Serum miR-96 is a promising biomarker for hepatocellular carcinoma in patients with chronic hepatitis B virus infection

    PubMed Central

    Chen, Yueming; Dong, Xueyan; Yu, Daojun; Wang, Xianjun

    2015-01-01

    MicroRNAs (miRNAs) are involved in cancer biology, and some distinctive serum miRNAs could be useful for cancer diagnosis and prognosis. However, little is known about whether serum miR-96 is a satisfactory biomarker for hepatocellular carcinoma (HCC). Four hundreds and fourteen participants were enrolled in this study, and they were divided into four age- and gender-matched groups, including the HCC group (n = 104), liver cirrhosis (LC) group (n = 90), chronic hepatitis B (CHB) group (n = 100) and healthy control group (n = 120). Serum miR-96 was measured by real-time PCR, the levels of which were calculated by the 2-ΔCt method. Serum miR-96 levels in the HCC patients were remarkably higher than in the other groups (P < 0.01), and the serum miR-96 levels discriminated HCC patients from CHB patients with an area under the ROC curve (AUC) of 0.803 (77.9% sensitivity and 75.3% specificity). Furthermore, the AUC for combined miR-96 and α-fetoprotein (AFP) was 0.889 (83.6% sensitivity and 82.4% specificity). High serum miR-96 levels in HCC patients were associated with larger tumor size, higher prevalence of lymph node metastasis, higher TNM stage and worse overall survival (OS) (P < 0.05). Our findings suggest that serum miR-96 is a promising biomarker for HCC patients with chronic HBV infection. PMID:26770453

  16. Expression profile of long non-coding RNAs in pancreatic cancer and their clinical significance as biomarkers.

    PubMed

    Wang, Yingxue; Li, Zhihua; Zheng, Shangyou; Zhou, Yu; Zhao, Lei; Ye, Huilin; Zhao, Xiaohui; Gao, Wenchao; Fu, Zhiqiang; Zhou, Quanbo; Liu, Yimin; Chen, Rufu

    2015-11-01

    Long non-coding RNAs (lncRNAs) have shown great potential as powerful and non-invasive tumor markers. However, little is known about their value as biomarkers in pancreatic cancer (PC). We applied an Arraystar Human LncRNA Microarray which targeting 7419 lncRNAs to determine the lncRNA expression profile in PC and to screen the potential biomarkers. The most increased lncRNAs in PC tissues were HOTTIP-005, XLOC_006390, and RP11-567G11.1. Increased HOTTIP-005 and RP11-567G11.1 expression were poor prognostic factors for patients with PC (n = 144, p < 0.0001). The expression patterns of HOTTIP splice variants in PC were also detected. HOTTIP-005 and HOTTIP-001 were the first and second most increased HOTTIP splice variants, respectively. Plasma HDRF and RDRF (HOTTIP-005 and RP11-567G11.1 derived RNA fragments in plasma/serum) were present in stable form. Their levels were significantly increased in the patients with PC as compared to the healthy controls (n = 127 and 122 respectively, p < 0.0001) and the high levels were derived from PC. HDRF and RDRF levels are promising indicators for distinguishing patients with PC from those without PC. This study identified HOTTIP-005 and RP11-567G11.1 and their plasma fragments with the potential to be used as prognostic and diagnostic biomarkers of PC. Further large-scale prospective studies are needed to confirm our findings.

  17. Serum interferon-related microRNAs as biomarkers to predict the response to interferon therapy in chronic hepatitis C genotype 4.

    PubMed

    Motawi, Tarek Kamal; Shaker, Olfat Gamil; El-Maraghy, Shohda Assem; Senousy, Mahmoud Ahmed

    2015-01-01

    MicroRNAs are messengers during interferon-virus interplay and are involved in antiviral immunity, however, little is known about interferon-related microRNAs regarding their detection in serum and their potential use as non-invasive diagnostic and prognostic biomarkers in chronic hepatitis C (CHC). To elucidate some of the molecular aspects underlying failure of pegylated interferon-α/ribavirin therapy, we investigated pretreatment expression profiles of seven selected interferon-related microRNAs (miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296) by quantitative RT-PCR custom array technology in serum of Egyptian CHC genotype 4 patients and whether their pretreatment levels would predict patient response to the combination therapy. One hundred and six CHC patients and forty matched healthy controls were included. Patients were divided into sustained virological response (SVR) and non-responder (NR) groups. Serum miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296 were upregulated, whereas serum miR-146a was downregulated in CHC compared to controls. Significant correlations were found between expression levels of studied microRNAs and also with clinical data. Pretreatment levels of miR-34a, miR-130a, and miR-195 were significantly higher, whereas miR-192 and miR-296 levels were significantly lower in SVR than NR patients. miR-19a and miR-146a levels were not significantly different between the two groups. miR-34a was superior to differentiate CHC from controls, whereas miR-296 was superior to discriminate SVR from NR patients by receiver operating characteristic analysis. Multivariate logistic analysis revealed miR-34a and miR-195 as independent predictors for SVR and miR-192 as an independent variable for non-response. In conclusion, pretreatment expression profiles of five interferon-related microRNAs are associated with treatment outcome in CHC. Of these, miR-34a, miR-195, and miR-192 could predict treatment response. The profiling

  18. Serum interferon-related microRNAs as biomarkers to predict the response to interferon therapy in chronic hepatitis C genotype 4.

    PubMed

    Motawi, Tarek Kamal; Shaker, Olfat Gamil; El-Maraghy, Shohda Assem; Senousy, Mahmoud Ahmed

    2015-01-01

    MicroRNAs are messengers during interferon-virus interplay and are involved in antiviral immunity, however, little is known about interferon-related microRNAs regarding their detection in serum and their potential use as non-invasive diagnostic and prognostic biomarkers in chronic hepatitis C (CHC). To elucidate some of the molecular aspects underlying failure of pegylated interferon-α/ribavirin therapy, we investigated pretreatment expression profiles of seven selected interferon-related microRNAs (miR-146a, miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296) by quantitative RT-PCR custom array technology in serum of Egyptian CHC genotype 4 patients and whether their pretreatment levels would predict patient response to the combination therapy. One hundred and six CHC patients and forty matched healthy controls were included. Patients were divided into sustained virological response (SVR) and non-responder (NR) groups. Serum miR-34a, miR-130a, miR-19a, miR-192, miR-195, and miR-296 were upregulated, whereas serum miR-146a was downregulated in CHC compared to controls. Significant correlations were found between expression levels of studied microRNAs and also with clinical data. Pretreatment levels of miR-34a, miR-130a, and miR-195 were significantly higher, whereas miR-192 and miR-296 levels were significantly lower in SVR than NR patients. miR-19a and miR-146a levels were not significantly different between the two groups. miR-34a was superior to differentiate CHC from controls, whereas miR-296 was superior to discriminate SVR from NR patients by receiver operating characteristic analysis. Multivariate logistic analysis revealed miR-34a and miR-195 as independent predictors for SVR and miR-192 as an independent variable for non-response. In conclusion, pretreatment expression profiles of five interferon-related microRNAs are associated with treatment outcome in CHC. Of these, miR-34a, miR-195, and miR-192 could predict treatment response. The profiling

  19. The metabolomic profiling of serum in rats exposed to arsenic using UPLC/Q-TOF MS.

    PubMed

    Wang, Cheng; Feng, Rennan; Li, Yuanyuan; Zhang, Yunbo; Kang, Zhen; Zhang, Wei; Sun, Dian-Jun

    2014-09-17

    Chronic arsenicosis induced by excessive arsenic intake can cause damages to multi-organ systems, skin cancer and various internal cancers. However, the key metabolic changes and biomarkers which can reflect these changes remain unclear resulting in a lack of effective prevention and treatments. The aim of this study is to determine the impact of chronic arsenic exposure on the metabolism of organism, and find the metabolites changes by using metabolomic techniques. Thirty male Wistar rats were randomly divided into three groups. The arsenite was administered in water, and the doses were 0, 10, and 50mg/L, respectively. The exposure lasted for 6 months. The endogenous metabolite profile of serum was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Partial least squares discriminant analysis (PLS-DA) enabled clusters to be visualized. Nine serum principal metabolites contributing to the clusters were identified, which were CPA (18:2(9Z,12Z)/0:0), LysoPC (14:0), LysoPC (18:4 (6Z,9Z,12Z,15Z)), LysoPC (P-18:0), l-palmitoylcarnitine, LysoPC (20:2(11Z,14Z)) in positive ESI mode and deoxygcholylglycine, LysoPE (0:0/20:2(11Z,14Z)), 15(S)-hydroxyeicosatrienoic acid in negative ESI. These changes of metabolites in rats suggested the changed metabolism in rats exposed to arsenic. These findings may further aid diagnose and serve as targets for therapeutic intervention of arsenicosis.

  20. The metabolomic profiling of serum in rats exposed to arsenic using UPLC/Q-TOF MS.

    PubMed

    Wang, Cheng; Feng, Rennan; Li, Yuanyuan; Zhang, Yunbo; Kang, Zhen; Zhang, Wei; Sun, Dian-Jun

    2014-09-17

    Chronic arsenicosis induced by excessive arsenic intake can cause damages to multi-organ systems, skin cancer and various internal cancers. However, the key metabolic changes and biomarkers which can reflect these changes remain unclear resulting in a lack of effective prevention and treatments. The aim of this study is to determine the impact of chronic arsenic exposure on the metabolism of organism, and find the metabolites changes by using metabolomic techniques. Thirty male Wistar rats were randomly divided into three groups. The arsenite was administered in water, and the doses were 0, 10, and 50mg/L, respectively. The exposure lasted for 6 months. The endogenous metabolite profile of serum was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Partial least squares discriminant analysis (PLS-DA) enabled clusters to be visualized. Nine serum principal metabolites contributing to the clusters were identified, which were CPA (18:2(9Z,12Z)/0:0), LysoPC (14:0), LysoPC (18:4 (6Z,9Z,12Z,15Z)), LysoPC (P-18:0), l-palmitoylcarnitine, LysoPC (20:2(11Z,14Z)) in positive ESI mode and deoxygcholylglycine, LysoPE (0:0/20:2(11Z,14Z)), 15(S)-hydroxyeicosatrienoic acid in negative ESI. These changes of metabolites in rats suggested the changed metabolism in rats exposed to arsenic. These findings may further aid diagnose and serve as targets for therapeutic intervention of arsenicosis. PMID:24960056

  1. Comparison of serum creatinine and serum cystatin C as biomarkers to detect sepsis-induced acute kidney injury and to predict mortality in CD-1 mice.

    PubMed

    Leelahavanichkul, Asada; Souza, Ana Carolina P; Street, Jonathan M; Hsu, Victor; Tsuji, Takayuki; Doi, Kent; Li, Lingli; Hu, Xuzhen; Zhou, Hua; Kumar, Parag; Schnermann, Jürgen; Star, Robert A; Yuen, Peter S T

    2014-10-15

    Acute kidney injury (AKI) dramatically increases sepsis mortality, but AKI diagnosis is delayed when based on serum creatinine (SCr) changes, due in part, to decreased creatinine production. During experimental sepsis, we compared serum cystatin C (sCysC), SCr, and blood urea nitrogen (BUN) to inulin glomerular filtration rate (iGFR) before or 3-18 h after cecal ligation and puncture (CLP)-induced sepsis in CD-1 mice. sCysC had a faster increase and reached peak levels more rapidly than SCr in both sepsis and bilateral nephrectomy (BiNx) models. sCysC was a better surrogate of iGFR than SCr during sepsis. Combining sCysC with SCr values into a composite biomarker improved correlation with iGFR better than any biomarker alone or any other combination. We determined the renal contribution to sCysC handling with BiNx. sCysC and SCr were lower post-BiNx/CLP than post-BiNx alone, despite increased inflammatory and nonrenal organ damage biomarkers. Sepsis decreased CysC production in nephrectomized mice without changing body weight or CysC space. Sepsis decreased sCysC production and increased nonrenal clearance, similar to effects of sepsis on SCr. sCysC, SCr, and BUN were measured 6 h postsepsis to link AKI with mortality. Mice with above-median sCysC, BUN, or SCr values 6 h postsepsis died earlier than mice with below-median values, corresponding to a substantial AKI association with sepsis mortality in this model. sCysC performs similarly to SCr in classifying mice at risk for early mortality. We conclude that sCysC detects AKI early and better reflects iGFR in CLP-induced sepsis. This study shows that renal biomarkers need to be evaluated in specific contexts.

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

    SciTech Connect

    Hong, Wen-Xu; Liu, Wei; Zhang, Yanfang; Huang, Peiwu; Yang, Xifei; Ren, Xiaohu; Ye, Jinbo; Huang, Haiyan; Tang, Haiyan; Zhou, Guifeng; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun

    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.

  3. Screening and identification of five serum proteins as novel potential biomarkers for cured pulmonary tuberculosis

    PubMed Central

    Wang, Chong; Wei, Li-Liang; Shi, Li-Ying; Pan, Zhi-Fen; Yu, Xiao-Mei; Li, Tian-Yu; Liu, Chang-Ming; Ping, Ze-Peng; Jiang, Ting-Ting; Chen, Zhong-Liang; Mao, Lian-Gen; Li, Zhong-Jie; Li, Ji-Cheng

    2015-01-01

    Rapid and efficient methods for the determination of cured tuberculosis (TB) are lacking. A total of 85 differentially expressed serum proteins were identified by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) analysis (fold change >1.50 or <0.60, P < 0.05). We validated albumin (ALB), Rho GDP-dissociation inhibitor 2 (ARHGDIB), complement 3 (C3), ficolin-2 (FCN2), and apolipoprotein (a) (LPA) using the enzyme-linked immunosorbent assay (ELISA) method. Significantly increased ALB and LPA levels (P = 0.036 and P = 0.012, respectively) and significantly reduced ARHGDIB, C3, and FCN2 levels (P < 0.001, P = 0.035, and P = 0.018, respectively) were observed in cured TB patients compared with untreated TB patients. In addition, changes in ALB and FCN2 levels occurred after 2 months of treatment (P < 0.001 and P = 0.030, respectively). We established a cured TB model with 87.10% sensitivity, 79.49% specificity, and an area under the curve (AUC) of 0.876. The results indicated that ALB, ARHGDIB, C3, FCN2, and LPA levels might serve as potential biomarkers for cured TB. Our study provides experimental data for establishing objective indicators of cured TB and also proposes potential markers for evaluating the efficacy of anti-TB drugs. PMID:26499913

  4. Serum acetyl cholinesterase as a biomarker of arsenic induced neurotoxicity in sprague-dawley rats.

    PubMed

    Patlolla, Anita K; Tchounwou, Paul B

    2005-04-01

    Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 +/- 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW), one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 +/- 822, 5697 +/- 468, 5069 +/- 624, 4054 +/- 980, and 3158 +/- 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

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

    PubMed Central

    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.

    2015-01-01

    AIM: 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. SUBJECTS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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. PMID:27275191

  6. A metabolite profiling approach to identify biomarkers of flavonoid intake in humans.

    PubMed

    Loke, Wai Mun; Jenner, Andrew M; Proudfoot, Julie M; McKinley, Allan J; Hodgson, Jonathan M; Halliwell, Barry; Croft, Kevin D

    2009-12-01

    Flavonoids are phytochemicals that are widespread in the human diet. Despite limitations in their bioavailability, experimental and epidemiological data suggest health benefits of flavonoid consumption. Valid biomarkers of flavonoid intake may be useful for estimating exposure in a range of settings. However, to date, few useful flavonoid biomarkers have been identified. In this study, we used a metabolite profiling approach to examine the aromatic and phenolic profile of plasma and urine of healthy men after oral consumption of 200 mg of the pure flavonoids, quercetin, (-)-epicatechin, and epigallocatechin gallate, which represent major flavonoid constituents in the diet. Following enzymatic hydrolysis, 71 aromatic compounds were quantified in plasma and urine at 2 and 5 h, respectively, after flavonoid ingestion. Plasma concentrations of different aromatic compounds ranged widely, from 0.01 to 10 micromol/L, with variation among volunteers. None of the aromatic compounds was significantly elevated in plasma 2 h after consumption of either flavonoid compared with water placebo. This indicates that flavonoid-derived aromatic compounds are not responsible for the acute physiological effects reported within 2 h in previous human intervention studies involving flavonoids or flavonoid-rich food consumption. These effects are more likely due to absorption of the intact flavonoid. Our urine analysis suggested that urinary 4-ethylphenol, benzoic acid, and 4-ethylbenzoic acid may be potential biomarkers of quercetin intake and 1,3,5-trimethoxybenzene, 4-O-methylgallic acid, 3-O-methylgallic acid, and gallic acid may be potential markers of epigallocatechin gallate intake. Potential biomarkers of (-)-epicatechin were not identified. These urinary biomarkers may provide an accurate indication of flavonoid exposure. PMID:19812218

  7. A data-mining approach to biomarker identification from protein profiles using discrete stationary wavelet transform

    PubMed Central

    Montazery-Kordy, Hussain; Miran-Baygi, Mohammad Hossein; Moradi, Mohammad Hassan

    2008-01-01

    Objective: To develop a new bioinformatic tool based on a data-mining approach for extraction of the most informative proteins that could be used to find the potential biomarkers for the detection of cancer. Methods: Two independent datasets from serum samples of 253 ovarian cancer and 167 breast cancer patients were used. The samples were examined by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). The datasets were used to extract the informative proteins using a data-mining method in the discrete stationary wavelet transform domain. As a dimensionality reduction procedure, the hard thresholding method was applied to reduce the number of wavelet coefficients. Also, a distance measure was used to select the most discriminative coefficients. To find the potential biomarkers using the selected wavelet coefficients, we applied the inverse discrete stationary wavelet transform combined with a two-sided t-test. Results: From the ovarian cancer dataset, a set of five proteins were detected as potential biomarkers that could be used to identify the cancer patients from the healthy cases with accuracy, sensitivity, and specificity of 100%. Also, from the breast cancer dataset, a set of eight proteins were found as the potential biomarkers that could separate the healthy cases from the cancer patients with accuracy of 98.26%, sensitivity of 100%, and specificity of 95.6%. Conclusion: The results have shown that the new bioinformatic tool can be used in combination with the high-throughput proteomic data such as SELDI-TOF MS to find the potential biomarkers with high discriminative power. PMID:18988305

  8. Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas

    PubMed Central

    Riegler, Johannes; Ebert, Antje; Qin, Xulei; Shen, Qi; Wang, Mouer; Ameen, Mohamed; Kodo, Kazuki; Ong, Sang-Ging; Lee, Won Hee; Lee, Grace; Neofytou, Evgenios; Gold, Joseph D.; Connolly, Andrew J.; Wu, Joseph C.

    2016-01-01

    Summary The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm3. A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm3 and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking. PMID:26777057

  9. Proteomic profiling in MPTP monkey model for early Parkinson disease biomarker discovery

    PubMed Central

    Lin, Xiangmin; Shi, Min; Gunasingh Masilamoni, Jeyaraj; Dator, Romel; Movius, James; Aro, Patrick; Smith, Yoland; Zhang, Jing

    2015-01-01

    Identification of reliable and robust biomarkers is crucial to enable early diagnosis of Parkinson disease (PD) and monitoring disease progression. While imperfect, the slow, chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced non-human primate animal model system of parkinsonism is an abundant source of pre-motor or early stage PD biomarker discovery. Here, we present a study of a MPTP rhesus monkey model of PD that utilizes complementary quantitative iTRAQ-based proteomic, glycoproteomics and phosphoproteomics approaches. We compared the glycoprotein, non-glycoprotein, and phosphoprotein profiles in the putamen of asymptomatic and symptomatic MPTP-treated monkeys as well as saline injected controls. We identified 86 glycoproteins, 163 non-glycoproteins, and 71 phosphoproteins differentially expressed in the MPTP-treated groups. Functional analysis of the data sets inferred the biological processes and pathways that link to neurodegeneration in PD and related disorders. Several potential biomarkers identified in this study have already been translated for their usefulness in PD diagnosis in human subjects and further validation investigations are currently under way. In addition to providing potential early PD biomarkers, this comprehensive quantitative proteomic study may also shed insights regarding the mechanisms underlying early PD development. This article is part of a Special Issue entitled: Neuroproteomics: Applications in neuroscience and neurology. PMID:25617661

  10. Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure.

    PubMed

    Volta, Bibiana J; Bustos, Patricia L; Cardoni, Rita L; De Rissio, Ana M; Laucella, Susana A; Bua, Jacqueline

    2016-06-01

    Trypanosoma cruzi, the causing agent of Chagas disease, leads to an activation of the immune system in congenitally infected infants. In this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative PCR in the circulation of neonates born to T. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. We conducted a retrospective cohort study of 35 infants with congenital T. cruzi infection, of which 15 and 10 infants had been diagnosed by detection of parasites by microscopy in the first and sixth month after delivery, respectively, and the remaining 10 had been diagnosed by the presence of T. cruzi-specific Abs at 10-12 mo old. Uninfected infants born to either T. cruzi-infected or uninfected mothers were also evaluated as controls. The plasma levels of IL-17A, MCP-1, and monokine induced by IFN-γ were increased in infants congenitally infected with T. cruzi, even before they developed detectable parasitemia or seroconversion. Infants diagnosed between 6 and 12 mo old also showed increased levels of IL-6 and IL-17F at 1 mo of age. Conversely, infants who did not develop congenital T. cruzi infection had higher levels of IFN-γ than infected infants born to uninfected mothers. Monokine induced by IFN-γ, MCP-1, and IFN-γ production induced in T. cruzi-infected infants correlated with parasitemia, whereas the plasma levels of IL-17A, IL-17F, and IL-6 were less parasite load dependent. These findings support the existence of a distinct profile of cytokines and chemokines in the circulation of infants born to T. cruzi-infected mothers, which might predict congenital infection. PMID:27183607

  11. Serum Cytokines as Biomarkers of Early Trypanosoma cruzi infection by Congenital Exposure.

    PubMed

    Volta, Bibiana J; Bustos, Patricia L; Cardoni, Rita L; De Rissio, Ana M; Laucella, Susana A; Bua, Jacqueline

    2016-06-01

    Trypanosoma cruzi, the causing agent of Chagas disease, leads to an activation of the immune system in congenitally infected infants. In this study, we measured a set of cytokines/chemokines and the levels of parasitemia by quantitative PCR in the circulation of neonates born to T. cruzi-infected mothers to evaluate the predictive value of these mediators as biomarkers of congenital transmission. We conducted a retrospective cohort study of 35 infants with congenital T. cruzi infection, of which 15 and 10 infants had been diagnosed by detection of parasites by microscopy in the first and sixth month after delivery, respectively, and the remaining 10 had been diagnosed by the presence of T. cruzi-specific Abs at 10-12 mo old. Uninfected infants born to either T. cruzi-infected or uninfected mothers were also evaluated as controls. The plasma levels of IL-17A, MCP-1, and monokine induced by IFN-γ were increased in infants congenitally infected with T. cruzi, even before they developed detectable parasitemia or seroconversion. Infants diagnosed between 6 and 12 mo old also showed increased levels of IL-6 and IL-17F at 1 mo of age. Conversely, infants who did not develop congenital T. cruzi infection had higher levels of IFN-γ than infected infants born to uninfected mothers. Monokine induced by IFN-γ, MCP-1, and IFN-γ production induced in T. cruzi-infected infants correlated with parasitemia, whereas the plasma levels of IL-17A, IL-17F, and IL-6 were less parasite load dependent. These findings support the existence of a distinct profile of cytokines and chemokines in the circulation of infants born to T. cruzi-infected mothers, which might predict congenital infection.

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

    PubMed Central

    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

  13. Exploring metabolic syndrome serum free fatty acid profiles based on GC-SIM-MS combined with random forests and canonical correlation analysis.

    PubMed

    Dai, Ling; Gonçalves, Carlos M Vicente; Lin, Zhang; Huang, Jianhua; Lu, Hongmei; Yi, Lunzhao; Liang, Yizeng; Wang, Dongsheng; An, Dong

    2015-04-01

    Metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with an increased risk of developing cardiovascular diseases or type II diabetes. Till now, the etiology of MetS is complex and still unknown. Metabolic profiling is a powerful tool for exploring metabolic perturbations and potential biomarkers, thus may shed light on the pathophysiological mechanism of diseases. In this study, fatty acid profiling was employed to exploit the metabolic disturbances and discover potential biomarkers of MetS. Fatty acid profiles of serum samples from metabolic syndrome patients and healthy controls were first analyzed by gas chromatography-selected ion monitoring-mass spectrometry (GC-SIM-MS), a robust method for quantitation of fatty acids. Then, the supervised multivariate statistical method of random forests (RF) was used to establish a classification and prediction model for MetS, which could assist the diagnosis of MetS. Furthermore, canonical correlation analysis (CCA) was employed to investigate the relationships between free fatty acids (FFAs) and clinical parameters. As a result, several FFAs, including C16:1n-9c, C20:1n-9c and C22:4n-6c, were identified as potential biomarkers of MetS. The results also indicated that high density lipoprotein-cholesterol (HDL-C), triglycerides (TG) and fasting blood glucose (FBG) were the most important parameters which were closely correlated with FFAs disturbances of MetS, thus they should be paid more attention in clinical practice for monitoring FFAs disturbances of MetS than waist circumference (WC) and systolic blood pressure/diastolic blood pressure (SBP/DBP). The results have demonstrated that metabolic profiling by GC-SIM-MS combined with RF and CCA may be a useful tool for discovering the perturbations of serum FFAs and possible biomarkers for MetS.

  14. The Identification of Circulating MiRNA in Bovine Serum and Their Potential as Novel Biomarkers of Early Mycobacterium avium subsp paratuberculosis Infection

    PubMed Central

    Britton, Louise; MacHugh, David E.; Markey, Bryan; Gordon, Stephen V.

    2015-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne’s disease (JD), a chronic enteritis in ruminants that causes substantial economic loses to agriculture worldwide. Current diagnostic assays are hampered by low sensitivity and specificity that seriously complicate disease control; a new generation of diagnostic and prognostic assays are therefore urgently needed. Circulating microRNAs (miRNAs) have been shown to have significant potential as novel biomarkers for a range of human diseases, but their potential application in the veterinary sphere has been less well characterised. The aim of this study was therefore to apply RNA-sequencing approaches to serum from an experimental JD infection model as a route to identify novel diagnostic and prognostic miRNA biomarkers. Sera from experimental MAP-challenged calves (n = 6) and age-matched controls (n = 6) were used. We identified a subset of known miRNAs from bovine serum across all samples, with approximately 90 being at potentially functional abundance levels. The majority of known bovine miRNAs displayed multiple isomiRs that differed from the canonical sequences. Thirty novel miRNAs were identified after filtering and were found within sera from all animals tested. No significant differential miRNA expression was detected when comparing sera from MAP-challenged animals to their age-matched controls at six-month’s post-infection. However, comparing sera from pre-infection bleeds to six-month’s post-infection across all 12 animals did identify increased miR-205 (2-fold) and decreased miR-432 (2-fold) within both challenged and control groups, which suggests changes in circulating miRNA profiles due to ageing or development (P<0.00001). In conclusion our study has identified a range of novel miRNA in bovine serum, and shown the utility of small RNA sequencing approaches to explore the potential of miRNA as novel biomarkers for infectious disease in cattle. PMID:26218736

  15. Plasma biomarker profiling in the detection of growth promoter use in calves.

    PubMed

    Mooney, M H; Situ, C; Cacciatore, G; Hutchinson, T; Elliott, C; Bergwerff, A A

    2008-05-01

    The detection of illicit growth promoter use during meat production within the European Union is reliant on residue testing which is a limiting factor on the number of animals which can be tested and consequently compromises the efficacy of testing procedures. The present study examined a novel detection strategy based on the profiling of plasma component concentrations in response to growth promoter administrations. Calves subjected to nortestosterone decanoate, 17beta-oestradiol benzoate and dexamethasone were found to have altered urea, aminoterminal propeptide of type III procollagen and sex hormone binding globulin profiles in response to treatments. These findings demonstrate the potential of using the identification of perturbed profiles within a panel of biomarkers which cover a spectrum of biological activity to reveal growth promoter abuse.

  16. Searching biomarker candidates in serum using multidimensional native chromatography. II Method evaluation with Alport syndrome and severe inflammation.

    PubMed

    Baum, Adrienne; Pohl, Michael; Kreusch, Stefan; Cumme, Gerhard A; Ditze, Günter; Misselwitz, Joachim; Kiehntopf, Michael; Udby, Lene; Meier-Hellmann, Andreas; Rhode, Heidrun

    2008-12-01

    Biomarker search using multidimensional native liquid fractionation of serum in microplates was evaluated. From different donors, homologous sample fractions with UV absorbance depending on state of illness were selected, and their constituents were identified and quantitated by MS. Analysis of sera of patients with Alport syndrome and severe inflammation proved the reliability of the method by confirming characteristic alterations. Moreover, 23 new marker candidates were detected for Alport syndrome, some of them being involved in matrix degradation and repair, and 33 new candidates for severe inflammation, among them alpha1B-glycoprotein cysteine-rich secretory protein and an apparently low molecular-weight albumin variant. PMID:18952508

  17. Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury.

    PubMed

    Robinson, Shenandoah; Winer, Jesse L; Berkner, Justin; Chan, Lindsay A S; Denson, Jesse L; Maxwell, Jessie R; Yang, Yirong; Sillerud, Laurel O; Tasker, Robert C; Meehan, William P; Mannix, Rebekah; Jantzie, Lauren L

    2016-06-01

    OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0

  18. Imaging and serum biomarkers reflecting the functional efficacy of extended erythropoietin treatment in rats following infantile traumatic brain injury.

    PubMed

    Robinson, Shenandoah; Winer, Jesse L; Berkner, Justin; Chan, Lindsay A S; Denson, Jesse L; Maxwell, Jessie R; Yang, Yirong; Sillerud, Laurel O; Tasker, Robert C; Meehan, William P; Mannix, Rebekah; Jantzie, Lauren L

    2016-06-01

    OBJECTIVE Traumatic brain injury (TBI) is a leading cause of death and severe morbidity for otherwise healthy full-term infants around the world. Currently, the primary treatment for infant TBI is supportive, as no targeted therapies exist to actively promote recovery. The developing infant brain, in particular, has a unique response to injury and the potential for repair, both of which vary with maturation. Targeted interventions and objective measures of therapeutic efficacy are needed in this special population. The authors hypothesized that MRI and serum biomarkers can be used to quantify outcomes following infantile TBI in a preclinical rat model and that the potential efficacy of the neuro-reparative agent erythropoietin (EPO) in promoting recovery can be tested using these biomarkers as surrogates for functional outcomes. METHODS With institutional approval, a controlled cortical impact (CCI) was delivered to postnatal Day (P)12 rats of both sexes (76 rats). On postinjury Day (PID)1, the 49 CCI rats designated for chronic studies were randomized to EPO (3000 U/kg/dose, CCI-EPO, 24 rats) or vehicle (CCI-veh, 25 rats) administered intraperitoneally on PID1-4, 6, and 8. Acute injury (PID3) was evaluated with an immunoassay of injured cortex and serum, and chronic injury (PID13-28) was evaluated with digitized gait analyses, MRI, and serum immunoassay. The CCI-veh and CCI-EPO rats were compared with shams (49 rats) primarily using 2-way ANOVA with Bonferroni post hoc correction. RESULTS Following CCI, there was 4.8% mortality and 55% of injured rats exhibited convulsions. Of the injured rats designated for chronic analyses, 8.1% developed leptomeningeal cyst-like lesions verified with MRI and were excluded from further study. On PID3, Western blot showed that EPO receptor expression was increased in the injured cortex (p = 0.008). These Western blots also showed elevated ipsilateral cortex calpain degradation products for αII-spectrin (αII-SDPs; p < 0

  19. Systemic complement profiling in multiple sclerosis as a biomarker of disease state

    PubMed Central

    Ingram, G; Hakobyan, S; Hirst, CL; Harris, CL; Loveless, S; Mitchell, JP; Pickersgill, TP; Robertson, NP

    2012-01-01

    Background: There is increasing evidence of significant and dynamic systemic activation and upregulation of complement in multiple sclerosis (MS), which may contribute to disease pathogenesis. Objective: We aimed to investigate the pathological role of complement in MS and the potential role for complement profiling as a biomarker of MS disease state. Methods: Key components of the classical, alternative and terminal pathways of complement were measured in plasma and cerebrospinal fluid (CSF) of patients with MS in different clinical phases of disease and in matched controls. Results: Increased plasma levels of C3 (p<0.003), C4 (p<0.001), C4a (p<0.001), C1 inhibitor (p<0.001), and factor H (p<0.001), and reduced levels of C9 (p<0.001) were observed in MS patients compared with controls. Combined profiling of these analytes produced a statistical model with a predictive value of 97% for MS and 73% for clinical relapse when combined with selected demographic data. CSF-plasma correlations suggested that source of synthesis of these components was both systemic and central. Conclusion: These data provide further evidence of alterations in both local and systemic expression and activation of complement in MS and suggest that complement profiling may be informative as a biomarker of MS disease, although further work is needed to determine its use in distinguishing MS from its differential. PMID:22354735

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

    PubMed Central

    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 < 0.001). In the 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. Conclusions: 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. 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

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

    PubMed

    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.

  2. Association between coffee consumption and serum lipid profile

    PubMed Central

    KARABUDAK, EFSUN; TÜRKÖZÜ, DUYGU; KÖKSAL, EDA

    2015-01-01

    The aim of the present study was to investigate the association between coffee consumption and serum lipid levels in a study population of 122 Turkish subjects (mean age, 41.4±12.69 years), including 48 males and 74 females. A questionnaire was compiled to determine baseline characteristics, and food and coffee consumption. Subjects were divided into three groups, which included non-drinkers, Turkish coffee and instant coffee drinkers, and anthropometric measurements were acquired, including weight, height and body mass index. Serum lipid levels were analyzed, including the total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels. Of the population studied, 76.2% had consumed at least one cup of coffee per week over the previous year. Daily consumption values were 62.3±40.60 ml (0.7±0.50 cup) for Turkish coffee and 116.3±121.96 ml (0.7±0.81 cup) for instant coffee. No statistically significant differences were observed in the serum levels of TC, TG, LDL-C, HDL-C or VLDL-C among the three groups. In addition, no statistically significant differences were observed in the serum lipid levels when comparing individuals who consumed coffee with sugar/cream or who smoked and those who did not (P>0.05). Therefore, the present observations indicated no significant association between the consumption of Turkish or instant coffee and serum lipid levels. PMID:26136902

  3. A cross sectional study of two independent cohorts identifies serum biomarkers for facioscapulohumeral muscular dystrophy (FSHD).

    PubMed

    Petek, Lisa M; Rickard, Amanda M; Budech, Christopher; Poliachik, Sandra L; Shaw, Dennis; Ferguson, Mark R; Tawil, Rabi; Friedman, Seth D; Miller, Daniel G

    2016-07-01

    Measuring the severity and progression of facioscapulohumeral muscular dystrophy (FSHD) is particularly challenging because muscle weakness progresses over long periods of time and can be sporadic. Biomarkers are essential for measuring disease burden and testing treatment strategies. We utilized the sensitive, specific, high-throughput SomaLogic proteomics platform of 1129 proteins to identify proteins with levels that correlate with FSHD severity in a cross-sectional study of two independent cohorts. We discovered biomarkers that correlate with clinical severity and disease burden measured by magnetic resonance imaging. Sixty-eight proteins in the Rochester cohort (n = 48) and 51 proteins in the Seattle cohort (n = 30) had significantly different levels in FSHD-affected individuals when compared with controls (p-value ≤ .005). A subset of these varied by at least 1.5 fold and four biomarkers were significantly elevated in both cohorts. Levels of creatine kinase MM and MB isoforms, carbonic anhydrase III, and troponin I type 2 reliably predicted the disease state and correlated with disease severity. Other novel biomarkers were also discovered that may reveal mechanisms of disease pathology. Assessing the levels of these biomarkers during clinical trials may add significance to other measures of quantifying disease progression or regression. PMID:27185459

  4. Establishment of Magnetic Microparticles-Assisted Time-Resolved Fluoroimmunoassay for Determinating Biomarker Models in Human Serum

    PubMed Central

    Ren, Zhi-Qi; Liu, Tian-Cai; Zhuang, Si-Hui; Lin, Guan-Feng; Hou, Jing-Yuan; Wu, Ying-Song

    2015-01-01

    In order to early screen and detect suspected biomarkers from pathogens and the human body itself, tracers or reaction strategies that can act as signal enhancers have been proposed forth at purpose. In this paper, we discussed the applicability of magnetic microparticles-assisted time-resolved fluoroimmunoassay (MMPs-TRFIA) for sensitive determination of potential analytes. Hepatitis B e antigen, antibody to hepatitis B surface antigen and free triiodothyronine were used as biomarker models to explore the reliability of the method. By coupling with bioprobes, MMPs were used as immunoassay carriers to capture target molecules. Under optimal condition, assay performance, including accuracy, precision and specificity, was outstanding and demonstrated satisfactory. To further evaluate the performance of the MMPs-TRFIA in patients, a total of 728 serum samples from hospital were analyzed for three biomarkers in parallel with the proposed method and chemiluminescence immunoassay kit commercially available. Fairly good agreements are obtained between the two methods via data analysis. Not only that but the reliability of MMPs-TRFIA has also been illustrated by three different reaction models. It is confirmed that the novel method modified with MMPs has been established and showed great potential applications in both biological detection and clinical diagnosis, including big molecule protein and low molecular weight haptens. PMID:26103625

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

    PubMed Central

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

    2016-01-01

    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. PMID:26909861

  6. Serum enolase: a non-destructive biomarker of white skeletal myopathy during pancreas disease (PD) in Atlantic salmon Salmo salar L.

    PubMed

    Braceland, M; McLoughlin, M F; Tinsley, J; Wallace, C; Cockerill, D; McLaughlin, M; Eckersall, P D

    2015-09-01

    Diseases which cause skeletal muscle myopathy are some of the most economically damaging diseases in Atlantic salmon, Salmo salar L., aquaculture. Despite this, there are limited means of assessing fish health non-destructively. Previous investigation of the serum proteome of Atlantic salmon, Salmo salar L., during pancreas disease (PD) has identified proteins in serum that have potential as biomarkers of the disease. Amongst these proteins, the enzyme enolase was selected as the most viable for use as a biomarker of muscle myopathy associated with PD. Western blot and immunoassay (ELISA) validated enolase as a biomarker for PD, whilst immunohistochemistry identified white muscle as the source of enolase. Enolase was shown to be a specific marker for white muscle myopathy in salmon, rising in serum concentration significantly correlating with pathological damage to the tissue.

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

    PubMed

    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.

  8. Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction

    PubMed Central

    Koh, Yoon-Seok; Seo, Suk Min; Park, Won Sang; Lee, Jung Young; Chang, Kiyuk; Seung, Ki Bae; Kim, Pum-Joon; Nam, Suk Woo

    2015-01-01

    Blood transcriptome reflects the status of diseases, and characteristic molecular signature provides a novel window on gene expression preceding acute coronary events. We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI). We obtained peripheral blood from the patients with ACS who visited emergency department within 4 hours after the onset of chest pain: STEMI (n = 10), Non-ST-segment-elevation MI (NSTEMI, n = 10) and unstable angina (UA, n = 11). Blood transcriptome scans revealed that a characteristic gene expression change exists in STEMI, resulting in 531 outlier genes as STEMI molecular signature (Welch's t test, P < 0.05). Another analysis with a set of blood samples of patients with STEMI (n = 7) before and 7 days after the primary percutaneous coronary intervention (n = 7) and normal control (n = 10) evidenced that STEMI molecular signature directly reflects the onset of STEMI pathogenesis. From the two sets of transcriptome-based STEMI signatures, we identified 10 genes encoding transmembrane or secretory proteins that are highly expressed in STEMI. We validated blood protein expression levels of these 10 putative biomarkers in 40 STEMI and 32 healthy subjects by ELISA. Data suggested that PGLYRP1, IRAK3 and VNN3 are more specific and sensitive diagnostic biomarkers for STEMI than traditional CK-MB or troponin. Blood transcriptome scans of ACS evidenced early stage molecular markers for STEMI. Here, we report novel biomarkers to diagnose STEMI at emergency department in hospitals by a simple ELISA method. PMID:26025919

  9. High-resolution taxonomic profiling of the subgingival microbiome for biomarker discovery and periodontitis diagnosis.

    PubMed

    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; Wagner-Döbler, Irene

    2015-02-01

    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.

  10. Supplementation of zilpaterol hydrochloride does not significantly alter the serum metabolic profile and metabolic enzyme profile of finishing heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Supplementation of zilpaterol hydrochloride (ZH; Zilmax®) to cattle has been implicated as having a negative impact on the well-being of cattle. However, there is no data to support or refute these claims. This study was designed to determine if differences exist in the serum metabolic profile and m...

  11. Detection of Soluble ED-A(+) Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling.

    PubMed

    Ziffels, Barbara; Ospel, Johanna; Grün, Katja; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R; Jung, Christian; Berndt, Alexander; Franz, Marcus

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A(+) Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A(+) Fn in serum of heart failure patients. Methods. ED-A(+) Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A(+) Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A(+) Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: -0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A(+) Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A(+) Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A(+) Fn. PMID:27635109

  12. Serum Proteomic Changes after Randomized Prolonged Erythropoietin Treatment and/or Endurance Training: Detection of Novel Biomarkers

    PubMed Central

    Christensen, Britt; Ludvigsen, Maja; Nellemann, Birgitte; Kopchick, John J.; Honoré, Bent; Jørgensen, Jens Otto L.

    2015-01-01

    Introduction 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. Trial Design 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. Methods 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. Results 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. Conclusion An isoform of haptoglobin/haptoglobin related protein could be a new anti-doping marker and merits further research. Trial Registration ClinicalTrials.gov NCT01320449 PMID:25679398

  13. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling

    PubMed Central

    Ospel, Johanna; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R.; Jung, Christian; Berndt, Alexander

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: −0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn. PMID:27635109

  14. Detection of Soluble ED-A+ Fibronectin and Evaluation as Novel Serum Biomarker for Cardiac Tissue Remodeling

    PubMed Central

    Ospel, Johanna; Neri, Dario; Pfeil, Alexander; Fritzenwanger, Michael; Figulla, Hans R.; Jung, Christian; Berndt, Alexander

    2016-01-01

    Background and Aims. Fibronectin containing the extra domain A (ED-A+ Fn) was proven to serve as a valuable biomarker for cardiac remodeling. The study was aimed at establishing an ELISA to determine ED-A+ Fn in serum of heart failure patients. Methods. ED-A+ Fn was quantified in serum samples from 114 heart failure patients due to ischemic (ICM, n = 44) and dilated (DCM, n = 39) cardiomyopathy as well as hypertensive heart disease (HHD, n = 31) compared to healthy controls (n = 12). Results. In comparison to healthy volunteers, heart failure patients showed significantly increased levels of ED-A+ Fn (p < 0.001). In particular in ICM patients there were significant associations between ED-A+ Fn serum levels and clinical parameters, for example, increased levels with rising NYHA class (p = 0.013), a negative correlation with left ventricular ejection fraction (p = 0.026, r: −0.353), a positive correlation with left atrial diameter (p = 0.008, r: 0.431), and a strong positive correlation with systolic pulmonary artery pressure (p = 0.002, r: 0.485). In multivariate analysis, ED-A+ Fn was identified as an independent predictor of an ischemic heart failure etiology. Conclusions. The current study could clearly show that ED-A+ Fn is a promising biomarker in cardiovascular diseases, especially in heart failure patients due to an ICM. We presented a valid ELISA method, which could be applied for further studies investigating the value of ED-A+ Fn.

  15. Early and Delayed Effects of Naturally Occurring Asbestos on Serum Biomarkers of Inflammation and Metabolism

    EPA Science Inventory

    Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; a-2 macroglobulin, A2M; and a-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives...

  16. Metabolomics-Based Discovery of Small Molecule Biomarkers in Serum Associated with Dengue Virus Infections and Disease Outcomes

    PubMed Central

    Voge, Natalia V.; Perera, Rushika; Mahapatra, Sebabrata; Gresh, Lionel; Balmaseda, Angel; Loroño-Pino, María A.; Hopf-Jannasch, Amber S.; Belisle, John T.; Harris, Eva; Blair, Carol D.; Beaty, Barry J.

    2016-01-01

    Background 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. Methodology/Principal Findings 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. Conclusions/Significance These results provide proof-of-concept that a metabolomics approach can be used to identify metabolites or SMBs in serum

  17. Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.

    PubMed

    Bogdan, Maria; Silosi, Isabela; Surlin, Petra; Tica, Andrei Adrian; Tica, Oana Sorina; Balseanu, Tudor-Adrian; Rauten, Anne-Marie; Camen, Adrian

    2015-01-01

    The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination. PMID:26221370

  18. Human Endogenous Retrovirus Type K Antibodies and mRNA as Serum Biomarkers of Early-Stage Breast Cancer

    PubMed Central

    Wang-Johanning, Feng; Li, Ming; Esteva, Francisco J.; Hess, Kenneth R.; Yin, Bingnan; Rycaj, Kiera; Plummer, Joshua B.; Garza, Jeremy G.; Ambs, Stefan; Johanning, Gary L.

    2013-01-01

    A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were employed to detect serum anti-HERV-K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the ROC curve (AUC) of 0.89 (95% confidence interval 0.77 to 1.00) for DCIS and of 0.95 (95% confidence interval 0.89 to 1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV-K(HML-2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease. PMID:23873154

  19. Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats.

    PubMed

    Bogdan, Maria; Silosi, Isabela; Surlin, Petra; Tica, Andrei Adrian; Tica, Oana Sorina; Balseanu, Tudor-Adrian; Rauten, Anne-Marie; Camen, Adrian

    2015-01-01

    The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination.

  20. Salivary and serum biomarkers for the study of side effects of aripiprazole coprescribed with mirtazapine in rats

    PubMed Central

    Bogdan, Maria; Silosi, Isabela; Surlin, Petra; Tica, Andrei Adrian; Tica, Oana Sorina; Balseanu, Tudor-Adrian; Rauten, Anne-Marie; Camen, Adrian

    2015-01-01

    The aim of this study was to investigate whether the co-administration of aripiprazole and mirtazapine could determine weight gain and lipid metabolism disorders in Wistar rats, compared to the same side effects produced by mirtazapine alone, and the risk of hepatotoxicity due to the combination of the two substances. Tumor necrosis factor alpha (TNF-α), liver fatty acid binding protein (L-FABP/FABP1) and repulsive guidance molecule C/hemojuvelin (RGM-C/HJV) levels were determined in serum and in saliva. Also, serum levels for total cholesterol (TC), low and high-density lipoprotein (LDL, HDL), triglycerides (TG), aspartate aminotransferase (ASAT) and alanine amino transferase (ALAT) were assessed. We found positive and statistically significant correlations between serum and salivary levels of TNF-α, L-FABP/FABP1 and RGM-C/HJV. Mirtazapine determined significantly differences of TNF-α and L-FABP serum levels; final body weight; TC and LDL levels, leading to higher concentrations than its association with aripiprazole. Although not statistically significant, mirtazapine group experienced higher values for salivary levels of TNF-α, TG and ASAT, and lower values for HDL, compared to aripiprazole + mirtazapine group. The results suggest that aripiprazole might improve some of the disturbances caused by mirtazapine, and that the two drugs combination cause no additional alterations in liver function. Also, the findings indicate that TNF-α, L-FABP/FABP1 and RGM-C/HJV levels can be helpful as biomarkers for metabolic disturbances and impaired function of hepatocytes, and that their salivary determination can replace serum determination. PMID:26221370

  1. Integrated analysis of numerous heterogeneous gene expression profiles for detecting robust disease-specific biomarkers and proposing drug targets.

    PubMed

    Amar, David; Hait, Tom; Izraeli, Shai; Shamir, Ron

    2015-09-18

    Genome-wide expression profiling has revolutionized biomedical research; vast amounts of expression data from numerous studies of many diseases are now available. Making the best use of this resource in order to better understand disease processes and treatment remains an open challenge. In particular, disease biomarkers detected in case-control studies suffer from low reliability and are only weakly reproducible. Here, we present a systematic integrative analysis methodology to overcome these shortcomings. We assembled and manually curated more than 14,000 expression profiles spanning 48 diseases and 18 expression platforms. We show that when studying a particular disease, judicious utilization of profiles from other diseases and information on disease hierarchy improves classification quality, avoids overoptimistic evaluation of that quality, and enhances disease-specific biomarker discovery. This approach yielded specific biomarkers for 24 of the analyzed diseases. We demonstrate how to combine these biomarkers with large-scale interaction, mutation and drug target data, forming a highly valuable disease summary that suggests novel directions in disease understanding and drug repurposing. Our analysis also estimates the number of samples required to reach a desired level of biomarker stability. This methodology can greatly improve the exploitation of the mountain of expression profiles for better disease analysis.

  2. Serum levels of IL-8 and ICAM-1 as biomarkers for progressive massive fibrosis in coal workers' pneumoconiosis.

    PubMed

    Lee, Jong Seong; Shin, Jae Hoon; Choi, Byung-Soon

    2015-02-01

    Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-α), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF. PMID:25653483

  3. Serum Levels of Annexin A2 as a Candidate Biomarker for Hepatic Fibrosis in Patients With Chronic Hepatitis B

    PubMed Central

    Kolgelier, Servet; Demir, Nazlim Aktug; Inkaya, Ahmet Cagkan; Sumer, Sua; Ozcimen, Serap; Demir, Lutfi Saltuk; Pehlivan, Fatma Seher; Arslan, Mahmure; Arpaci, Abdullah

    2015-01-01

    Background: Hepatologists have studied serologic markers of liver injury for decades. Annexins are a prominent group of such markers and annexin A2 (AnxA2) is one of the best characterized annexins. AnxA2 inhibits HBV polymerase among other functions. Its expression is up-regulated in regenerative hepatocytes. Objectives: To determine if serum AnxA2 level has a role in estimating liver damage in chronic HBV infection and investigate whether AnxA2 levels correlate with hepatic fibrosis. Patients and Methods: This study included 173 patients with chronic hepatitis B (CHB) and 51 healthy controls. Liver fibrosis was graded histologically on liver biopsy samples. Blood samples were taken from patients during biopsy and serum AnxA2 levels were measured with ELISA. Results: In a group of adult patients with CHB, AnxA2 values were far higher than those of the control group (P = 0.001). When we assessed AnxA2 levels based on fibrosis stages, serum AnxA2 levels of patients with early stage fibrosis (stages 1 - 3) were significantly higher than those of patients with advanced stage fibrosis (stages 4 - 5; P = 0.001). Conclusions: AnxA2 is a useful biomarker for early stage fibrosis in patients with CHB. PMID:26587036

  4. Lower serum soluble-EGFR is a potential biomarker for metastasis of HCC demonstrated by N-glycoproteomic analysis.

    PubMed

    Hu, Heng; Gao, Lingling; Wang, Cun; Li, Yan; Ma, Huiying; Chen, Long; Qin, Jie; Liu, Binbin; Liu, Yinkun; Liang, Chunmin

    2015-05-01

    Hepatocellular carcinoma (HCC) is one of the most deadly cancers in the world due to its high metastatic potential. By using the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative N-glycoproteomic analysis, 26 differentially expressed serum glycoproteins derived from defined stages in orthotopic xenograft tumor model were identified. Among them, expression level of soluble EGFR (sEGFR) was verified in HCC cell lines. We found that non-metastasis HCC cell lines express significantly more sEGFR than HCC cell lines with metastasis potential both in cell lysates and culture media. Serum samples from 28 non-metastatic HCC patients and 28 metastatic HCC patients were assayed. Compared with the non-metastatic HCC group, serum level of sEGFR in metastatic HCC group was statistically lower (p<0.01). All these results provide evidence that sEGFR is a potential candidate for metastasis-associated biomarkers of HCC. The related molecular mechanism deserves to be further explored.

  5. Mass spectrometric identification, characterization and validation of the haptoglobin β-chain protein as a lung cancer serum biomarker.

    PubMed

    Ayyub, Asima; Saleem, Mahjabeen; Musharraf, Syed Ghulam; Naz, Mamoona; Tariq, Asma; Hashmi, Naghma

    2015-09-01

    Lung cancer is the major contributor to overall cancer-related mortality. Biomarkers are important in early detection and prognosis, in addition to developing treatment regimes, which may improve the patient survival rates. Biomarkers may also assist in investigating the in depth metabolic pathways and in establishing a set of therapeutic agents leading to early detection of the disease. The present study was designed to identify and confirm a lung cancer protein biomarker and to correlate the differential expression of the protein to a particular histological disease type. A total of 100 lung cancer patients and 50 healthy controls were included in the present study and were categorized into the two main histological types of lung cancer; non‑small cell lung cancer (NSCLC; n=88) and small cell lung cancer (SCLC; n=12). NSCLC was further subclassified into three histological types; adenocarcinoma (n=34), squamous cell carcinoma (n=48) and large cell carcinoma (n=6). The patient and control serum samples underwent sodium dodecyl sulphate polyacrylamide gel electrophoresis characterization followed by two‑dimensional gel electrophoresis. Following mass spectrometry, human haptoglobin was identified with a mass of ~42‑46 kDa and an isoelectric point (pI) of ~5.5‑6.2. The experimental mass of the protein was found to be 45.8 kDa with a pI of 6.13. The matrix‑assisted laser desorption/ionization time‑of‑flight/time‑of‑flight data exhibited spectral peaks of 1146.134, 1724.191, 1345.339 and 2210.319 m/z and Mascot search analysis identified these peaks as haptoglobin (accession no. P00738; Mascot score 87; sequence coverage 23%). This protein was significantly overexpressed in squamous cell carcinoma and adenocarcinoma, as compared with the control. The present study described differentially expressed human haptoglobin as a lung cancer serum protein biomarker, which may serve as a diagnostic and therapeutic target and set a standard criteria for the

  6. Mass Spectrometry-Based Serum and Plasma Peptidome Profiling for Prediction of Treatment Outcome in Patients With Solid Malignancies

    PubMed Central

    Labots, Mariette; Schütte, Lisette M.; van der Mijn, Johannes C.; Pham, Thang V.; Jiménez, Connie R.

    2014-01-01

    Introduction. Treatment selection tools are needed to enhance the efficacy of targeted treatment in patients with solid malignancies. Providing a readout of aberrant signaling pathways and proteolytic events, mass spectrometry-based (MS-based) peptidomics enables identification of predictive biomarkers, whereas the serum or plasma peptidome may provide easily accessible signatures associated with response to treatment. In this systematic review, we evaluate MS-based peptide profiling in blood for prompt clinical implementation. Methods. PubMed and Embase were searched for studies using a syntax based on the following hierarchy: (a) blood-based matrix-assisted or surface-enhanced laser desorption/ionization time-of-flight MS peptide profiling (b) in patients with solid malignancies (c) prior to initiation of any treatment modality, (d) with availability of outcome data. Results. Thirty-eight studies were eligible for review; the majority were performed in patients with non-small cell lung cancer (NSCLC). Median classification prediction accuracy was 80% (range: 66%–93%) in 11 models from 14 studies reporting an MS-based classification model. A pooled analysis of 9 NSCLC studies revealed clinically significant median progression-free survival in patients classified as “poor outcome” and “good outcome” of 2.0 ± 1.06 months and 4.6 ± 1.60 months, respectively; median overall survival was also clinically significant at 4.01 ± 1.60 months and 10.52 ± 3.49 months, respectively. Conclusion. Pretreatment MS-based serum and plasma peptidomics have shown promising results for prediction of treatment outcome in patients with solid tumors. Limited sample sizes and absence of signature validation in many studies have prohibited clinical implementation thus far. Our pooled analysis and recent results from the PROSE study indicate that this profiling approach enables treatment selection, but additional prospective studies are warranted. PMID:25187478

  7. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions

    PubMed Central

    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

  8. Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions.

    PubMed

    Voorwald, Fabiana Azevedo; Marchi, Fabio Albuquerque; Villacis, Rolando Andre Rios; Alves, Carlos Eduardo Fonseca; Toniollo, Gilson Hélio; Amorim, Renee Laufer; Drigo, Sandra Aparecida; Rogatto, Silvia Regina

    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

  9. Serum lipid & lipoprotein profiles of obese Chinese children.

    PubMed

    Ho, T F; Paramsothy, S; Aw, T C; Yip, W C

    1996-03-01

    The serum lipid and lipoprotein levels of 59 obese Chinese children with a mean age of 13.0 years and mean relative weight of 164.2% were analysed. Between 40% to 54% of these children had elevated lipid and lipoprotein levels and about 78% had reduced high density lipoprotein (HDL) level when compared to healthy American and Japanese children. The obese children also had higher mean levels of total cholesterol (TC) and lower HDL compared to male adults in the local population. Those with elevated TC had higher mean relative weight (170% vs 159%, p < 0.05). In view of the close association between hyperlipidaemia and atherosclerosis, obese children should be carefully screened and managed to prevent long term morbidity and mortality of coronary artery disease. PMID:10967982

  10. Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma

    SciTech Connect

    Nomura, Fumio; Sogawa, Kazuyuki; Noda, Kenta; Seimiya, Masanori; Matsushita, Kazuyuki; Miura, Toshihide; Tomonaga, Takeshi; Yoshitomi, Hideyuki; Imazeki, Fumio; Takizawa, Hirotaka; Mogushi, Kaoru; Miyazaki, Masaru; Yokosuka, Osamu

    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.

  11. Serum Trace Element Profiles, Prolactin, and Cortisol in Transient Ischemic Attack Patients.

    PubMed

    Klimenko, Lydmila L; Skalny, Anatoly V; Turna, Aliya A; Tinkov, Alexey A; Budanova, Maria N; Baskakov, Ivan S; Savostina, Marina S; Mazilina, Aksana N; Deev, Anatoly I; Nikonorov, Alexandr A

    2016-07-01

    The primary aim of the present study was to assess the association between trace element status, brain damage biomarkers, cortisol, and prolactin levels in transient ischemic attack (TIA) patients. Ten male and 10 female TIA patients were involved in this study. Age, gender, and BMI-matched volunteers served as the respective control group. Serum samples were examined for complement components C4 and C3a, vascular endothelial growth factor (VEGF), S100B, NR2 antibodies (NR2Ab), total antioxidant status (TAS), cortisol, and prolactin. Trace element concentration in serum samples was assessed using inductively coupled plasma mass spectrometry at NexION 300D. The obtained data indicate that both male and female TIA patients were characterized by the increased C4 and prolactin concentrations. At the same time, serum VEGF levels were elevated in only men, whereas TAS values were decreased in women with TIA. Serum cortisol concentrations were significantly increased only in female TIA patients. Men and women with TIA were characterized by a 32 and 44 % decrease in serum Fe content. A two- and threefold increase in serum V content was observed in TIA females and males, respectively. Women with TIA had 60 % higher values of serum B, whereas male patients were characterized by a sevonfold increase in boron content in comparison to the control values. TIA also resulted in decreased serum Cu content in women and elevation of I, Li, Mn, Se, Zn, As, Pb, Ni, and Sr levels in men. Correlation analysis revealed a significant association between trace elements concentration and the studied parameters.

  12. Effects of a 7-day military training exercise on inflammatory biomarkers, serum hepcidin, and iron status

    PubMed Central

    2013-01-01

    Background Hepcidin, a peptide that is released into the blood in response to inflammation, prevents cellular iron export and results in declines in iron status. Elevated serum and urinary levels of hepcidin have been observed in athletes following exercise, and declines in iron status have been reported following prolonged periods of training. The objective of this observational study was to characterize the effects of an occupational task, military training, on iron status, inflammation, and serum hepcidin. Findings Volunteers (n = 21 males) included Norwegian Soldiers participating in a 7-day winter training exercise that culminated in a 3-day, 54 km ski march. Fasted blood samples were collected at baseline, on day 4 (PRE, prior to the ski march), and again on day 7 (POST, following the ski march). Samples were analyzed for hemoglobin, serum ferritin, soluble transferrin receptor (sTfR), interleukin-6 (IL-6), and serum hepcidin. Military training affected inflammation and serum hepcidin levels, as IL-6 and hepcidin concentrations increased (P < 0.05) from the baseline to POST (mean ± SD, 9.1 ± 4.9 vs. 14.5 ± 8.4 pg/mL and 6.5 ± 3.5 vs. 10.2 ± 6.9 ng/mL, respectively). Iron status was not affected by the training exercise, as sTfR levels did not change over the course of the 7-day study. Conclusions Military training resulted in significant elevations in IL-6 and serum hepcidin. Future studies should strive to identify the role of hepcidin in the adaptive response to exercise, as well as countermeasures for the prevention of chronic or repeated elevations in serum hepcidin due to exercise or sustained occupational tasks which may result in longer term decrements in iron status. PMID:24188143

  13. Serum glial fibrillary acidic protein as a diagnostic biomarker in dogs with progressive myelomalacia.

    PubMed

    Sato, Yasunori; Shimamura, Shunsuke; Mashita, Tadahisa; Kobayashi, Saori; Okamura, Yasuhiko; Katayama, Masaaki; Kamishina, Hiroaki; Sato, Reeko; Uzuka, Yuji; Yasuda, Jun

    2013-07-31

    In humans, increased levels of GFAP in the CSF and blood have been reported with various neural diseases. However, there has been no study describing the usefulness of GFAP in the blood for disease of the spinal cord in dogs. The aim of this study was to describe the utility of GFAP in serum for a diagnosis of progressive myelomalacia. Fifty-six dogs with acute thoracolumbar IVDD diagnosed by computed tomography with myelography or MRI were included. Serum specimens were collected at initial presentation from all cases and at follow-up examinations from some cases. Serum samples were assayed for GFAP concentrations using a commercially available GFAP ELISA Kit. Progressive myelomalacia was the final diagnosis in 8/51 cases (15.6%). Eight dogs had clinical signs suggestive of progressive myelomalacia, of which 6 were positive and 2 were negative by GFAP. Seven dogs had a detectable level of serum GFAP, of which 6 had the onset of progressive myelomalacia. The sensitivity and specificity of the GFAP to progressive myelomalacia were 75% and 97.7%, respectively. The results suggest the utility of GFAP in serum in the diagnosis of progressive myelomalacia.

  14. Validation of biomarkers of CVD risk from dried blood spots in community-based research: Methodologies and study-specific serum equivalencies

    PubMed Central

    Samuelsson, Laura B.; Hall, Martica H.; McLean, Shakir; Porter, James H.; Berkman, Lisa; Marino, Miguel; Sembajwe, Grace; McDade, Thomas W.; Buxton, Orfeu M.

    2016-01-01

    Objective Dried blood spot (DBS) methodology offers significant advantages over venipuncture in vulnerable populations or large-scale studies, including reduced participant burden and higher response rates. Uncertainty about validity of cardiovascular risk biomarkers remains a barrier to wide-scale use. We determined the validity of DBS-derived biomarkers of CVD risk versus gold-standard assessments, and study-specific, serum-equivalency values for clinical relevance of DBS-derived values. Methods Concurrent venipuncture serum and DBS samples (n=150 adults) were assayed in CLIA-certified and DBS laboratories, respectively. Time controls of DBS standard samples were assayed single-blind along with test samples. Linear regression analyses evaluated DBS-to-serum equivalency values; agreement and bias were assessed via Bland-Altman plots. Results Linear regressions of venipuncture values on DBS-to-serum equivalencies provided R2 values for TC, HDL-C, CRP of 0.484, 0.118, 0.666, respectively. Bland-Altman plots revealed minimal systematic bias between DBS-to-serum and venipuncture values; precision worsened at higher mean values of CRP. Time controls reveal little degradation or change in analyte values for HDL-C and CRP over 30 weeks. Conclusions DBS-assessed biomarkers represent a valid alternative to venipuncture assessments. Large studies using DBS should include study-specific serum-equivalency determinations to optimize individual-level sensitivity, viability of detecting intervention effects, and generalizability in community-level, primary prevention interventions. PMID:26652683

  15. Association between urinary biomarkers of exposure to organophosphate insecticides and serum reproductive hormones in men from NHANES 1999–2002

    PubMed Central

    Omoike, Ogbebor; Lewis, Ryan C.; Meeker, John D.

    2015-01-01

    Exposure to organophosphate (OP) insecticides may alter reproductive hormone levels in men and increase the risk for poor reductive health and other adverse health outcomes. However, relevant epidemiology studies in men are limited. We evaluated urinary concentrations of OP metabolites (3,5,6-trichloro-2-pyridinol and six dialkyl phosphates) in relation to serum concentrations of testosterone (T) and estradiol among 356 men aged 20–55 years old from the U.S. National Health and Nutrition Examination Survey. Biomarkers were detected in greater than 50% of the samples, except for diethyldithiophosphate, dimethylphosphate, and dimethyldithiophosphate. In adjusted regression models, we observed a statistically significant inverse relationship between diethyl phosphate (DEP) and T when DEP was modeled as either a continuous or categorical variable. These findings add to the limited evidence that exposure to certain OP insecticides is linked to altered T in men, which may have important implications for male health. PMID:25908234

  16. Serum IL-18 as biomarker in predicting long-term renal outcome among pediatric-onset systemic lupus erythematosus patients

    PubMed Central

    Wu, Chao-Yi; Yang, Huang-Yu; Yao, Tsung-Chieh; Liu, Su-Hsun; Huang, Jing-Long

    2016-01-01

    Abstract An urge of biomarker identification is needed to better monitor lupus nephritis (LN) disease activity, guide clinical treatment, and predict patient's long-term outcome. With the proinflammatory effect and its association with inflammasomes, the significance of interleukin-18 (IL-18) among pediatric-onset systemic lupus erythematous (pSLE) patient, especially, its importance in predicting long-term renal outcome was investigated. In a pSLE cohort of 96 patients with an average follow-up period of 10.39 ± 3.31 years, clinical data and laboratory workups including serum IL-18 were collected at time of disease onset and 6 months after treatment despite their initial renal status. Through Cox regression analysis, the parameters at baseline and at 6 months posttreatment were carefully analyzed. Average age of all cases was 12.74 ± 3.01 years old and 65 of them underwent renal biopsy at the time of diagnosis. Nine subjects (9.38%) progressed to end-stage renal disease (ESRD) and 2 cases (2.08%) died during follow-up. Through multivariate analysis, serum IL-18 level 6 months posttreatment was found to be the most unfavorable factor associating poor clinical outcome despite patient's initial renal status. In addition, the presentation of serum IL-18 in its correlation with SLE global disease activity as well as the presence and severity of LN were all significant (P < 0.001, P = 0.03, and P = 0.02, respectively). The histological classification of LN, however, was not associated with the level of IL-18 among the pSLE patients (P = 0.64). The role of serum IL-18 as biomarker representing global disease activity and status of renal flares among pSLE population was shown for the first time. Additionally, we have identified IL-18 at 6 months posttreatment a novel marker for long-term renal outcome prediction. PMID:27749566

  17. A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

    PubMed

    Calderon, C; Zucht, H D; Kuhn, A; Wozniacka, A; Szepietowski, J C; Nyberg, F; Weichenthal, M; Piantone, A; Budde, P

    2015-11-01

    Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE.

  18. A multicenter photoprovocation study to identify potential biomarkers by global peptide profiling in cutaneous lupus erythematosus.

    PubMed

    Calderon, C; Zucht, H D; Kuhn, A; Wozniacka, A; Szepietowski, J C; Nyberg, F; Weichenthal, M; Piantone, A; Budde, P

    2015-11-01

    Cutaneous lupus erythematosus (CLE) is an inflammatory autoimmune skin disease in which abnormal photosensitivity is an important pathogenetic factor but is difficult to predict, creating a challenge in determining treatment efficacy. Although photosensitivity in CLE patients may change over time, photoprovocation testing with ultraviolet (UV) A and UVB irradiation can be a helpful tool to explore differences between responders and nonresponders during photoprovocation. To identify biomarkers that could substitute for the clinical endpoint lesion development, we performed a global peptidomics profiling analysis of CLE subjects in a controlled photoprovocation study. Plasma and skin biopsy samples were collected before and after UV-irradiation from 13 healthy volunteers and 47 CLE subjects. Twenty-two of the 47 CLE subjects developed skin lesions. The samples were analyzed using a label-free quantitative peptidomics workflow combined with univariate and multivariate statistical analyses. The primary finding was identification of a specific plasma peptide signature separating responders versus nonresponders at baseline. The peptide signature consisted of beta 2-microglobulin (B2MG), human beta-defensin-1, and peptides derived from CD99, polymeric immunoglobulin receptor, and immunoglobulin kappa light chains. In skin, elevated B2MG levels correlated with lesion formation. Our results show that the peptidome is a rich source of potential biomarkers for predicting photosensitivity in CLE. PMID:26206719

  19. Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

    NASA Astrophysics Data System (ADS)

    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. Perspectives on a combined test of multi serum biomarkers in China: towards screening for and diagnosing hepatocellular carcinoma at an earlier stage.

    PubMed

    Zhang, Keming; Song, Peipei; Gao, Jianjun; Li, Gaohua; Zhao, Xin; Zhang, Shaogeng

    2014-06-01

    China has 50% of the worldwide hepatocellular carcinoma (HCC) cases, and the HBV-related cases accounts for approximately 85%. Over the past few decades, although a series of standardized management methods for HCC has been implemented in China, most HCC patient in China still suffered from advanced-stage disease, in consequence, reducing the opportunity of curable treatment that can be offered to achieve long-term disease-free survival for HCC patient. Accordingly, strategies including screening and diagnose HCC at an earlier stage are urgently needed in China. In this study, the current status, challenges, and prospects of early detection of HCC in China have been analyzed. The result indicated the need for using multi serum biomarkers for early HCC detection. During the past ten years, the research on the clinical usefulness of novel serum biomarkers of des-γ-carboxy-prothrombin (DCP), Dickkopf-1 (DKK1) and Midkine (MDK) in early HCC detection for Chinese patients found that the novel serum biomarker can complete the measurement of α-fetoprotein (AFP) in the diagnosis process of HCC, particularly for the patient with negative AFP with/or at an early stage. More large-scale, multi-center studies are expected to be performed in China to provide further evidence, and using novel and reliable serum biomarkers to complement AFP as a new trend is expected to be extensively used in clinical practice to facilitate early detection for those patients with HCC in China.

  1. Detection of a Serum Siderophore by LC-MS/MS as a Potential Biomarker of Invasive Aspergillosis

    PubMed Central

    Carroll, Cassandra S.; Amankwa, Lawrence N.; Pinto, Linda J.; Fuller, Jeffrey D.; Moore, Margo M.

    2016-01-01

    Invasive aspergillosis (IA) is a life-threatening systemic mycosis caused primarily by Aspergillus fumigatus. Early diagnosis of IA is based, in part, on an immunoassay for circulating fungal cell wall carbohydrate, galactomannan (GM). However, a wide range of sensitivity and specificity rates have been reported for the GM test across various patient populations. To obtain iron in vivo, A. fumigatus secretes the siderophore, N,N',N"-triacetylfusarinine C (TAFC) and we hypothesize that TAFC may represent a possible biomarker for early detection of IA. We developed an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for TAFC analysis from serum, and measured TAFC in serum samples collected from patients at risk for IA. The method showed lower and upper limits of quantitation (LOQ) of 5 ng/ml and 750 ng/ml, respectively, and complete TAFC recovery from spiked serum. As proof of concept, we evaluated 76 serum samples from 58 patients with suspected IA that were investigated for the presence of GM. Fourteen serum samples obtained from 11 patients diagnosed with probable or proven IA were also analyzed for the presence of TAFC. Control sera (n = 16) were analyzed to establish a TAFC cut-off value (≥6 ng/ml). Of the 36 GM-positive samples (≥0.5 GM index) from suspected IA patients, TAFC was considered positive in 25 (69%). TAFC was also found in 28 additional GM-negative samples. TAFC was detected in 4 of the 14 samples (28%) from patients with proven/probable aspergillosis. Log-transformed TAFC and GM values from patients with proven/probable IA, healthy individuals and SLE patients showed a significant correlation with a Pearson r value of 0.77. In summary, we have developed a method for the detection of TAFC in serum that revealed this fungal product in the sera of patients at risk for invasive aspergillosis. A prospective study is warranted to determine whether this method provides improved early detection of IA. PMID:26974544

  2. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    SciTech Connect

    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. Protein Profiling of Human Breast Tumor Cells Identifies Novel Biomarkers Associated with Molecular Subtypes*S⃞

    PubMed Central

    Gonçalves, Anthony; Charafe-Jauffret, Emmanuelle; Bertucci, François; Audebert, Stéphane; Toiron, Yves; Esterni, Benjamin; Monville, Florence; Tarpin, Carole; Jacquemier, Jocelyne; Houvenaeghel, Gilles; Chabannon, Christian; Extra, Jean-Marc; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel

    2008-01-01

    Molecular subtypes of breast cancer with relevant biological and clinical features have been defined recently, notably ERBB2-overexpressing, basal-like, and luminal-like subtypes. To investigate the ability of mass spectrometry-based proteomics technologies to analyze the molecular complexity of human breast cancer, we performed a SELDI-TOF MS-based protein profiling of human breast cell lines (BCLs). Triton-soluble proteins from 27 BCLs were incubated with ProteinChip arrays and subjected to SELDI analysis. Unsupervised global hierarchical clustering spontaneously discriminated two groups of BCLs corresponding to “luminal-like” cell lines and to “basal-like” cell lines, respectively. These groups of BCLs were also different in terms of estrogen receptor status as well as expression of epidermal growth factor receptor and other basal markers. Supervised analysis revealed various protein biomarkers with differential expression in basal-like versus luminal-like cell lines. We identified two of them as a carboxyl terminus-truncated form of ubiquitin and S100A9. In a small series of frozen human breast tumors, we confirmed that carboxyl terminus-truncated ubiquitin is observed in primary breast samples, and our results suggest its higher expression in luminal-like tumors. S100A9 up-regulation was found as part of the transcriptionally defined basal-like cluster in DNA microarrays analysis of human tumors. S100A9 association with basal subtypes as well as its poor prognosis value was demonstrated on a series of 547 tumor samples from early breast cancer deposited in a tissue microarray. Our study shows the potential of integrated genomics and proteomics profiling to improve molecular knowledge of complex tumor phenotypes and identify biomarkers with valuable diagnostic or prognostic values. PMID:18426791

  4. Urine and serum microRNA-1 as novel biomarkers for myocardial injury in open-heart surgeries with cardiopulmonary bypass.

    PubMed

    Zhou, Xian; Mao, Anqiong; Wang, Xiaobin; Duan, Xiaoxia; Yao, Yi; Zhang, Chunxiang

    2013-01-01

    MicroRNA-1 (miR-1) is a cardio-specific/enriched microRNA. Our recent studies have revealed that serum and urine miR-1 could be a novel sensitive biomarker for acute myocardial infarction. Open-heart surgeries with cardiopulmonary bypass (CPB) are often accompanied with surgery injury and CPB-associated injury on the hearts. However, the association of miR-1 and these intra-operative and post-operative cardiac injures is unknown. The objective of this study was to test the hypothesis that urine and serum miR-1 might be a novel biomarker for myocardial injuries in open-heart surgeries with CPB. Serum and urine miR-1 levels in 20 patients with elective mitral valve surgery were measured at pre-surgery, pre-CPB, 60 min post-CBP, and 24h post-CBP. Serum cardiac troponin-I (cTnI) was used as a positive control biomarker for cardiac injury. Compared with these in pre-operative and pre-CPB groups, the levels of miR-1 in serum and urine from patients after open-heart surgeries and CPB were significant increased at all observed time points. A similar pattern of serum cTnI levels and their strong positive correlation with miR-1 levels were identified in these patients. The results suggest that serum and urine miR-1 may be a novel sensitive biomarker for myocardial injury in open-heart surgeries with CPB.

  5. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation.

    PubMed

    Moen, Aurora; Lind, Anne-Li; Thulin, Måns; Kamali-Moghaddam, Masood; Røe, Cecilie; Gjerstad, Johannes; Gordh, Torsten

    2016-01-01

    Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ullevål, Norway, during the period 2007-2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation. PMID:27293953

  6. Inflammatory Serum Protein Profiling of Patients with Lumbar Radicular Pain One Year after Disc Herniation

    PubMed Central

    Moen, Aurora; Lind, Anne-Li; Thulin, Måns; Kamali-Moghaddam, Masood; Røe, Cecilie; Gordh, Torsten

    2016-01-01

    Earlier studies suggest that lumbar radicular pain following disc herniation may be associated with a local or systemic inflammatory process. In the present study, we investigated the serum inflammatory protein profile of such patients. All 45 patients were recruited from Oslo University Hospital, Ullevål, Norway, during the period 2007–2009. The new multiplex proximity extension assay (PEA) technology was used to analyze the levels of 92 proteins. Interestingly, the present data showed that patients with radicular pain 12 months after disc herniation may be different from other patients with regard to many measurable serum cytokines. Given a false discovery rate (FDR) of 0.10 and 0.05, we identified 41 and 13 proteins, respectively, which were significantly upregulated in the patients with severe pain one year after disc herniation. On the top of the list ranked by estimated increase we found C-X-C motif chemokine 5 (CXCM5; 217% increase), epidermal growth factor (EGF; 142% increase), and monocyte chemotactic protein 4 (MCP-4; 70% increase). Moreover, a clear overall difference in the serum cytokine profile between the chronic and the recovered patients was demonstrated. Thus, the present results may be important for future protein serum profiling of lumbar radicular pain patients with regard to prognosis and choice of treatment. We conclude that serum proteins may be measurable molecular markers of persistent pain after disc herniation. PMID:27293953

  7. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men.

    PubMed

    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.

  8. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis

    PubMed Central

    Ryu, Moon-Suhn; Langkamp-Henken, Bobbi; Chang, Shou-Mei; Shankar, Meena N.; Cousins, Robert J.

    2011-01-01

    Implementation of zinc interventions for subjects suspected of being zinc-deficient is a global need, but is limited due to the absence of reliable biomarkers. To discover molecular signatures of human zinc deficiency, a combination of transcriptome, cytokine, and microRNA analyses was applied to a dietary zinc depletion/repletion protocol with young male human subjects. Concomitant with a decrease in serum zinc concentration, changes in buccal and blood gene transcripts related to zinc homeostasis occurred with zinc depletion. Microarray analyses of whole blood RNA revealed zinc-responsive genes, particularly, those associated with cell cycle regulation and immunity. Responses of potential signature genes of dietary zinc depletion were further assessed by quantitative real-time PCR. The diagnostic properties of specific serum microRNAs for dietary zinc deficiency were identified by acute responses to zinc depletion, which were reversible by subsequent zinc repletion. Depression of immune-stimulated TNFα secretion by blood cells was observed after low zinc consumption and may serve as a functional biomarker. Our findings introduce numerous novel candidate biomarkers for dietary zinc status assessment using a variety of contemporary technologies and which identify changes that occur prior to or with greater sensitivity than the serum zinc concentration which represents the current zinc status assessment marker. In addition, the results of gene network analysis reveal potential clinical outcomes attributable to suboptimal zinc intake including immune function defects and predisposition to cancer. These demonstrate through a controlled depletion/repletion dietary protocol that the illusive zinc biomarker(s) can be identified and applied to assessment and intervention strategies. PMID:22171008

  9. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis.

    PubMed

    Ryu, Moon-Suhn; Langkamp-Henken, Bobbi; Chang, Shou-Mei; Shankar, Meena N; Cousins, Robert J

    2011-12-27

    Implementation of zinc interventions for subjects suspected of being zinc-deficient is a global need, but is limited due to the absence of reliable biomarkers. To discover molecular signatures of human zinc deficiency, a combination of transcriptome, cytokine, and microRNA analyses was applied to a dietary zinc depletion/repletion protocol with young male human subjects. Concomitant with a decrease in serum zinc concentration, changes in buccal and blood gene transcripts related to zinc homeostasis occurred with zinc depletion. Microarray analyses of whole blood RNA revealed zinc-responsive genes, particularly, those associated with cell cycle regulation and immunity. Responses of potential signature genes of dietary zinc depletion were further assessed by quantitative real-time PCR. The diagnostic properties of specific serum microRNAs for dietary zinc deficiency were identified by acute responses to zinc depletion, which were reversible by subsequent zinc repletion. Depression of immune-stimulated TNFα secretion by blood cells was observed after low zinc consumption and may serve as a functional biomarker. Our findings introduce numerous novel candidate biomarkers for dietary zinc status assessment using a variety of contemporary technologies and which identify changes that occur prior to or with greater sensitivity than the serum zinc concentration which represents the current zinc status assessment marker. In addition, the results of gene network analysis reveal potential clinical outcomes attributable to suboptimal zinc intake including immune function defects and predisposition to cancer. These demonstrate through a controlled depletion/repletion dietary protocol that the illusive zinc biomarker(s) can be identified and applied to assessment and intervention strategies.

  10. Neighborhood Socioeconomic Status in Relation to Serum Biomarkers in the Black Women's Health Study.

    PubMed

    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. PMID:27000125

  11. [Features of diurnal profile of blood pressure in workers having serum aromatic hydrocarbons level].

    PubMed

    Baĭdina, A S; Safonova, M A; Alekseev, V B

    2012-01-01

    Features of diurnal profile of blood pressure in workers having serum level of benzol and ethylbenzene are high systolic and diastolic arterial blood pressure during the day, index of systolic arterial pressure time and index diastolic arterial pressure time was also high. These features should be considered in anti-hypertensives prescription.

  12. Human Ozone (O3) Exposure Alters Serum Profile of Lipid Metabolites

    EPA Science Inventory

    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...

  13. The usefulness of biomarkers of alcohol abuse in hair and serum carbohydrate-deficient transferrin: a case report.

    PubMed

    De Giovanni, Nadia; Cittadini, Francesca; Martello, Simona

    2015-08-01

    The detection of carbohydrate-deficient transferrin (CDT) in serum is widely accepted to identify chronic alcohol consumption over the previous two weeks, but minor ethanol metabolites detected in hair often complete the information obtained. In particular, ethylglucuronide and cocaethylene (a marker of simultaneous intake of cocaine and alcohol) allow correct interpretation of data obtained in forensic cases. We refer to a negative CDT value obtained from a serum sample collected during hospitalization of a man admitted for cardiac arrest who died about 14 h later. Clinical analysis performed on admission showed a high ethanol level and a positive urinary screening for cocaine. The toxicological analyses of post-mortem samples found cocaine metabolites in his urine and blood. The negative CDT level suggested the ethanol concentration at admission to be an acute episode. Cocaine and cocaethylene well above the cut-off suggested by the literature were found in hair analyzed for the entire length (about 1 cm). Ethylglucuronide detected on the same hair sample confirmed chronic abuse of ethanol in the previous month, at least. The present report suggests caution in the interpretation of biomarkers of alcohol abuse, encouraging the detection of more than one marker to avoid misinterpretation. PMID:25557913

  14. Serum Procalcitonin and Procalcitonin Clearance as a Prognostic Biomarker in Patients with Severe Sepsis and Septic Shock.

    PubMed

    Huang, Min-Yi; Chen, Chun-Yu; Chien, Ju-Huei; Wu, Kun-Hsi; Chang, Yu-Jun; Wu, Kang-Hsi; Wu, Han-Ping

    2016-01-01

    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. PMID:27088084

  15. Estimation of Salivary and Serum Biomarkers in Diabetic and Non Diabetic Patients - A Comparative Study

    PubMed Central

    Ladgotra, Amit; Raj, Seetharamaiah Sunder

    2016-01-01

    Introduction Blood is the gold standard body fluid for diagnosis of Diabetes Mellitus (DM) but saliva offers an alternative to serum as a biological fluid for diagnostic purposes because it contains serum constituents. Aim The study was conducted to estimate and compare serum and salivary glucose, amylase, proteins, calcium and phosphorus levels in DM and healthy subjects and to evaluate whether saliva can be used as a diagnostic fluid in DM patients. Materials and Methods Study consisted of 120 subjects from OPD of Surendera Dental College, Sriganganagar, Rajasthan, India. The study groups were divided into Group I-60 DM patients (Type I & II) and Group II-60 healthy subjects. The saliva and serum samples were collected from each subject and levels of different biochemical parameters were estimated. Results Mean serum level of glucose (211.50 ± 43.82), amylase (79.86 ± 16.23), total proteins (6.65 ± 0.84), calcium (7.17 ± 0.91) and phosphorus (3.68±0.65) as observed in Group I while in Group II, glucose (88.81±11.29), amylase (77.67±14.88), total proteins (6.35±0.76), calcium (7.52±0.97) and phosphorus (3.96 ± 0.91) were noted. Mean salivary level of glucose (14.10±6.99), amylase (1671.42±569.86), total proteins (1.33±1.11), calcium (10.06±2.76) and phosphorus (13.75±4.45) as observed in Group I while in Group II, glucose (5.87± 2.42), amylase (1397.59 ±415.97), total proteins (1.36±0.81), calcium (7.73±2.78) and phosphorus (8.39 ± 1.95) were noted. On comparing values in saliva and serum, among two groups, an insignificant difference (p>0.005) was found between few of them. Conclusion Values regarding blood and salivary biochemical parameters were distinctly different between two groups suggesting salivary parameters can be used as a diagnostic alternative to blood parameters for diabetes mellitus. PMID:27504412

  16. Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

    PubMed

    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.

  17. Serum chemistry and lipid profiles in neonatal beagle puppies fed homemade milk replacer formulas.

    PubMed

    Chandler, M L; Miller, E; Olson, P N; Ralston, S L

    1993-04-01

    Milk replacer formulas based on cow's milk and egg yolks are frequently recommended for use in neonatal puppies. These formulas are lower in protein, kilocalories, calcium, and phosphorus than bitch's milk. In addition, the cholesterol content is greater than bitch's milk. The effect of feeding these formulas on serum chemistry profiles, lipid profiles, and alkaline phosphatase isoenzyme profiles of 5-week-old beagle puppies was studied. Three groups of beagle puppies were fed bitch's milk (control) (n = 18), a homemade milk-egg-oil formula (Formula 1) (n = 18), or a homemade milk-egg-oil formula supplemented with additional calcium and phosphorous (Formula 2) (n = 18). Concentrations of serum urea nitrogen, albumin, and total CO2 were lower (P < 0.05), and concentrations of serum phosphorus, globulins, sodium, chloride, and cholesterol were higher (P < 0.05) in formula-fed puppies than bitch-fed puppies. Serum potassium concentration was lower in the puppies fed Formula 1 than in the control puppies (P < 0.05), and serum potassium concentration in the puppies fed Formula 2 was not significantly different from that in puppies fed Formula 1 or the control puppies. Total triglyceride (TG) and high density lipoprotein2 cholesterol (HDL2) concentrations were similar in all three groups of puppies but the combined high density lipoprotein1 (HDL1) plus low density lipoprotein (LDL) cholesterol fraction was higher (P < 0.05) in the formula-fed puppies and accounted for the majority of the increase in cholesterol. There were no differences (P < 0.05) in total serum alkaline phosphatase (ALP) or bone-derived ALP (BALP) concentrations among the groups, however there was a higher (P < 0.05) serum concentration of liver-derived ALP (LALP) in the Formula 1-fed puppies. Feeding homemade egg and cow's milk-based puppy replacement formulas is not recommended for long term use. PMID:8467696

  18. Identification of Sensitive Serum microRNA Biomarkers for Radiation Biodosimetry

    PubMed Central

    Jacob, Naduparambil Korah; Cooley, James V.; Yee, Tamara N.; Jacob, Jidhin; Alder, Hansjuerg; Wickramasinghe, Priyankara; Maclean, Kirsteen H.; Chakravarti, Arnab

    2013-01-01

    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 during and after

  19. Identification of sensitive serum microRNA biomarkers for radiation biodosimetry.

    PubMed

    Jacob, Naduparambil Korah; Cooley, James V; Yee, Tamara N; Jacob, Jidhin; Alder, Hansjuerg; Wickramasinghe, Priyankara; Maclean, Kirsteen H; Chakravarti, Arnab

    2013-01-01

    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 during and after

  20. Detection of Rheumatoid Arthritis–Interstitial Lung Disease Is Enhanced by Serum Biomarkers

    PubMed Central

    Doyle, Tracy J.; Patel, Avignat S.; Hatabu, Hiroto; Nishino, Mizuki; Wu, Guodong; Osorio, Juan C.; Golzarri, Maria F.; Traslosheros, Andres; Chu, Sarah G.; Frits, Michelle L.; Iannaccone, Christine K.; Koontz, Diane; Fuhrman, Carl; Weinblatt, Michael E.; El-Chemaly, Souheil Y.; Washko, George R.; Hunninghake, Gary M.; Choi, Augustine M. K.; Dellaripa, Paul F.; Oddis, Chester V.; Shadick, Nancy A.; Ascherman, Dana P.

    2015-01-01

    Rationale: Interstitial lung disease (ILD), a leading cause of morbidity and mortality in rheumatoid arthritis (RA), is highly prevalent, yet RA-ILD is underrecognized. Objectives: To identify clinical risk factors, autoantibodies, and biomarkers associated with the presence of RA-ILD. Methods: Subjects enrolled in Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study (BRASS) and American College of Rheumatology (ACR) cohorts were evaluated for ILD. Regression models were used to assess the association between variables of interest and RA-ILD. Receiver operating characteristic curves were generated in BRASS to determine if a combination of clinical risk factors and autoantibodies can identify RA-ILD and if the addition of investigational biomarkers is informative. This combinatorial signature was subsequently tested in ACR. Measurements and Main Results: A total of 113 BRASS subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 ACR subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen for both clinically evident and subclinical RA-ILD. Conclusions: Clinical risk factors and autoantibodies are strongly associated with the presence of clinically evident and subclinical RA-ILD on computed tomography scan in two independent RA cohorts. A biomarker signature composed of matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant

  1. Serum clara cell protein: a sensitive biomarker of increased lung epithelium permeability caused by ambient ozone.

    PubMed

    Broeckaert, F; Arsalane, K; Hermans, C; Bergamaschi, E; Brustolin, A; Mutti, A; Bernard, A

    2000-06-01

    Ozone in ambient air may cause various effects on human health, including decreased lung function, asthma exacerbation, and even premature mortality. These effects have been evidenced using various clinical indicators that, although sensitive, do not specifically evaluate the O(3)-increased lung epithelium permeability. In the present study, we assessed the acute effects of ambient O(3) on the pulmonary epithelium by a new approach relying on the assay in serum of the lung-specific Clara cell protein (CC16 or CC10). We applied this test to cyclists who exercised for 2 hr during episodes of photochemical smog and found that O(3) induces an early leakage of lung Clara cell protein. The protein levels increased significantly into the serum from exposure levels as low as 0.060-0.084 ppm. Our findings, confirmed in mice exposed to the current U.S. National Ambient Air Quality Standards for O(3) (0.08 ppm for 8 hr) indicate that above the present natural background levels, there is almost no safety margin for the effects of ambient O(3) on airway permeability. The assay of CC16 in the serum represents a new sensitive noninvasive test allowing the detection of early effects of ambient O(3) on the lung epithelial barrier. PMID:10856027

  2. Serum clara cell protein: a sensitive biomarker of increased lung epithelium permeability caused by ambient ozone.

    PubMed Central

    Broeckaert, F; Arsalane, K; Hermans, C; Bergamaschi, E; Brustolin, A; Mutti, A; Bernard, A

    2000-01-01

    Ozone in ambient air may cause various effects on human health, including decreased lung function, asthma exacerbation, and even premature mortality. These effects have been evidenced using various clinical indicators that, although sensitive, do not specifically evaluate the O(3)-increased lung epithelium permeability. In the present study, we assessed the acute effects of ambient O(3) on the pulmonary epithelium by a new approach relying on the assay in serum of the lung-specific Clara cell protein (CC16 or CC10). We applied this test to cyclists who exercised for 2 hr during episodes of photochemical smog and found that O(3) induces an early leakage of lung Clara cell protein. The protein levels increased significantly into the serum from exposure levels as low as 0.060-0.084 ppm. Our findings, confirmed in mice exposed to the current U.S. National Ambient Air Quality Standards for O(3) (0.08 ppm for 8 hr) indicate that above the present natural background levels, there is almost no safety margin for the effects of ambient O(3) on airway permeability. The assay of CC16 in the serum represents a new sensitive noninvasive test allowing the detection of early effects of ambient O(3) on the lung epithelial barrier. Images Figure 1 Figure 2 Figure 3 PMID:10856027

  3. Serum level of miR-10-5p as a prognostic biomarker for acute myeloid leukemia.

    PubMed

    Zhi, Yongjin; Xie, Xiaobao; Wang, Rong; Wang, Biao; Gu, Weiying; Ling, Yun; Dong, Weimin; Zhi, Feng; Liu, Yan

    2015-09-01

    MicroRNAs (miRNAs) are a type of small non-coding RNA molecule that play important roles in tumor initiation, chemotherapy response, promotion, and progression by negatively interfering with gene expression. The aim of the present study was to investigate the serum expression status and explore the prognostic significance of miR-10a-5p in acute myeloid leukemia (AML). The serum expression level of miR-10a-5p in de novo AML was significantly higher, compared with that in controls. The area under the receiver operator characteristic (ROC) curve was of 0.831 in the diagnostic value of miR-10a-5p. In the complete remission (CR) group, the serum expression level of miR-10a-5p was similar to that of healthy subjects and demonstrated a significant downtrend when compared to that on the day of diagnosis. Nevertheless, miR-10a-5p expression was found to significantly increase in cases of relapsed AML when compared individually to the CR population. On analysis of the association of miR-10a-5p expression with the clinical characteristics at diagnosis in AML patients, lower CR rates occurred more frequently in the high-expression group. In addition, high miR-10a-5p expression was associated with poorer overall survival (OS). These data suggest that miR-10a-5p may serve as a biomarker useful to improving the management of AML patients. PMID:26134365

  4. Effects of smoking and smoking cessation on human serum metabolite profile: results from the KORA cohort study

    PubMed Central

    2013-01-01

    Background Metabolomics helps to identify links between environmental exposures and intermediate biomarkers of disturbed pathways. We previously reported variations in phosphatidylcholines in male smokers compared with non-smokers in a cross-sectional pilot study with a small sample size, but knowledge of the reversibility of smoking effects on metabolite profiles is limited. Here, we extend our metabolomics study with a large prospective study including female smokers and quitters. Methods Using targeted metabolomics approach, we quantified 140 metabolite concentrations for 1,241 fasting serum samples in the population-based Cooperative Health Research in the Region of Augsburg (KORA) human cohort at two time points: baseline survey conducted between 1999 and 2001 and follow-up after seven years. Metabolite profiles were compared among groups of current smokers, former smokers and never smokers, and were further assessed for their reversibility after smoking cessation. Changes in metabolite concentrations from baseline to the follow-up were investigated in a longitudinal analysis comparing current smokers, never smokers and smoking quitters, who were current smokers at baseline but former smokers by the time of follow-up. In addition, we constructed protein-metabolite networks with smoking-related genes and metabolites. Results We identified 21 smoking-related metabolites in the baseline investigation (18 in men and six in women, with three overlaps) enriched in amino acid and lipid pathways, which were significantly different between current smokers and never smokers. Moreover, 19 out of the 21 metabolites were found to be reversible in former smokers. In the follow-up study, 13 reversible metabolites in men were measured, of which 10 were confirmed to be reversible in male quitters. Protein-metabolite networks are proposed to explain the consistent reversibility of smoking effects on metabolites. Conclusions We showed that smoking-related changes in human serum

  5. Proteomic analysis of serum proteins in triple transgenic Alzheimer's disease mice: implications for identifying biomarkers for use to screen potential candidate therapeutic drugs for early Alzheimer's disease.

    PubMed

    Sui, Xiaojing; Ren, Xiaohu; Huang, Peiwu; Li, Shuiming; Ma, Quan; Ying, Ming; Ni, Jiazuan; Liu, Jianjun; Yang, Xifei

    2014-01-01

    Alzheimer's disease (AD) is the most common fatal neurodegenerative disease affecting the elderly worldwide. There is an urgent need to identify novel biomarkers of early AD. This study aims to search for potential early protein biomarkers in serum from a triple transgenic (PS1M146V/APPSwe/TauP301L) mouse model. Proteomic analysis via two-dimensional fluorescence difference gel electrophoresis was performed on serum samples from wild-type (WT) and triple transgenic mice that were treated with or without coenzyme Q10 (CoQ10) (800 mg/kg body weight/day), a powerful endogenous antioxidant displaying therapeutic benefits against AD pathology and cognitive impairment in multiple AD mouse models, for a period of three months beginning at two months of age. A total of 15 differentially expressed serum proteins were identified between the WT and AD transgenic mice. The administration of CoQ10 was found to alter the changes in the differentially expressed serum proteins by upregulating 10 proteins and down-regulating 10 proteins. Among the proteins modulated by CoQ10, clusterin and α-2-macroglobulin were validated via ELISA assay. These findings revealed significant changes in serum proteins in the AD mouse model at an early pathological stage and demonstrated that administration of CoQ10 could modulate these changes in serum proteins. Our study suggested that these differentially expressed serum proteins could serve as potential protein biomarkers of early AD and that screening for potential candidate AD therapeutic drugs and monitoring of therapeutic effects could be performed via measurement of the changes in these differentially expressed serum proteins. PMID:24496070

  6. A Novel Urinary Biomarker Profile to Identify Acute Kidney Injury (AKI) in Critically Ill Neonates - A Pilot Study

    PubMed Central

    Hoffman, Suma Bhat; Massaro, An N.; Soler-García, Ángel A.; Perazzo, Sofia; Ray, Patricio E.

    2014-01-01

    Background The goal of this study was to assess the value of a urinary biomarker profile comprised of Neutrophil Gelatinase-associated Lipocalin (NGAL), Fibroblast Growth Factor-2 (FGF-2), and Epidermal Growth Factor (EGF), to detect acute kidney injury (AKI) in critically ill neonates. Methods We conducted a prospective cohort pilot study of at-risk neonates treated in a level IIIC neonatal intensive care unit (NICU) with therapeutic hypothermia (HT) (n = 25) or extracorporeal membrane oxygenation (ECMO) (n=10). Urine was collected at baseline, 48 hours of illness, and > 24 hours post recovery of their corresponding treatments. Control samples were collected from 27 healthy newborns. The data were expressed as urinary concentrations and values normalized for urinary creatinine. AKI was defined as the presence of oliguria >24 hours and/or elevated serum creatinine (SCr), or the failure to improve the estimated creatinine clearance (eCCL) by >50% post recovery. Non-parametric statistical tests and ROC analyses were used to interpret the data. Results Fifteen at risk newborns had AKI. In the first 48 hours of illness, the urinary levels of NGAL and FGF-2 had high sensitivity but poor specificity to identify neonates with AKI. At recovery, low urinary EGF levels identified neonates with AKI with a sensitivity of 74% and specificity of 84%. Overall, in the early stages of a critical illness, the urinary levels of NGAL and FGF-2 were sensitive, but not specific, to identify neonates at risk of AKI. Low EGF levels post-recovery, identified critically ill neonates with AKI. Conclusions These findings require validation in larger prospective studies. PMID:23783654

  7. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

    PubMed Central

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-01-01

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

  8. Serum metabolite profiles of postoperative fatigue syndrome in rat following partial hepatectomy

    PubMed Central

    Lu, Ye; Yang, Rui; Jiang, Xin; Yang, Yajuan; Peng, Fei; Yuan, Hongbin

    2016-01-01

    Postoperative fatigue syndrome is a general complication after surgery. However, there is no ‘‘gold standard’’ for fatigue assessment due to the lack of objective biomarkers. In this study, a rodent model of postoperative fatigue syndrome based on partial hepatectomy was firstly established and serum metabonomic method based on ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied. Partial least-squares discriminant analysis was used to identify the differential metabolites in 70% partial hepatectomy rats relative to sham rats and 30% partial hepatectomy rats, which showed 70% partial hepatectomy group was significantly distinguishable from 30% partial hepatectomy group and sham group. Eighteen serum metabolites responsible for the discrimination were identified. The levels of hypoxanthine, kynurenine, tryptophan, uric acid, phenylalanine, palmitic acid, arachidonic acid and oleic acid showed progressive elevation from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group, and levels of valine, tyrosine, isoleucine, linoleyl carnitine, palmitoylcarnitine, lysophosphatidylcholine (16:0), lysophosphatidylcholine (20:3), citric acid, succinic acid and hippuric acid showed progressive declining trend from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group. These potential biomarkers help to understand of etiology, pathophysiology and treatment of postoperative fatigue syndrome. PMID:27257346

  9. Serum metabolite profiles of postoperative fatigue syndrome in rat following partial hepatectomy.

    PubMed

    Lu, Ye; Yang, Rui; Jiang, Xin; Yang, Yajuan; Peng, Fei; Yuan, Hongbin

    2016-05-01

    Postoperative fatigue syndrome is a general complication after surgery. However, there is no ''gold standard'' for fatigue assessment due to the lack of objective biomarkers. In this study, a rodent model of postoperative fatigue syndrome based on partial hepatectomy was firstly established and serum metabonomic method based on ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied. Partial least-squares discriminant analysis was used to identify the differential metabolites in 70% partial hepatectomy rats relative to sham rats and 30% partial hepatectomy rats, which showed 70% partial hepatectomy group was significantly distinguishable from 30% partial hepatectomy group and sham group. Eighteen serum metabolites responsible for the discrimination were identified. The levels of hypoxanthine, kynurenine, tryptophan, uric acid, phenylalanine, palmitic acid, arachidonic acid and oleic acid showed progressive elevation from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group, and levels of valine, tyrosine, isoleucine, linoleyl carnitine, palmitoylcarnitine, lysophosphatidylcholine (16:0), lysophosphatidylcholine (20:3), citric acid, succinic acid and hippuric acid showed progressive declining trend from sham group to 30% partial hepatectomy group to 70% partial hepatectomy group. These potential biomarkers help to understand of etiology, pathophysiology and treatment of postoperative fatigue syndrome. PMID:27257346

  10. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review.

    PubMed

    Zhao, Xue; Gang, Xiaokun; Liu, Yujia; Sun, Chenglin; Han, Qing; Wang, Guixia

    2016-01-01

    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. PMID:27517054

  11. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review

    PubMed Central

    Sun, Chenglin

    2016-01-01

    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. PMID:27517054

  12. Untargeted metabolic profiling reveals potential biomarkers in myocardial infarction and its application.

    PubMed

    Yao, Hong; Shi, Peiying; Zhang, Ling; Fan, Xiaohui; Shao, Qing; Cheng, Yiyu

    2010-06-01

    Although some important biomarkers for myocardial injury have been identified, there still lacks a systematic view of the development and progression of myocardial infarction, including enzymatic regulation, metabolite levels, fluxes, etc., which are pivotal to elucidate the physiological mechanism of disease. Here we present an untargeted analytical approach based on gas chromatography coupled with mass spectrometry (GC-MS) to map the temporal metabolic profilings in blood sera of myocardial infarction rat model prepared by left coronary artery ligation. Using XCMS software (http://metlin.scripps.edu/download/), data processing was simplified greatly. We identified the changes in circulating levels of 24 metabolites during the myocardial ischemia. By combination of previous proteomic results, it gives rise to a new insight view of energy metabolism changes referring to anaerobic glycolysis, citric acid cycle, fatty acid beta-oxidation, and some amino acids metabolism. With these altered metabolism pathways as possible drug targets, we validated a role for the presented metabonomic profiling in the systematic understanding of the action mechanism of component-complex medicine herbs, such as Radix Ophiopogonis, a widely-used anti-myocardial ischemia herbal medicine in Asia.

  13. Assessing novel prognostic serum biomarkers in advanced pancreatic cancer: the role of CYFRA 21-1, serum amyloid A, haptoglobin, and 25-OH vitamin D3.

    PubMed

    Haas, Michael; Kern, Christoph; Kruger, Stephan; Michl, Marlies; Modest, Dominik P; Giessen, Clemens; Schulz, Christoph; von Einem, Jobst C; Ormanns, Steffen; Laubender, Rüdiger P; Holdenrieder, Stefan; Heinemann, Volker; Boeck, Stefan

    2015-04-01

    The present prospective single-center study investigated the prognostic role of novel serum biomarkers in advanced pancreatic cancer (PC). Patients (pts) with locally advanced or metastatic PC treated with first-line palliative chemotherapy were included. Among others, the serum markers CYFRA 21-1, haptoglobin, serum-amyloid A (SAA), and 25-OH vitamin D3 were determined at baseline and categorized by pre-defined cut-offs [median values (MV), upper limits of normal (ULN), lower limits of normal (LLN), or the natural logarithm (ln)] and correlated with overall survival (OS). Among the 59 pts included, pre-treatment CYFRA 21-1 levels showed a strong correlation with OS independent of the applied cut-off (MV 4.9 ng/ml-14.2 vs. 4.2 months, HR 0.18, p = 0.001; ULN 3.3 ng/ml-14.2 vs. 4.4 months, HR 0.28, p = 0.003; [ln] CYFRA 21-1-HR 0.77, p = 0.013). Lower values of haptoglobin were additionally associated with an improvement in OS (categorized by LLN of 2.05 g/l-10.4 vs. 5.5 months, HR 0.46, p = 0.023; [ln] haptoglobin-HR 0.51, p = 0.036). Pts with baseline SAA values below the MV of 22 mg/l also had a prolonged OS (10.4 vs. 5.0 months, HR 0.47, p = 0.036). For 25-OH vitamin D3 levels, no significant correlation with OS was found. In multivariate analyses, pre-treatment CYFRA 21-1 levels (categorized by MV-HR 0.15, p = 0.032) as well as [ln] haptoglobin (HR 0.30, p = 0.006) retained their independent prognostic significance for OS. CYFRA 21-1, haptoglobin, and SAA might provide useful prognostic information in advanced PC. An external multicenter validation of these results is necessary. PMID:25472579

  14. Tea Dietary Fiber Improves Serum and Hepatic Lipid Profiles in Mice Fed a High Cholesterol Diet.

    PubMed

    Guo, Wenxin; Shu, Yang; Yang, Xiaoping

    2016-06-01

    Tea dietary fiber (TDF) was prepared from tea residues and modified to get cellulose-modified TDF (CTDF) by cellulase or micronized TDF (MTDF) by ultrafine grinding. The in vitro lipid-binding capacities of the three fibers and their effects on serum and hepatic lipid profiles in mice fed a high cholesterol diet were evaluated. The results showed that the three fibers had excellent lipid-binding capacities, and the cholesterol- and sodium cholate-binding capacities of CTDF and MTDF were significantly higher than those of TDF. Animal studies showed that, compared to model control, the three fibers significantly decreased mice average daily gain, gain: feed, and liver index, reduced total cholesterol (TC), triglyceride, and low density lipoprotein-cholesterol of serum and liver, increased serum and hepatic high density lipoprotein-cholesterol to TC ratio, and promoted the excretion of fecal lipids, and they also significantly increased the activities of superoxide dismutase and glutathione peroxidase of serum and liver, and decreased lipid peroxidation; moreover, the effects of CTDF and MTDF were better than that of TDF. It was concluded that the three fibers could improve serum and hepatic lipid profiles in mice fed a high cholesterol diet and the mechanism of action might be due to the promotion of fecal excretion of lipids through their lipid-binding ability and the inhibition of lipid peroxidation. These findings suggest that tea dietary fiber has the potential to be used as a functional ingredient to control cardiovascular disease.

  15. Putative Role of Serum Amyloid-A and Proinflammatory Cytokines as Biomarkers for Behcet's Disease

    PubMed Central

    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

  16. A Systematic Review and Meta-Analysis of Diagnostic and Prognostic Serum Biomarkers of Colorectal Cancer

    PubMed Central

    Liu, Zhongyu; Zhang, Yingchong; Niu, Yulong; Li, Ke; Liu, Xin; Chen, Huijuan; Gao, Chunfang

    2014-01-01

    Background Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC). Methods 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. Results 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. Conclusions 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. PMID:25105762

  17. Quantification of a Cardiac Biomarker in Human Serum Using Extraordinary Optical Transmission (EOT)

    PubMed Central

    Ding, Tao; Hong, Minghui; Richards, A. Mark; Wong, Ten It; Zhou, Xiaodong; Drum, Chester Lee

    2015-01-01

    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. PMID:25774658

  18. Serum IL-6: a candidate biomarker for intracranial pressure elevation following isolated traumatic brain injury

    PubMed Central

    2010-01-01

    Background Increased intracranial pressure (ICP) is a serious, life-threatening, secondary event following traumatic brain injury (TBI). In many cases, ICP rises in a delayed fashion, reaching a maximal level 48-96 hours after the initial insult. While pressure catheters can be implanted to monitor ICP, there is no clinically proven method for determining a patient's risk for developing this pathology. Methods In the present study, we employed antibody array and Luminex-based screening methods to interrogate the levels of inflammatory cytokines in the serum of healthy volunteers and in severe TBI patients (GCS≤8) with or without incidence of elevated intracranial pressure (ICP). De-identified samples and ELISAs were used to confirm the sensitivity and specificity of IL-6 as a prognostic marker of elevated ICP in both isolated TBI patients, and polytrauma patients with TBI. Results Consistent with previous reports, we observed sustained increases in IL-6 levels in TBI patients irrespective of their ICP status. However, the group of patients who subsequently experienced ICP ≥ 25 mm Hg had significantly higher IL-6 levels within the first 17 hours of injury as compared to the patients whose ICP remained ≤20 mm Hg. When blinded samples (n = 22) were assessed, a serum IL-6 cut-off of <5 pg/ml correctly identified 100% of all the healthy volunteers, a cut-off of >128 pg/ml correctly identified 85% of isolated TBI patients who subsequently developed elevated ICP, and values between these cut-off values correctly identified 75% of all patients whose ICP remained ≤20 mm Hg throughout the study period. In contrast, the marker had no prognostic value in predicting elevated ICP in polytrauma patients with TBI. When the levels of serum IL-6 were assessed in patients with orthopedic injury (n = 7) in the absence of TBI, a significant increase was found in these patients compared to healthy volunteers, albeit lower than that observed in TBI patients. Conclusions Our

  19. Metabolic profiling reveals biochemical pathways and potential biomarkers associated with the pathogenesis of Krabbe disease.

    PubMed

    Weinstock, Nadav I; Wrabetz, Lawrence; Feltri, M Laura; Shin, Daesung

    2016-11-01

    Krabbe disease (KD) is caused by mutations in the galactosylceramidase (GALC) gene, which encodes a lysosomal enzyme that degrades galactolipids, including galactosylceramide and galactosylsphingosine (psychosine). GALC deficiency results in progressive intracellular accumulation of psychosine, which is believed to be the main cause for the demyelinating neurodegeneration in KD pathology. Umbilical cord blood transplantation slows disease progression when performed presymptomatically but carries a significant risk of morbidity and mortality. Accurate presymptomatic diagnosis is therefore critical to facilitate the efficacy of existing transplant approaches and to avoid unnecessary treatment of children who will not develop KD. Unfortunately, current diagnostic criteria, including GALC activity, genetic analysis, and psychosine measurement, are insufficient for secure presymptomatic diagnosis. This study performs a global metabolomic analysis to identify pathogenetic metabolic pathways and novel biomarkers implicated in the authentic mouse model of KD known as twitcher. At a time point before onset of signs of disease, twitcher hindbrains had metabolic profiles similar to WT, with the exception of a decrease in metabolites related to glucose energy metabolism. Many metabolic pathways were altered after early signs of disease in the twitcher, including decreased phospholipid turnover, restricted mitochondrial metabolism of branched-chain amino acids, increased inflammation, and changes in neurotransmitter metabolism and osmolytes. Hypoxanthine, a purine derivative, is increased before signs of disease appear, suggesting its potential as a biomarker for early diagnosis of KD. Additionally, given the early changes in glucose metabolism in the pathogenesis of KD, diagnostic modalities that report metabolic function, such as positron emission tomography, may be useful in KD. © 2016 Wiley Periodicals, Inc. PMID:27638595

  20. miRNA profiling of circulating EpCAM(+) extracellular vesicles: promising biomarkers of colorectal cancer.

    PubMed

    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. PMID:27576678

  1. miRNA profiling of circulating EpCAM+ extracellular vesicles: promising biomarkers of colorectal cancer

    PubMed Central

    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. PMID:27576678

  2. Acute Phase Response, Inflammation and Metabolic Syndrome Biomarkers of Libby Asbestos Exposure

    EPA Science Inventory

    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 ...

  3. On-chip immunoassay of a cardiac biomarker in serum using a polyester-toner microchip.

    PubMed

    Kim, Ah Rahn; Kim, Joo Yeon; Choi, Kihwan; Chung, Doo Soo

    2013-05-15

    An on-chip immunoassay to detect C-reactive protein (CRP) was performed using a polyester-toner (PT) microchip. CRP is a highly conserved plasma protein responding to inflammation and is used for clinical purposes to diagnose an inflammatory state. For rapid analysis and specific interactions in immunoassays, extensive studies using microfluidic chips have been carried out. Recently, a simple technique to fabricate a disposable PT microchip by a direct printing process was developed and several applications were introduced. One major drawback of the PT microchip, however, is the poor separation performance due to the quality of the microfluidic structures. This problem for a PT microchip can be overcome using a cleavable tag immunoassay, which requires minimal separation performance. After analytes are conjugated onto antibodies which are immobilized on the surface of microbeads placed on the PT microchip, a second group of fluorescently tagged antibodies are added and complexed with the analytes. The tag is then cleaved and the solution containing the cleaved tag is analyzed by electrophoresis. The time needed for the complete analysis to be carried out on a PT microchip was less than 35 min. The dynamic range of the CRP in 10-fold diluted serum was 0.3-100 mg/L and the limit of detection was 0.3 mg/L, which demonstrated the possibility of a quantitative analysis of CRP in serum in clinical trials.

  4. Proteomic study of serum using gel chromatography and MALDI-TOF MS reveals diagnostic biomarkers in male patients with liver-cancer

    NASA Astrophysics Data System (ADS)

    Zeng, Xin-Hua; Huang, He-Qing; Chen, Dong-Shi; Jin, Hong-Wei; Huang, Hui-Ying

    2007-03-01

    Human serum has been widely employed clinically for diagnosing various fatal diseases. However, the concentration of most proteins in human serum is too low to be directly measured using normal analytical methods. In order to obtain reliable analytical results from proteomic analysis of human serum, appropriate sample preparation is essential. A combined off-line analytical technique of gel chromatography and matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS) has been successfully established to separate proteins for MS analysis. Using these combined techniques, 176 mass signal peaks of proteins/peptides were found in 6 of 18 fractions from normal male serum (NMS) in the presence of buffer consisting of NH4HCO3 and acetonitrile. A simple gel chromatography column packed with Sephadex G-50 removed most signal-suppressing compounds such as salts and high abundance proteins (HAP). The molecular mass to charge (m/z) ratios of differential peptides revealed in serum of male patient with liver-cancer (LCMPS) compared to NMS were 5365, 5644 and 6462, and these peptides can be used as biomarkers to clinically diagnose liver-cancer. The simple and convenient chromatographic method described here is not only superior to recently described HPLC separation for MS analysis, but also reveals many novel and significant serum biomarkers for the clinical diagnosis of various diseases.

  5. Changes in serum lipid profile in the acute and convalescent Plasmodium vivax malaria: A cohort study.

    PubMed

    Mesquita, Teresinha C; Martin, Thamires G O; Alves, Eduardo R; Mello, Marcia B C; Nery, Andreia F; Gomes, Luciano T; Fontes, Cor Jesus F

    2016-11-01

    Although serum lipids are known to be altered in Plasmodium falciparum-induced malaria, little is known about such changes due to Plasmodium vivax infection. This cohort study assessed serum concentrations of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 164 patients in the acute phase of malaria caused by P. vivax and characterized these changes in the convalescent phase after treatment with chloroquine and primaquine. Compared to reference values, serum total cholesterol, LDL, and HDL levels were lower and triglyceride levels were higher in the acute phase. Moreover, the parasite density was negatively correlated with LDL (r=-0,189; p=0.027) and HDL (r=-0,256; p=0.001) serum levels. Eighty patients returned for clinical and laboratory revaluation 7-12days after treatment initiation. All patients showed parasite clearance and the absence of symptoms during the convalescent phase. Analysis of the serum lipids of these 80 patients showed significant increases in the serum levels of total cholesterol (p<0.0001), LDL (p<0.0001), and HDL (p<0.0001) as well as a significant reduction in triglycerides (p=0.004), indicating a trend towards a return to normal levels. This transient change in lipid profile between the acute and convalescent stages may be useful for the clinical monitoring of patients treated for vivax malaria. PMID:27461878

  6. Changes in serum lipid profile in the acute and convalescent Plasmodium vivax malaria: A cohort study.

    PubMed

    Mesquita, Teresinha C; Martin, Thamires G O; Alves, Eduardo R; Mello, Marcia B C; Nery, Andreia F; Gomes, Luciano T; Fontes, Cor Jesus F

    2016-11-01

    Although serum lipids are known to be altered in Plasmodium falciparum-induced malaria, little is known about such changes due to Plasmodium vivax infection. This cohort study assessed serum concentrations of triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) in 164 patients in the acute phase of malaria caused by P. vivax and characterized these changes in the convalescent phase after treatment with chloroquine and primaquine. Compared to reference values, serum total cholesterol, LDL, and HDL levels were lower and triglyceride levels were higher in the acute phase. Moreover, the parasite density was negatively correlated with LDL (r=-0,189; p=0.027) and HDL (r=-0,256; p=0.001) serum levels. Eighty patients returned for clinical and laboratory revaluation 7-12days after treatment initiation. All patients showed parasite clearance and the absence of symptoms during the convalescent phase. Analysis of the serum lipids of these 80 patients showed significant increases in the serum levels of total cholesterol (p<0.0001), LDL (p<0.0001), and HDL (p<0.0001) as well as a significant reduction in triglycerides (p=0.004), indicating a trend towards a return to normal levels. This transient change in lipid profile between the acute and convalescent stages may be useful for the clinical monitoring of patients treated for vivax malaria.

  7. Proteomic Analysis of Human Serum for Finding Pathogenic Factors and Potential Biomarkers in Preeclampsia

    PubMed Central

    Liu, Chongdong; Zhang, Nawei; Yu, Haiqiang; Chen, Yuxuan; Liang, Yong; Deng, Haiteng; Zhang, Zhenyu

    2010-01-01

    Objective(s) To apply a novel proteomic method to discover potential pathogenic factors and biomarkers of preeclampsia. Study design Sera from five patients complicated with preeclampsia and five healthy pregnant controls were separately pooled. Each pool was treated with peptide ligand library beads (PLLBs) to remove high abundance proteins by affinity and thus enrich low abundance proteins. The proteins from the eluate were analyzed by a combination of 1D-Gel-LC-MS/MS. Protein expression levels were quantified using spectral counts and the extracted ion current. Results 1172 unique proteins in preeclampsia and 1149 in healthy controls were identified in the present study. 51 proteins were differentially expressed between preeclampsia and healthy pregnant women including chorionic somatommammptropin hormone (CSH) and fibulin-1. 31 proteins identified were up-regulated and 20 were down-regulated. Conclusions The results demonstrate that peptide ligand library combining with 1D gel-LC-MS/MS analysis is an efficient method to identify differentially expressed proteins in sera and two biological processes of complement and coagulation activations and lipid metabolism were involved in the pathogenesis of preeclampsia. PMID:21145106

  8. Two of Them Do It Better: Novel Serum Biomarkers Improve Autoimmune Hepatitis Diagnosis

    PubMed Central

    Cardaci, Angela; Rossi, Riccardo Lorenzo; Muratori, Luigi; Abrignani, Sergio; Bombaci, Mauro

    2015-01-01

    Background Autoimmune hepatitis (AIH) is a chronic liver disease of unknown aetiology and characterized by continuing hepatocellular inflammation and necrosis. Autoantibodies represent accessible markers to measure the adaptive immune responses in the clinical investigation. Protein microarrays have become an important tool to discriminate the disease state from control groups, even though there is no agreed-upon standard to analyze the results. Results In the present study 15 sera of patients with AIH and 78 healthy donors (HD) have been tested against 1626 proteins by an in house-developed array. Using a Partial Least Squares Discriminant Analysis (PLS-DA) the resulting data interpretation led to the identification of both new and previously identified proteins. Two new proteins AHPA9419 and Chondroadherin precursor (UNQ9419 and CHAD, respectively), and previously identified candidates as well, have been confirmed in a validation phase by DELFIA assay using a new cohort of AIH patients. A receiver operating characteristic analysis was used for the evaluation of biomarker candidates. The sensitivity of each autoantigen in AIH ranged from 65 to 88%; moreover, when the combination of the two new autoantigens was analyzed, the sensitivity increased to 95%. Conclusions Our findings demonstrate that the detection of autoantibodies against the two autoantigens could improve the performance in discriminating AIH patients from control classes and in combination with previously identified autoantigens and they could be used in diagnostic/prognostic markers. PMID:26375394

  9. The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression

    PubMed Central

    Ghahremanfard, Farahnaz; Mirmohammadkhani, Majid; Shahnazari, Banafsheh; Gholami, Golnaz; Mehdizadeh, Jamileh

    2015-01-01

    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. PMID:26421116

  10. Promising toxicological biomarkers for the diagnosis of liver injury types: Bile acid metabolic profiles and oxidative stress marker as screening tools in drug development.

    PubMed

    Masubuchi, Noriko; Nishiya, Takayoshi; Imaoka, Masako; Mizumaki, Kiyoko; Okazaki, Osamu

    2016-08-01

    Promising biomarkers were identified in adult male Crl:CD (SD) rats for the screening of new chemical entities for their potential to cause liver injury. We examined the serum biochemistry, liver histopathology, and bile acid profiles by LC-MS/MS, and the mRNA expression of transporters and CYPs by an RT-PCR after the following treatments to male Crl:CD (SD) rats: (a) bile duct ligation (BDL); (b) a single oral dose of 150 mg/kg α-naphthylisothiocyanate (ANIT); and (c) repeated oral doses of a novel pyrrolidinecarboxylic acid derivative (abbreviated as PCA) at 30, 300, and 1000 mg/kg. The serum total bile acid levels and bilirubin concentrations were found to be elevated in all of the groups. However, the bile acid component profiles of the PCA group differed significantly from BDL and ANIT models: deoxycholic acid, lithocholic acid, and sulfated bile acids were upregulated in a dose-dependent manner only in the PCA group. In addition, the PCA group demonstrated high levels of hepatic heme oxygenase-1 expression, whereas the profiles of the mRNA levels of the hepatic transporters and CYPs of all groups were found to be similar. The histopathological findings, for both the BDL and ANIT groups, were of bile duct hyperplasia, hepatocyte degeneration and necrosis. In contrast, only bile duct hyperplasia and hepatocyte degeneration were observed in the PCA group, even at a lethal dose. These results indicated that PCA induced a cholestatic condition and the increase of oxidative stress markers implies that this will also lead hepatocellular injury. In conclusion, the serum bile acid components and sulfated bile acid levels, and the expression of oxidative stress markers could provide information that aids in the diagnosis of liver injury type and helps to elucidate the mechanisms of hepatotoxicity. These findings can be extrapolated into our clinical investigation. The analysis of these crucial biomarkers is likely to be a useful screening tool in the lead

  11. A Model for Mild Traumatic Brain Injury that Induces Limited Transient Memory Impairment and Increased Levels of Axon Related Serum Biomarkers

    PubMed Central

    Rostami, Elham; Davidsson, Johan; Ng, Kian Chye; Lu, Jia; Gyorgy, Andrea; Walker, John; Wingo, Daniel; Plantman, Stefan; Bellander, Bo-Michael; Agoston, Denes V.; Risling, Mårten

    2012-01-01

    Mild traumatic brain injury (mTBI) is one of the most common neuronal insults and can lead to long-term disabilities. mTBI occurs when the head is exposed to a rapid acceleration-deceleration movement triggering axonal injuries. Our limited understanding of the underlying pathological changes makes it difficult to predict the outcome of mTBI. In this study we used a scalable rat model for rotational acceleration TBI, previously characterized for the threshold of axonal pathology. We have analyzed whether a TBI just above the defined threshold would induce any detectable behavioral changes and/or changes in serum biomarkers. The effect of injury on sensory motor functions, memory and anxiety were assessed by beam walking, radial arms maze and elevated plus maze at 3–7 days following TBI. The only behavioral deficits found were transient impairments in working and reference memory. Blood serum was analyzed at 1, 3, and 14 days after injury for changes in selected protein biomarkers. Serum levels of neurofilament heavy chain and Tau, as well as S100B and myelin basic protein showed significant increases in the injured animals at all time points. No signs of macroscopic injuries such as intracerebral hematomas or contusions were found. Amyloid precursor protein immunostaining indicated axonal injuries at all time points analyzed. In summary, this model mimics some of the key symptoms of mTBI, such as transient memory impairment, which is paralleled by an increase in serum biomarkers. Our findings suggest that serum biomarkers may be used to detect mTBI. The model provides a suitable foundation for further investigation of the underlying pathology of mTBI. PMID:22837752

  12. Serum Biomarkers Associated with Clinical Outcomes Fail to Predict Brain Metastases in Patients with Stage IV Non-Small Cell Lung Cancers

    PubMed Central

    Li, Bob T.; Lou, Emil; Hsu, Meier; Yu, Helena A.; Naidoo, Jarushka; Zauderer, Marjorie G.; Sima, Camelia; Johnson, Melissa L.; Daras, Mariza; DeAngelis, Lisa M.; Fleisher, Martin; Kris, Mark G.; Azzoli, Christopher G.

    2016-01-01

    Background Lung cancers account for the majority of brain metastases which pose major therapeutic challenges. Biomarkers prognosticating for the development of brain metastases in patients with non-small cell lung cancers (NSCLC) may improve personalized care. Six serum proteomic biomarkers were previously investigated at Memorial Sloan Kettering but their associations with brain metastases were unknown. Methods Serum NSE, CYFRA 21–1, ProGRP, SCC-Ag, TIMP1, and HE4 by ELISA-based proteomic assays were prospectively collected from consecutive patients with stage IV NSCLC. Pre-treatment serum biomarker levels as well as age, histology, and epidermal growth factor receptor (EGFR) mutation status were evaluated for association with the baseline presence of brain metastases using logistic regression and multivariable analysis. For patients without brain metastases at baseline, the cumulative incidence of subsequent brain metastases were compared according to baseline biomarkers and clinical factors using Gray’s test. Results A total of 118 patients were enrolled, 31 (26%; 95% CI 0.19–0.35) had brain metastases at baseline and a further 26 (22%; 95% CI 0.15–0.30) developed brain metastases subsequently. Pre-treatment serum biomarker levels were available in 104 patients. There was no significant association between the six serum biomarkers and the baseline presence or subsequent development of brain metastases. Age younger than 65 years was the only clinical factor significantly associated with brain metastasis at baseline (OR 3.00; 95% CI 1.22–7.34, P = 0.02) by multivariable analysis. A trend toward increased cumulative incidence of subsequent brain metastases was observed in patients with EGFR mutation (p = 0.2), but this was not statistically significant possibly due to small sample size. Conclusions Serum NSE, CYFRA 21–1, Pro-GRP, SCC-Ag, TIMP1, and HE4 are not significantly associated with brain metastases. Our methods taking into account follow-up time

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

    SciTech Connect

    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.

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

    SciTech Connect

    Vogelzang, Nicolas; Fink, Louis

    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 speciment 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 biiomarkers for staging different cancers and to detect patient responsiveness to therapy at an early state in the treatment process.

  15. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    PubMed

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. PMID:27357802

  16. White blood cell count in women: relation to inflammatory biomarkers, haematological profiles, visceral adiposity, and other cardiovascular risk factors.

    PubMed

    Farhangi, Mahdieh Abbasalizad; Keshavarz, Seyyed-Ali; Eshraghian, Mohammadreza; Ostadrahimi, Alireza; Saboor-Yaraghi, Ali-Akbar

    2013-03-01

    The role of white blood cell (WBC) count in pathogenesis of diabetes, cardiovascular disease, and obesity-related disorders has been reported earlier. Recent studies revealed that higher WBC contributes to atherosclerotic progression and impaired fasting glucose. However, it is unknown whether variations in WBC and haematologic profiles can occur in healthy obese individuals. The aim of this study is to further evaluate the influence of obesity on WBC count, inflammatory biomarkers, and metabolic risk factors in healthy women to establish a relationship among variables analyzed. The sample of the present study consisted of 84 healthy women with mean age of 35.56 +/- 6.83 years. They were categorized into two groups based on their body mass index (BMI): obese group with BMI > 30 kg/m2 and non-obese group with BMI < 30 kg/m2. We evaluated the relationship between WBC and platelet count (PLT) with serum interleukin 6 (IL-6), C-reactive protein (CRP), angiotensin pi (Ang pi), body fat percentage (BF %), waist-circumference (WC), and lipid profile. WBC, PLT, CRP, and IL-6 in obese subjects were significantly higher than in non-obese subjects (p < 0.05). The mean WBC count in obese subjects was 6.4 +/- 0.3 (x10(9)/L) compared to 4.4 +/- 0.3 (x10(9)/L) in non-obese subjects (p = 0.035). WBC correlated with BF% (r = 0.31, p = 0.004), CRP (r = 0.25, P = 0.03), WC (r = 0.22, p = 0.04), angiotensin 11 (r = 0.24, p = 0.03), triglyceride (r = 0.24, p = 0.03), and atherogenic index of plasma (AIP) levels (r = 0.3, p = 0.028) but not with IL-6. Platelet count was also associated with WC and waist-to-hip ratio (p < 0.05). Haemoglobin and haematocrit were in consistent relationship with LDL-cholesterol (p < 0.05). In conclusion, obesity was associated with higher WBC count and inflammatory parameters. There was also a positive relationship between WBC count and several inflammatory and metabolic risk factors in healthy women.

  17. Validation of Serum Biomarkers Derived from Proteomic Analysis for the Early Screening of Preeclampsia

    PubMed Central

    Kolialexi, Aggeliki; Gourgiotis, Dimitrios; Daskalakis, George; Marmarinos, Antonis; Lykoudi, Alexandra; Mavreli, Danai; Mavrou, Ariadni; Papantoniou, Nikolas

    2015-01-01

    Aim. To examine the potential value of previously identified biomarkers using proteomics in early screening for preeclampsia (PE). Methods. 24 blood samples from women who subsequently developed PE and 48 from uncomplicated pregnancies were obtained at 11–13 weeks and analysed after delivery. Cystatin-C, sVCAM-1, and Pappalysin-1 were quantified by ELISA. Maternal characteristics and medical history were recorded. Results. Median values of Cystatin-C, sVCAM-1, and Pappalysin-1 in the PE group as compared to controls were 909.1 gEq/mL versus 480.0 gEq/mL, P = .000, 832.0 gEq/mL versus 738.8 gEq/mL, P = .024, and 234.4 gEq/mL versus 74.9 gEq/mL, P = .064, respectively. Areas under the receiver-operating characteristic curves (AUC, standard error (SE)) for predicting PE were Cystatin-C: 0.90 (SE 0.04), VCAM-1: 0.66 (SE 0.074), and Pappalysin-1: 0.63 (SE 0.083). To discriminate between cases at risk for PE and normal controls, cut-off values of 546.8 gEq/mL for Cystatin-C, 1059.5 gEq/mL for sVCAM-1, and 220.8 gEq/mL for Pappalysin-1 were chosen, providing sensitivity of 91%, 41%, and 54% and specificity of 85%, 100%, and 95%, respectively. Conclusions. sVCAM-1 and Pappalysin-1 do not improve early screening for PE. Cystatin-C, however, seems to be associated with subsequent PE development, but larger studies are necessary to validate these findings. PMID:25628472

  18. Serum Perfluorooctanoate (PFOA) and Perfluorooctane Sulfonate (PFOS) Concentrations and Liver Function Biomarkers in a Population with Elevated PFOA Exposure

    PubMed Central

    Gallo, Valentina; Leonardi, Giovanni; Genser, Bernd; Lopez-Espinosa, Maria-Jose; Frisbee, Stephanie J.; Karlsson, Lee; Ducatman, Alan M.

    2012-01-01

    Background: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) persist in the environment and are found in relatively high concentrations in animal livers. Studies in humans have reported inconsistent associations between PFOA and liver enzymes. Objectives: We examined the cross-sectional association between serum PFOA and PFOS concentrations with markers of liver function in adults. Methods: The C8 Health Project collected data on 69,030 persons; of these, a total of 47,092 adults were included in the present analysis. Linear regression models were fitted for natural log (ln)-transformed values of alanine transaminase (ALT), γ-glutamyltransferase (GGT), and direct bilirubin on PFOA, PFOS, and potential confounders. Logistic regression models were fitted comparing deciles of PFOA or PFOS in relation to high biomarker levels. A multilevel analysis comparing the evidence for association of PFOA with liver function at the individual level within water districts to that at the population level between water districts was also performed. Results: ln-PFOA and ln-PFOS were associated with ln-ALT in linear regression models [PFOA: coefficient, 0.022; 95% confidence interval (CI): 0.018, 0.025; PFOS: coefficient, 0.020; 95% CI: 0.014, 0.026] and with raised ALT in logistic regression models [with a steady increase in the odds ratio (OR) estimates across deciles of PFOA and PFOS; PFOA: OR = 1.10; 95% CI: 1.07, 1.13; PFOS: OR = 1.13; 95% CI: 1.07, 1.18]. There was less consistent evidence of an association of PFOA and GGT or bilirubin. The relationship with bilirubin appears to rise at low levels of PFOA and to fall again at higher levels. Conclusions: These results show a positive association between PFOA and PFOS concentrations and serum ALT level, a marker of hepatocellular damage. PMID:22289616

  19. A Systemic Inflammatory Endotype of Asthma With More Severe Disease Identified by Unbiased Clustering of the Serum Cytokine Profile

    PubMed Central

    Liang, Zhenyu; Liu, Laiyu; Zhao, Haijin; Xia, Yang; Zhang, Weizhen; Ye, Yanmei; Jiang, Mei; Cai, Shaoxi

    2016-01-01

    Abstract Asthma is considered as a clinical and molecularly heterogeneous disorder. Systemic inflammation is suggested to play an important role in a group of asthma patients. We hypothesized that there is a subgroup of patients with asthma characterized by systemic inflammation. In this study, we aimed to discriminate asthma subtypes based on circulating biomarkers and to determine whether a systemic inflammatory endotype of asthma could be identified. In the present cross-sectional study, 50 patients with untreated asthma were prospectively recruited from a single academic outpatient clinic, and characterized with respect to clinical, functional, and inflammatory parameters. The expression profiles of 20 serum cytokines were assessed by anti-human cytokine antibody array. Then, hierarchical clustering analysis was performed based on principal component analysis (PCA)-transformed data to classify the clinical groups. PCA showed that 6 independent components accounted for 80.113% of the variance, and PCA-based hierarchical clustering identified 3 endotypes. One of the endotypes was evidenced by elevated systemic inflammation markers such as leptin, vascular endothelial growth factor (VEGF), and reduced levels of soluble receptor for advanced glycation end products (sRAGE), an anti-inflammatory molecule. More female patients were included, with higher circulating neutrophil counts and more severe symptoms. In conclusion, we identified an endotype of asthma characterized by systemic inflammation and severe symptoms. Increased levels of VEGF, leptin and decreased level of sRAGE may contribute to the systemic inflammation of this asthma endotype. PMID:27336865

  20. Serum biomarkers combined with uterine artery Doppler in prediction of preeclampsia

    PubMed Central

    Li, Lijie; Zheng, Yanmei; Zhu, Ying; Li, Jianchun

    2016-01-01

    First-trimester screening may be a major advantage over a second-trimester approach since it opens prospects for early and more efficient interventions. The aim of the current study was to evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at three to four months gestation with the second-trimester uterine artery pulsatility index (PI) are useful in predicting preeclampsia in a group of nulliparous women. All the patients also underwent uterine artery Doppler examination to measure the PI at 22–24 weeks gestation. Inhibin A, activin A and PlGF were measured using an ELISA by an examiner who was blinded to the pregnancy outcome. Thirty-eight cases with preeclampsia and 100 controls were analyzed. Second-trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with preeclampsia compared with controls. In pregnancies that developed preeclampsia, the uterine artery PI was increased (1.61±0.047 vs. 1.02±0.049, P<0.001), as was the level of inhibin A (1.72±0.023 vs. 1.03±0.063, P<0.001) and the level of activin A (1.68±0.38 vs. 1.06±0.42, P<0.001) compared with the controls. In contrast, the level of PlGF was decreased in pregnancies that developed preeclampsia compared with the controls (0.69±0.23 vs. 1.00±0.26, P<0.001). A combination of activin A, PlGF and uterine artery PI gave an AUC of 0.915 (95% CI, 0.812–0.928; P<0.001) with a sensitivity of 91% at a specificity of 82%. In our study, we demonstrated that both serum inhibin A and activin A levels were increased, while the PlGF level was decreased in the early second-trimester in women who developed preeclampsia.

  1. Serum biomarkers combined with uterine artery Doppler in prediction of preeclampsia

    PubMed Central

    Li, Lijie; Zheng, Yanmei; Zhu, Ying; Li, Jianchun

    2016-01-01

    First-trimester screening may be a major advantage over a second-trimester approach since it opens prospects for early and more efficient interventions. The aim of the current study was to evaluate whether the measurement of maternal serum inhibin A, activin A and placental growth factor (PlGF) at three to four months gestation with the second-trimester uterine artery pulsatility index (PI) are useful in predicting preeclampsia in a group of nulliparous women. All the patients also underwent uterine artery Doppler examination to measure the PI at 22–24 weeks gestation. Inhibin A, activin A and PlGF were measured using an ELISA by an examiner who was blinded to the pregnancy outcome. Thirty-eight cases with preeclampsia and 100 controls were analyzed. Second-trimester uterine artery PI and marker levels were expressed as multiples of the median (MoM). The uterine artery PI was increased in pregnancies with preeclampsia compared with controls. In pregnancies that developed preeclampsia, the uterine artery PI was increased (1.61±0.047 vs. 1.02±0.049, P<0.001), as was the level of inhibin A (1.72±0.023 vs. 1.03±0.063, P<0.001) and the level of activin A (1.68±0.38 vs. 1.06±0.42, P<0.001) compared with the controls. In contrast, the level of PlGF was decreased in pregnancies that developed preeclampsia compared with the controls (0.69±0.23 vs. 1.00±0.26, P<0.001). A combination of activin A, PlGF and uterine artery PI gave an AUC of 0.915 (95% CI, 0.812–0.928; P<0.001) with a sensitivity of 91% at a specificity of 82%. In our study, we demonstrated that both serum inhibin A and activin A levels were increased, while the PlGF level was decreased in the early second-trimester in women who developed preeclampsia. PMID:27698752

  2. Serum N-Glycan Profiling Predicts Prognosis in Patients Undergoing Hemodialysis

    PubMed Central

    Amano, Maho; Tobisawa, Yuki; Yoneyama, Tohru; Tsushima, Megumi; Hirose, Kazuko; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Saitoh, Hisao; Yamaya, Kanemitsu; Funyu, Tomihisa; Nishimura, Shin-Ichiro; Ohyama, Chikara

    2013-01-01

    Background. The aim of this study is to evaluate the usefulness of serum N-glycan profiling for prognosis in hemodialysis patients. Methods. Serum N-glycan analysis was performed in 100 hemodialysis patients in June 2008 using the glycoblotting method, which allows high-throughput, comprehensive, and quantitative N-glycan analysis. All patients were longitudinally followed up for 5 years. To evaluate the independent predictors for prognosis, patients' background, blood biochemistry, and N-glycans intensity were analyzed using Cox regression multivariate analysis. Selected N-glycans and independent factors were evaluated using the log-rank test with the Kaplan-Meier method to identify the predictive indicators for prognosis. Each patient was categorized according to the number of risk factors to evaluate the predictive potential of the risk criteria for prognosis. Results. In total, 56 N-glycan types were identified in the hemodialysis patients. Cox regression multivariate analysis showed cardiovascular events, body mass index, maximum intima media thickness, and the serum N-glycan intensity of peak number 49 were predictive indicators for overall survival. Risk classification according to the number of independent risk factors revealed significantly poor survival by increasing the number of risk factors. Conclusions. Serum N-glycan profiling may have a potential to predict prognosis in patients undergoing hemodialysis. PMID:24453820

  3. The effect of omega-3 on serum lipid profile in hemodialysis patients

    PubMed Central

    Omrani, Hamid Reza; Pasdar, Yahya; Raisi, Daryosh; Najafi, Farid; Esfandiari, Ardeshir

    2015-01-01

    Introduction: One of the major complications in hemodialysis patients is cardiovascular disease. Lipid abnormality is an important factor in the development of cardiovascular disease. Objectives: To investigate the effect of omega-3 supplementation on serum lipid profile in hemodialysis patients. Patients and Methods: This randomized clinical trial study included 2 groups of patients: those who received omega-3 supplementation (experimental group; 30 cases) and those who received placebo (control group; 30 cases). They received these for 10 weeks and serum lipid profile (triglyceride, high-density lipoprotein [HDL-C], low-density lipoprotein [LDL-C], and total cholesterol) was assessed 2 times, first before initiating supplementation and then at the end of 10-week study period. Results: Mean (±SD) serum total cholesterol levels at the beginning was 163 (±47) mg/dL in experimental group and 143 (±25) mg/dL in control group (P> 0.05). These values decreased to 124 mg/dL and 132 mg/dL in control and experimental groups (P< 0.05). There was no significant difference of HDL-C, LDL-C, or triglyceride levels between experimental and control groups after 10 weeks of treatment. Conclusion: Omega-3 supplementation in hemodialysis patients only showed significant decrease of serum total cholesterol level, but not other lipids. PMID:26468477

  4. Metabolic profile of serum and follicular fluid from postpartum dairy cows during summer and winter.

    PubMed

    Alves, Benner G; Alves, Kele A; Martins, Muller C; Braga, Lucas S; Silva, Thiago H; Alves, Bruna G; Santos, Ricarda M; Silva, Thiago V; Viu, Marco A O; Beletti, Marcello E; Jacomini, José O; Gambarini, Maria L

    2014-01-01

    This study was designed to monitor the biochemical profiles of serum and follicular fluid (FF) of postpartum dairy cows during the summer (n=30) and winter (n=30). Blood and FF (follicles ≥ 9 mm) were obtained from Girolando cows at 30, 45, 60, 75 and 90 days postpartum. The samples were collected and analysed to determine glucose, total cholesterol (TC), triglyceride (TG), urea, sodium (Na), potassium (K) and calcium (Ca) levels. Throughout the study, the following clinical variables were measured: rectal temperature (RT), respiratory rate (RR) and body condition score (BCS). In addition, the temperature humidity index (THI) was calculated for each season. During the summer season, THI was higher, BCS decreased, there was an increase in RT, and glucose, urea, Na and K serum levels were decreased (P<0.05). The levels of TC, TG, urea, K and Ca in follicular fluid increased (P<0.05). Positive correlations (P<0.05) were observed between the serum and FF levels for glucose (r=0.29), TC (r=0.24) and Ca (r=0.30). Therefore, the biochemical profile of serum and FF of dairy cows under summer heat-stress conditions demonstrates marked changes that may impair fertility during lactation.

  5. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    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.

  6. Stem cells, biomarkers and genetic profiling: approaching future challenges in Urology.

    PubMed

    Mancini, Mariangela; Zazzara, Michele; Zattoni, Filiberto

    2016-01-01

    Urological research is facing future challenges, the most difficult one is the fast and meaningful transfer of the massive amount of data from research basic to clinical practice. Between the most important issues that research should focus in the next years are targeting of tumor stem cells, clinical application of biomarkers, and wide application of genetic profiling of urological neoplasms. Several clinical implications are expected, from diagnosis to selection of candidates for different treatment modalities, to modulation of sequential treatment plans, to prognosis. A number of clinical trials based on research data from the hottest issues are in the pipeline. In this review, we will focus on new insights from recent work worlwide in urological research, with particular attention to high-risk nonmuscle-invasive and muscle-invasive bladder cancer, prostate cancer, and kidney cancer. Cancer care is moving towards a personalized approach in patient management. The most important issues in urological research point strongly in this direction and show an enormous potential for the rapid landing of Urology in the era of personalized medicine.

  7. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast

    PubMed Central

    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

    2016-01-01

    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. PMID:26625196

  8. Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis.

    PubMed

    Demirovic, Dino; Rattan, Suresh I S

    2013-01-01

    Aging is the progressive shrinkage of the homeodynamic space. A crucial component of the homeodynamic space is the stress response (SR), by virtue of which a living system senses disturbance and initiates a series of events for maintenance, repair, adaptation, remodeling and survival. Here we discuss the main intracellular SR pathways in human cells, and argue for the need to define and establish the immediate and delayed stress response profiles (SRP) during aging. Such SRP are required to be established at several age-points, which can be the molecular biomarkers of homeodynamic space and the health status of cells and organisms. SRP can also be useful for testing potential protectors and stimulators of homeodynamics, and can be a standard for monitoring the efficacy of potential pro-survival, health-promoting and aging-modulating conditions, food components and other compounds. An effective strategy, which makes use of SRP for achieving healthy aging and extending the healthspan, is that of strengthening the homeodynamics through repeated mild stress-induced hormesis by physical, biological and nutritional hormetins. Furthermore, SRP can also be the basis for defining health as a state of having adequate physical and mental independence of activities of daily living, by identifying a set of measurable parameters at the most fundamental level of biological organization.

  9. Screening of biomarkers in cervical squamous cell carcinomas via gene expression profiling.

    PubMed

    Chen, Bing; Li, Chundong; Zhang, Lei; Lv, Jiahui; Tong, Ying

    2015-11-01

    In the present study, gene expression profiles of high-grade squamous intraepithelial lesions (HSIL) and invasive cervical squamous cell carcinomas (CSCC) were analyzed using bioinformatic tools to identify key genes and potential biomarkers. Analyses of differentially expressed genes (DEGs) were performed for HSIL vs. normal control and invasive CSCC vs. normal control tissues using the Limma package in R. Pathway enrichment analysis was performed using KOBAS. A protein‑protein interaction (PPI) network for the DEGs in invasive CSCC was constructed using String. Functional enrichment analysis was performed for the DEGs in the PPI network using DAVID. Relevant small molecules were predicted using Cmap. A total of 633 and 881 DEGs were identified in HSIL and invasive CSCC, respectively, and the two groups had 305 DEGs in common. Genes associated with the mitogen-activated protein kinase signaling pathway were enriched in the HSIL, while cell cycle-associated genes were over‑represented in invasive CSCC. The PPI network, containing 72 upregulated genes and 434 edges, was illustrated. Functional enrichment analysis showed that the cell cycle was the most significant gene ontology term. A total of six small molecules associated with the pathology of CSCC were identified, including the anti-cancer drug piperlongumine, which showed a negative correlation. The findings of the present study not only enhanced the current understanding of the pathogenesis of CSCC, but may also be a basis for the development of novel therapies. PMID:26398134

  10. Risk factors associated with serum levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor in a general population.

    PubMed

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line Jh; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  11. Metal-linked Immunosorbent Assay (MeLISA): the Enzyme-Free Alternative to ELISA for Biomarker Detection in Serum.

    PubMed

    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. PMID:27446504

  12. Metal-linked Immunosorbent Assay (MeLISA): the Enzyme-Free Alternative to ELISA for Biomarker Detection in Serum

    PubMed Central

    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. PMID:27446504

  13. Risk Factors Associated with Serum Levels of the Inflammatory Biomarker Soluble Urokinase Plasminogen Activator Receptor in a General Population

    PubMed Central

    Haupt, Thomas H; Kallemose, Thomas; Ladelund, Steen; Rasmussen, Line JH; Thorball, Christian W; Andersen, Ove; Pisinger, Charlotta; Eugen-Olsen, Jesper

    2014-01-01

    The soluble urokinase plasminogen activator receptor (suPAR) is a biomarker of mortality risk in various patient populations. However, little is known about the implications of lifestyle for suPAR levels in the general population. Lifestyle, demographic, and cardiovascular disease (CVD) risk factor data were collected from 5,538 participants in the Danish population-based Inter99 study. Their suPAR levels were measured using a sandwich enzyme-linked immunosorbent assay. In the final adjusted model, smoking and morbid obesity were strongly associated with higher suPAR levels (P < 0.001). An unhealthy diet and alcohol abstinence in men were also associated with higher suPAR levels. Physical activity in leisure time had a modest impact on suPAR levels in univariate analysis, but not in the final adjusted model. In conclusion, smoking and morbid obesity were strongly associated with higher serum suPAR levels in this general population. Diet and alcohol consumption also seemed to impact suPAR levels. Lifestyle changes are likely to affect suPAR since ex-smokers had suPAR levels comparable to those of never-smokers. PMID:25574132

  14. Multiplex detection of pathogen biomarkers in human blood, serum, and saliva using silicon photonic microring resonators

    NASA Astrophysics Data System (ADS)

    Estrada, I. A.; Burlingame, R. W.; Wang, A. P.; Chawla, K.; Grove, T.; Wang, J.; Southern, S. O.; Iqbal, M.; Gunn, L. C.; Gleeson, M. A.

    2015-05-01

    Genalyte has developed a multiplex silicon photonic chip diagnostics platform (MaverickTM) for rapid detection of up to 32 biological analytes from a drop of sample in just 10 to 20 minutes. The chips are manufactured with waveguides adjacent to ring resonators, and probed with a continuously variable wavelength laser. A shift in the resonant wavelength as mass binds above the ring resonators is measured and is directly proportional to the amount of bound macromolecules. We present here the ability to multiplex the detection of hemorrhagic fever antigens in whole blood, serum, and saliva in a 16 minute assay. Our proof of concept testing of a multiplex antigencapture chip has the ability to detect Zaire Ebola (ZEBOV) recombinant soluble glycoprotein (rsGP), Marburg virus (MARV) Angola recombinant glycoprotein (rGP) and dengue nonstructural protein I (NS1). In parallel, detection of 2 malaria antigens has proven successful, but has yet to be incorporated into multiplex with the others. Each assay performs with sensitivity ranging from 1.6 ng/ml to 39 ng/ml depending on the antigen detected, and with minimal cross-reactivity.

  15. Serum pattern profiling for analyzing different types of stress by protein chip technology: a preliminary study.

    PubMed

    Liu, Hui; Hou, Diandong; Wu, Da; Yin, Hong; Wu, Xiaoyi

    2010-01-01

    ProteinChip is a widely accepted tool for exploring serum pattern profile to evaluate the risk of somatic diseases from different stressors. In this study, by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-ToF), the serum proteome from mice under restraint and thermal stresses were profiled in detail and compared with the control group. Around 150 characteristic peaks were detected in all three groups, with m/z ranging from 1500 to 50,000, with most peaks being within the 2000 m/z to 20,000 m/z range. Compared with the control group, three significant protein peaks with m/z values of 2780, 3303 and 3450 appeared specifically in the restrained stress group and four other peaks with m/z values of 7500, 7811, 29,950 and 38,565 in the thermal stress group. Unexpectedly, no universal positive stress peaks were detected. These preliminary results clearly suggested that there might not be a common mechanism shared by various psychophysiological disorders under different stressors. By fast serum proteomics profiling, SELDI-ToF may be a convenient tool for evaluating the risk of stress-induced illness.

  16. Effects of a honeybee sting on the serum free amino acid profile in humans.

    PubMed

    Matysiak, Jan; Dereziński, Paweł; Klupczyńska, Agnieszka; Matysiak, Joanna; Kaczmarek, Elżbieta; Kokot, Zenon J

    2014-01-01

    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.

  17. Effects of a Honeybee Sting on the Serum Free Amino Acid Profile in Humans

    PubMed Central

    Matysiak, Jan; Dereziński, Paweł; Klupczyńska, Agnieszka; Matysiak, Joanna; Kaczmarek, Elżbieta; Kokot, Zenon J.

    2014-01-01

    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. PMID:25072247

  18. Effects of a Terrified-Sound Stress on Serum Proteomic Profiling in Mice.

    PubMed

    Yang, Juan; Zhang, Xin; Xiong, Xiaofan; Wu, Qiuhua; Zhao, Lingyu; Liu, Liying; Qin, Yannan; Song, Tusheng; Huang, Chen

    2015-10-01

    The serum proteomic profiles of mice exposed to terrified-sound-induced stress and after stress release were investigated. Serum samples from 32 mice were divided into four groups (n = 8 each) and analyzed using matrix-assisted laser desorption and ionization time-of-flight mass spectrometry techniques (MALDI-TOF MS) combined with magnetic bead-based weak cation-exchange chromatography. ClinProTools software identified several distinct markers that differed between the stressed and control groups and between the stress released and stressed released controls. Of 33 m/z peaks that differed among the four groups, 17 were significantly different (P < 0.05). Five peaks (m/z: 2793.37, 2924.86, 1979.90, 3492.49, 3880.24) showed significant differences in expression after exposure to terrified-sound stress and returned to control levels after stress release. These were sequence identified as peptide regions of dimethylaniline monooxygenase, myosin-9, uncharacterized protein in Rattus norvegicus, apolipoprotein C-I, and plasma serine protease inhibitor (Serpina 5). Our study provides the first evidence of significant changes in serum proteomic profiles in mice exposed to terrified-sound stress, which suggests that protein expression profiles are affected by the stress. Normal expression levels were restored after stress release, suggesting the activation of self-adjustment mechanisms for the recovery of protein expression levels altered by this stress.

  19. miR-22-5p revealed as a potential biomarker involved in the acute phase of myocardial infarction via profiling of circulating microRNAs.

    PubMed

    Maciejak, Agata; Kiliszek, Marek; Opolski, Grzegorz; Segiet, Agnieszka; Matlak, Krzysztof; Dobrzycki, Slawomir; Tulacz, Dorota; Sygitowicz, Grazyna; Burzynska, Beata; Gora, Monika

    2016-09-01

    Acute myocardial infarction (AMI) is a life-threatening episode of coronary artery disease. Recently, circulating myocardial-derived microRNAs (miRNAs) have been reported as potential biomarkers of infarction. The present study aimed to identify differentially expressed miRNAs in patients with ST-segment elevation myocardial infarction that could be potentially dysregulated in response to early myocardial damage. miRNA expression profile analysis was performed using the Serum/Plasma Focus miRNA Polymerase Chain Reaction (PCR) panel of Exiqon A/S (Vedbaek, Denmark) on plasma samples of patients on the first day of AMI (admission) and on samples from the identical patients collected six months following AMI. Selected miRNAs were validated by reverse transcription‑quantitative PCR (RT‑qPCR) using independent patients with AMI and a control group of patients with a stable coronary artery disease. Thirty‑two species of plasma miRNA were differentially expressed (P<0.05) on admission compared with six months following AMI. Subsequent validation in an independent patient group confirmed that miR‑133b and miR‑22‑5p were significantly up‑regulated in the serum of patients with AMI. The receiver operating characteristic (ROC) curve analysis demonstrated a diagnostic utility for miR-22-5p, which has not previously been reported to be associated with AMI. Among the selected miRNAs, miR‑22‑5p represents a novel promising biomarker for the diagnosis of AMI. PMID:27484208

  20. Ameliorative effects of boron on serum profile in buffalo (Bubalus bubalis) fed high fluoride ration.

    PubMed

    Bharti, Vijay K; Gupta, Meenakshi; Lall, D

    2008-02-01

    An experiment was undertaken to evaluate the protective role of boron on the serum profile of buffalo calves fed a high fluoride ration. Twelve male Murrah buffalo (Bubalus bubalis) calves of 6-8 months age, divided into three groups of four calves in each, were fed basal diets and supplemented with sodium fluoride (NaF, 60 ppm) alone or in combination with borax (Na2B4O7.10H2O, 140 ppm) for 90 days. Boron (B) was added in the ration as borax to make @140 ppm boron (elemental B) on DM basis in treatment II. Dietary F caused a significant (p<0.05) depressing effect on serum Ca and Zn on day 90 which was improved with B supplementation. However, serum Fe and Cu did not show any significant change on F or F+B supplementation. The serum ALP and phosphorus level were increased significantly (p<0.05) on F feeding but declined significantly (p<0.05) when B was fed. The findings suggested beneficial effect of boron on serum minerals and ALP in buffalo calves fed high fluoride ration.

  1. The future of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discovery

    PubMed Central

    Metz, Thomas O.; Zhang, Qibin; Page, Jason S.; Shen, Yufeng; Callister, Stephen J.; Jacobs, Jon M.; Smith, Richard D.

    2008-01-01

    SUMMARY 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, 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. PMID:19177179

  2. Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients.

    PubMed

    Motawi, Tarek K; Shaker, Olfat G; El-Maraghy, Shohda A; Senousy, Mahmoud A

    2015-01-01

    Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis

  3. Randomized Trial of Glucosamine and Chondroitin Supplementation on Inflammation and Oxidative Stress Biomarkers and Plasma Proteomics Profiles in Healthy Humans

    PubMed Central

    Navarro, Sandi L.; White, Emily; Kantor, Elizabeth D.; Zhang, Yuzheng; Rho, Junghyun; Song, Xiaoling; Milne, Ginger L.; Lampe, Paul D.; Lampe, Johanna W.

    2015-01-01

    Background Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans. Methods We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d) plus chondroitin sulfate (1200 mg/d) for 28 days compared to placebo in 18 (9 men, 9 women) healthy, overweight (body mass index 25.0–32.5 kg/m2) adults, aged 20–55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP), interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin. Results Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048). There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the “cytokine activity” pathway (P = 2.6 x 10-16), after glucosamine and chondroitin compared to placebo. Conclusion Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer. Trial Registration ClinicalTrials.gov NCT01682694 PMID

  4. Transcriptional profiling of whole blood: a rich source of immune biomarkers in cancer

    PubMed Central

    Saenger, Y; de Moll, E; Fu, Y

    2014-01-01

    Immunotherapy is at the forefront of cancer treatment, and biomarkers are urgently needed to predict patient response to therapy. Recently, we discovered a 4-gene peripheral blood mRNA signature for prolonged survival in patients treated with tremelimumab. Peripheral blood mRNA is a readily accessible and under-utilized source of clinically relevant biomarkers. PMID:25610728

  5. The role of developing breast cancer in alteration of serum lipid profile

    PubMed Central

    Abdelsalam, Kamal Eldin A.; Hassan, Ikhlas K.; Sadig, Isam A.

    2012-01-01

    Aims: The major aim of this study is to examine the role of alterations in lipid profile in women developing breast cancer. This study was carried out between May 2009 and December 2010. Background: The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer development in women. Materials and Methods: Plasma lipids (i.e., total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG] were analyzed from 60 controls and 120 untreated breast cancer patients with clinical and histopathological evidence, under aseptic conditions. Venous blood was drawn from the cases and controls and estimations of lipid profile were done utilizing the standard procedures. Statistical Analysis Used: Independent sample t-test to compare the mean serum levels of lipid profile and TC/HDL ratio between patients and controls. Results: A significant rise in serum total cholesterol, low-density lipoprotein cholesterol, and ratio of total cholesterol: high density lipoprotein cholesterol values, whereas high density lipoprotein cholesterol and very low density lipoprotein cholesterol were not affected significantly by the breast cancer. Conclusions: The developing breast cancer might be considered as one of the factors in alterations in lipid profile levels. PMID:23626635

  6. Temperament type specific metabolite profiles of the prefrontal cortex and serum in cattle.

    PubMed

    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.

  7. Temperament Type Specific Metabolite Profiles of the Prefrontal Cortex and Serum in Cattle

    PubMed Central

    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

  8. Salivary and serum procalcitonin and C-reactive protein as biomarkers of periodontitis in United States veterans with osteoarthritis or rheumatoid arthritis.

    PubMed

    Redman, R S; Kerr, G S; Payne, J B; Mikuls, T R; Huang, J; Sayles, H R; Becker, K L; Nylén, E S

    2016-01-01

    Serum procalcitonin (ProCT) is elevated in response to bacterial infections, whereas high sensitivity C-reactive protein (hsCRP) is a nonspecific inflammatory marker that is increased by excess adipose tissue. We examined the efficacy of ProCT and hsCRP as biomarkers of periodontitis in the saliva and serum of patients with arthritis, which is characterized by variable levels of systemic inflammation that potentially can confound the interpretation of inflammatory biomarkers. Blood and unstimulated whole saliva were collected from 33 patients with rheumatoid arthritis (RA) and 50 with osteoarthritis (OA). Periodontal status was assessed by full mouth examination and patients were categorized as having no/mild, moderate or severe periodontitis by standard parameters. Salivary and serum ProCT and hsCRP concentrations were compared. BMI, diabetes, anti-inflammatory medications and smoking status were ascertained from the patient records. Differences between OA and RA in proportionate numbers of patients were compared for race, gender, diabetes, adiposity and smoking status. Serum ProCT was significantly higher in arthritis patients with moderate to severe and severe periodontitis compared with no/mild periodontitis patients. There were no significant differences in salivary ProCT or salivary or serum hsCRP in RA patients related to periodontitis category. Most of the OA and RA patients were middle aged or older, 28.9% were diabetic, 78.3% were overweight or obese, and slightly more than half were either current or past smokers. The OA and RA groups differed by race, but not gender; blacks and males were predominant in both groups. The OA and RA groups did not differ in terms of controlled or uncontrolled diabetes, smoking status or BMI. The RA patients had been prescribed more anti-inflammatory medication than the OA patients. Our results demonstrate that circulating ProCT is a more discriminative biomarker for periodontitis than serum hsCRP in patients with

  9. Decreased saliva/serum irisin concentrations in the acute myocardial infarction promising for being a new candidate biomarker for diagnosis of this pathology.

    PubMed

    Aydin, Suna; Aydin, Suleyman; Kobat, Mehmet Ali; Kalayci, Mehmet; Eren, Mehmet Nesimi; Yilmaz, Musa; Kuloglu, Tuncay; Gul, Evrim; Secen, Ozlem; Alatas, Omer Dogan; Baydas, Adil

    2014-06-01

    Irisin is a muscle-secreted protein. Cardiac muscle produces more irisin than skeletal muscle in response to acute exercise, and is associated with myocardial infarction (MI) in an experimental model induced by isoproterenol in rats. The timing and significance of its release in patients with acute myocardial infarction (AMI) needs further investigation. We have studied the relationship between serum/saliva irisin concentration and AMI in humans. Serum and saliva samples were taken within 3 days of admission in 11 patients with AMI and in 14 matched controls. Salivary gland irisin was detected immunohistochemically, and serum and saliva levels were measured by ELISA. The three major paired salivary glands (submandibular, sublingual and parotid) produce and release irisin into saliva. Troponin-I, CK, CK-MB concentrations in the AMI group gradually increased from up to 12h, while saliva and serum irisin gradually decreased from up to 48 h, compared with the control group (P<0.05). After 12h, troponin-I, CK, CK-MB started to decrease, while saliva and serum irisin started to increase at 72 h. Serum irisin levels correlated with age, while troponin I, CK-MB, and CK were correlated and with saliva irisin in AMI patients. Besides cardiac troponin and CK-MB, irisin adds new diagnostic information in AMI patients, and the gradual decrease of saliva/serum irisin over 48 h could be a useful biomarker.

  10. Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization

    PubMed Central

    Keane, Kevin N; Hinchliffe, Peter M; Namdar, Navid; Conceicao, Jason L; Newsholme, Philip; Yovich, John L

    2015-01-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an “antiaging” therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m2) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation

  11. Novel dehydroepiandrosterone troche supplementation improves the serum androgen profile of women undergoing in vitro fertilization.

    PubMed

    Keane, Kevin N; Hinchliffe, Peter M; Namdar, Navid; Conceicao, Jason L; Newsholme, Philip; Yovich, John L

    2015-01-01

    Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in the circulation and has potent multifunctional activity. Epidemiological evidence suggests that levels of serum DHEA decrease with advancing age, and this has been associated with onset or progression of various age-related ailments, including cognitive decline and dementia, cardiovascular disease, and obesity. Consequently, these findings have sparked intense research interest in DHEA supplementation as an "antiaging" therapy. Currently, DHEA is being used by 25% of in vitro fertilization (IVF) clinicians as an adjuvant in assisted reproductive programs, yet the therapeutic benefit of DHEA is unclear. Here, we examined the use of novel DHEA-containing oral troches in patients undertaking IVF and investigated the impact of these troches on their serum androgen profile. This retrospective study determined the androgen profile of 31 IVF patients before (baseline) and after DHEA supplementation (with DHEA). Baseline serum measurements of testosterone (total and free), DHEA sulfate (DHEAS), sex hormone-binding globulin (SHBG), and androstenedione were made before and after supplementation. Each patient received DHEA troches containing 25 mg of micronized DHEA, and troches were administered sublingually twice daily for a period of no greater than 4 months. Adjuvant treatment with DHEA boosted the serum concentration of a number of androgen-related analytes, including total and free testosterone, androstenedione, and DHEAS, while serum SHBG remained unchanged. Supplementation also significantly increased the free-androgen index in IVF patients. Interestingly, the increase in serum analyte concentration following DHEA supplementation was found to be dependent on body mass index (BMI), but not individual age. Patients with the lowest BMI (<20.0 kg/m(2)) tended to have lower testosterone and DHEAS, but higher SHBG and androstenedione levels in comparison with other BMI groups postsupplementation. However

  12. Nuclear magnetic resonance-based serum metabolic profiling of dairy cows with footrot

    PubMed Central

    ZHENG, Jiasan; SUN, Lingwei; SHU, Shi; ZHU, Kuiling; XU, Chuang; WANG, Junsong; WANG, Hongbin

    2016-01-01

    Footrot is a debilitating and contagious disease in dairy cows, caused by the Gram-negative anaerobe Dichelobacter nodosus. 1H-NMR (nuclear magnetic resonance)-based metabolomics has been previously used to understand the pathology and etiology of several diseases. The objective of this study was to characterize serum from dairy cows with footrot (n=10) using 1H-NMR-based metabolomics and chemometric analyses. 1H-NMR spectroscopy with multivariate pattern recognition (principal component analysis and orthogonal partial least-squares discriminant analysis) was performed to identify biomarkers in cows with footrot (F) and healthy controls (C). 1H-NMR analysis facilitated the identification of 21 metabolites. Among these metabolites, 4 metabolites were higher and 17 metabolites were lower in the F group than in the C group. The serum levels of 5 metabolites were significantly different (P<0.05) between the two groups. The results revealed that cows with footrot have altered carbohydrate, amino acid, lipid and energy metabolic pathways. Metabolomic approaches are a clinically useful diagnostic tool for understanding the biochemical alterations and mechanisms of several diseases. PMID:27320815

  13. Assessment of BMI, Serum Leptin Levels and Lipid Profile in Patients with Skin Tags

    PubMed Central

    Sunitha, S

    2014-01-01

    Background: Skin tags (ST) are benign lesions composed of loose fibrous tissue, associated with obesity and atherogenic profile. Thus help in the follow up by considering ST as a useful cutaneous sign for the risk factor of atherosclerosis. Aim: To evaluate the association of skin tags with BMI, serum leptin and lipid profile. Materials and Methods: The study was carried out in 40 cases with ST and 40 age and gender matched controls. Subjects on oral contraceptives and systemic drugs especially lipid lowering agents, pregnant women, cases with medical history of endocrine disease, acute infection, erythroderma and psoriasis, cases with a drug history of isotretinoin use in last six months were excluded from the study. Blood samples were collected. Serum lipids and serum leptin were estimated. Result: The acrochordons group showed significantly higher values of BMI, total cholesterol (TC) and TC/HDL ratio. 60% of the patients with ST were overweight and 10% were obese. There was no statistical significant difference in leptin levels between the groups. Leptin showed a positive significant correlation with BMI in the acrochordons group. Conclusion: All the above derangements confirm that ST is cutaneous findings frequently associated with obesity and dyslipidemia. Thus follow-up of these patients with regard to the development of diseases associated with atherosclerosis may be beneficial. PMID:25386426

  14. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity.

  15. Large-Scale Glycomics of Livestock: Discovery of Highly Sensitive Serum Biomarkers Indicating an Environmental Stress Affecting Immune Responses and Productivity of Holstein Dairy Cows.

    PubMed

    Rehan, Ibrahim F; Ueda, Koichiro; Mitani, Tomohiro; Amano, Maho; Hinou, Hiroshi; Ohashi, Tetsu; Kondo, Seiji; Nishimura, Shin-Ichiro

    2015-12-01

    Because various stresses strongly influence the food productivity of livestock, biomarkers to indicate unmeasurable environmental stress in domestic animals are of increasing importance. Thermal comfort is one of the basic principles of dairy cow welfare that enhances productivity. To discover sensitive biomarkers that monitor such environmental stresses in dairy cows, we herein performed, for the first time, large-scale glycomics on 336 lactating Holstein cow serum samples over 9 months between February and October. Glycoblotting combined with MALDI-TOF/MS and DMB/HPLC allowed for comprehensive glycomics of whole serum glycoproteins. The results obtained revealed seasonal alterations in serum N-glycan levels and their structural characteristics, such as an increase in high-mannose type N-glycans in spring, the occurrence of di/triantennary complex type N-glycans terminating with two or three Neu5Gc residues in summer and autumn, and N-glycans in winter dominantly displaying Neu5Ac. A multivariate analysis revealed a correlation between the serum expression levels of these season-specific glycoforms and productivity. PMID:26595672

  16. Reduced cytosolic carboxypeptidase 6 (CCP6) level leads to accumulation of serum polyglutamylated DNAJC7 protein: A potential biomarker for renal cell carcinoma early detection

    PubMed Central

    Li, Yi; Zhu, Xiaoxiao; Ding, Juan; Ren, Shuangchun; Zhao, Heping; Wu, Song; Tian, Yong; Wang, Guo-Qing

    2016-01-01

    Renal cell carcinoma (RCC) is frequently diagnosed at advanced stages of disease, although early diagnosis has much favorable prognosis. This study assessed aberrant expression of cytosolic carboxypeptidase 6 (CCP6) leading to accumulation of serum polyglutamylated DNAJC7 as a biomarker for early RCC detection. A total of 835 RCCs, 143 chronic nephritis, 170 kidney stones and 415 health controls were collected for qRT-PCR, immunohistochemistry and Western blot analysis of CCP6 expression and mass spectrometry of DNAJC7 and polyglutamylated DNAJC7. The data showed that CCP6 expression was significantly decreased in 30 RCC tissues and that mass spectrometric and pull-down analysis identified DNAJC7 as a substrate of CCP6 and showed upregulated polyglutamylated-DNAJC7 (polyE-DNAJC7) in sera of RCC patients. The electrochemiluminescence immunoassay of large-scale serum samples from multi-institutes further confirmed the remarkable increase of polyE-DNAJC7 in 805 RCCs compared to that of 385 healthy controls (p < 0.001), 128 patients with chronic nephritis (p < 0.001), and 153 with kidney stone (p < 0.001). Serum level of DNAJC7-polyE protein was also associated with advanced RCC stage and grade in 805 patients. The data from the current study for the first time demonstrated increased serum polyglutamylated DNAJC7 as a potential biomarker for RCC early detection and association with advanced tumor stages and grade, which provides support of further polyglutamylation research in RCC. PMID:26993597

  17. Fast detection of Piscirickettsia salmonis in Salmo salar serum through MALDI-TOF-MS profiling.

    PubMed

    Olate, Verónica R; Nachtigall, Fabiane M; Santos, Leonardo S; Soto, Alex; Araya, Macarena; Oyanedel, Sandra; Díaz, Verónica; Marchant, Vanessa; Rios-Momberg, Mauricio

    2016-03-01

    Piscirickettsia salmonis is a pathogenic bacteria known as the aetiological agent of the salmonid rickettsial syndrome and causes a high mortality in farmed salmonid fishes. Detection of P. salmonis in farmed fishes is based mainly on molecular biology and immunohistochemistry techniques. These techniques are in most of the cases expensive and time consuming. In the search of new alternatives to detect the presence of P. salmonis in salmonid fishes, this work proposed the use of MALDI-TOF-MS to compare serum protein profiles from Salmo salar fish, including experimentally infected and non-infected fishes using principal component analysis (PCA). Samples were obtained from a controlled bioassay where S. salar was challenged with P. salmonis in a cohabitation model and classified according to the presence or absence of the bacteria by real time PCR analysis. MALDI spectra of the fish serum samples showed differences in its serum protein composition. These differences were corroborated with PCA analysis. The results demonstrated that the use of both MALDI-TOF-MS and PCA represents a useful tool to discriminate the fish status through the analysis of salmonid serum samples. PMID:26956387

  18. LC/MS lipid profiling from human serum: a new method for global lipid extraction.

    PubMed

    Pellegrino, Roberto Maria; Di Veroli, Alessandra; Valeri, Aurora; Goracci, Laura; Cruciani, Gabriele

    2014-12-01

    Over the last decade, technological advances have improved the sensitivity and selectivity of LC/MS analyzers, providing very efficient tools for lipidomics research. In particular, the nine lipid classes that constitute 99 % of the human serum lipidome (sterols, cholesteryl esters, phosphocholines, phosphoethanolamines, sphingomyelins, triacylglycerols, fatty acids, lysophosphocholines, and diacylglycerols) can be easily detected. However, until today there has not been a unique technique for sample preparation that provides a satisfactory recovery for all of these nine classes together. In this work, we have developed and validated a new one-phase extraction (OPE) method that overcomes this limitation. This method was also compared with the gold standard lipid extraction methods such as Folch, Bligh & Dyer, and recently developed methods with methanol and methyl-tert-butyl ether. Results demonstrate that the mixture of methanol/chloroform/MTBE (MMC) provides a recovery very close to 100 % for all nine lipid classes of the human serum investigated. For this extraction method, 100 μL of human serum is incubated with 2 mL of the solvents mixture, then vortexed and centrifuged. For its simplicity of execution, rapidity, reproducibility, and the reduced volume of sample required, this method opens the door to the use of human serum lipid profiling for large-scale applications in scientific research and clinical trials.

  19. Perspectives on using des-γ-carboxyprothrombin (DCP) as a serum biomarker: facilitating early detection of hepatocellular carcinoma in China.

    PubMed

    Song, Peipei; Feng, Xiaobin; Zhang, Keming; Song, Tianqiang; Ma, Kuansheng; Kokudo, Norihiro; Dong, Jiahong; Tang, Wei

    2013-08-01

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths in China. Evidence has shown that surgical resection and liver transplantation may offer the best potential for treating HCC but are only available to patients whose tumors are detected early. Over the past few decades, although a series of measures for standardized management of HCC has been implemented in China, most patients with HCC in China still present with advanced-stage disease, thus strategies to screen for and diagnose HCC at an earlier stage are urgently needed in China when curable interventions can be offered to achieve long-term disease-free survival for patients with HCC. In China, the serum biomarker α-fetoprotein (AFP) is considered a useful and feasible tool for HCC screening and early diagnosis. However, the sensitivity and specificity of AFP vary widely, and the total AFP is not always specific, especially when HCC is in its early stages. Globally, numerous studies have reported that the combination of des-γ-carboxyprothrombin (DCP)