Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

KAUST Repository

Mansour, Hicham

2014-08-27

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Biomarkers for Detecting Mitochondrial Disorders

Directory of Open Access Journals (Sweden)

Josef Finsterer

2018-01-01

Full Text Available (1 Objectives: Mitochondrial disorders (MIDs are a genetically and phenotypically heterogeneous group of slowly or rapidly progressive disorders with onset from birth to senescence. Because of their variegated clinical presentation, MIDs are difficult to diagnose and are frequently missed in their early and late stages. This is why there is a need to provide biomarkers, which can be easily obtained in the case of suspecting a MID to initiate the further diagnostic work-up. (2 Methods: Literature review. (3 Results: Biomarkers for diagnostic purposes are used to confirm a suspected diagnosis and to facilitate and speed up the diagnostic work-up. For diagnosing MIDs, a number of dry and wet biomarkers have been proposed. Dry biomarkers for MIDs include the history and clinical neurological exam and structural and functional imaging studies of the brain, muscle, or myocardium by ultrasound, computed tomography (CT, magnetic resonance imaging (MRI, MR-spectroscopy (MRS, positron emission tomography (PET, or functional MRI. Wet biomarkers from blood, urine, saliva, or cerebrospinal fluid (CSF for diagnosing MIDs include lactate, creatine-kinase, pyruvate, organic acids, amino acids, carnitines, oxidative stress markers, and circulating cytokines. The role of microRNAs, cutaneous respirometry, biopsy, exercise tests, and small molecule reporters as possible biomarkers is unsolved. (4 Conclusions: The disadvantages of most putative biomarkers for MIDs are that they hardly meet the criteria for being acceptable as a biomarker (missing longitudinal studies, not validated, not easily feasible, not cheap, not ubiquitously available and that not all MIDs manifest in the brain, muscle, or myocardium. There is currently a lack of validated biomarkers for diagnosing MIDs.

Omega-6 fatty acid biomarkers and incident type 2 diabetes: Pooled analysis of individual-level data for 39740 adults from 20 prospective cohort studies

Science.gov (United States)

The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2...

Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites

International Nuclear Information System (INIS)

Louisse, Jochem; Bai Yanqing; Verwei, Miriam; Sandt, Johannes J.M. van de; Blaauboer, Bas J.; Rietjens, Ivonne M.C.M.

2010-01-01

Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA) metabolite of ethylene glycol monomethyl ether as the model compound. The results obtained demonstrate an MAA-induced decrease of the intracellular pH (pH i ) of embryonic BALB/c-3T3 cells as well as of embryonic stem (ES)-D3 cells, at concentrations that affect ES-D3 cell differentiation. These results suggest a mechanism for MAA-mediated embryotoxicity similar to the mechanism of embryotoxicity of the drugs valproic acid and acetazolamide (ACZ), known to decrease the pH i in vivo, and therefore used as positive controls. The embryotoxic alkoxyacetic acid metabolites ethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid also caused an intracellular acidification of BALB/c-3T3 cells at concentrations that are known to inhibit ES-D3 cell differentiation. Two other embryotoxic compounds, all-trans-retinoic acid and 5-fluorouracil, did not decrease the pH i of embryonic cells at concentrations that affect ES-D3 cell differentiation, pointing at a different mechanism of embryotoxicity of these compounds. MAA and ACZ induced a concentration-dependent inhibition of ES-D3 cell differentiation, which was enhanced by amiloride, an inhibitor of the Na + /H + -antiporter, corroborating an important role of the pH i in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH i may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

Science.gov (United States)

Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

2010-10-01

Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

Biomarker Research in Parkinson's Disease Using Metabolite Profiling

DEFF Research Database (Denmark)

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

2017-01-01

Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifa......) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD......., the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan...

Omega-6 fatty acid biomarkers and incident type 2 diabetes : pooled analysis of individual-level data for 39 740 adults from 20 prospective cohort studies

NARCIS (Netherlands)

Wu, Jason H.Y.; Marklund, Matti; Imamura, Fumiaki; Tintle, Nathan; Ardisson Korat, Andres V.; de Goede, Janette; Zhou, Xia; Yang, Wei Sin; de Oliveira Otto, Marcia C.; Kröger, Janine; Qureshi, Waqas; Virtanen, Jyrki K.; Bassett, Julie K.; Frazier-Wood, Alexis C.; Lankinen, Maria; Murphy, Rachel A.; Rajaobelina, Kalina; Del Gobbo, Liana C.; Forouhi, Nita G.; Luben, Robert; Khaw, Kay Tee; Wareham, Nick; Kalsbeek, Anya; Veenstra, Jenna; Luo, Juhua; Hu, Frank B.; Lin, Hung Ju; Siscovick, David S.; Boeing, Heiner; Chen, Tzu An; Steffen, Brian; Steffen, Lyn M.; Hodge, Allison; Eriksdottir, Gudny; Smith, Albert V.; Gudnason, Vilmunder; Harris, Tamara B.; Brouwer, Ingeborg A.; Berr, Claudine; Helmer, Catherine; Samieri, Cecilia; Laakso, Markku; Tsai, Michael Y.; Giles, Graham G.; Nurmi, Tarja; Wagenknecht, Lynne; Schulze, Matthias B.; Lemaitre, Rozenn N.; Chien, Kuo Liong; Soedamah-Muthu, Sabita S.; Geleijnse, Johanna M.; Sun, Qi; Harris, William S.; Lind, Lars; Ärnlöv, Johan; Riserus, Ulf; Micha, Renata; Mozaffarian, Dariush

2017-01-01

Background The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with

Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys.

Science.gov (United States)

Shen, Hong; Nelson, David M; Oliveira, Regina V; Zhang, Yueping; Mcnaney, Colleen A; Gu, Xiaomei; Chen, Weiqi; Su, Ching; Reily, Michael D; Shipkova, Petia A; Gan, Jinping; Lai, Yurong; Marathe, Punit; Humphreys, W Griffith

2018-02-01

Perturbation of organic anion transporter (OAT) 1- and OAT3-mediated transport can alter the exposure, efficacy, and safety of drugs. Although there have been reports of the endogenous biomarkers for OAT1/3, none of these have all of the characteristics required for a clinical useful biomarker. Cynomolgus monkeys were treated with intravenous probenecid (PROB) at a dose of 40 mg/kg in this study. As expected, PROB increased the area under the plasma concentration-time curve (AUC) of coadministered furosemide, a known substrate of OAT1 and OAT3, by 4.1-fold, consistent with the values reported in humans (3.1- to 3.7-fold). Of the 233 plasma metabolites analyzed using a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics method, 29 metabolites, including pyridoxic acid (PDA) and homovanillic acid (HVA), were significantly increased after either 1 or 3 hours in plasma from the monkeys pretreated with PROB compared with the treated animals. The plasma of animals was then subjected to targeted LC-MS/MS analysis, which confirmed that the PDA and HVA AUCs increased by approximately 2- to 3-fold by PROB pretreatments. PROB also increased the plasma concentrations of hexadecanedioic acid (HDA) and tetradecanedioic acid (TDA), although the increases were not statistically significant. Moreover, transporter profiling assessed using stable cell lines constitutively expressing transporters demonstrated that PDA and HVA are substrates for human OAT1, OAT3, OAT2 (HVA), and OAT4 (PDA), but not OCT2, MATE1, MATE2K, OATP1B1, OATP1B3, and sodium taurocholate cotransporting polypeptide. Collectively, these findings suggest that PDA and HVA might serve as blood-based endogenous probes of cynomolgus monkey OAT1 and OAT3, and investigation of PDA and HVA as circulating endogenous biomarkers of human OAT1 and OAT3 function is warranted. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Identification of a potential biomarker panel for the intake of the common dietary trans fat elaidic acid (trans∆9-C18:1)

DEFF Research Database (Denmark)

Kroager, Toke Peter; Nielsen, Lone Vendel; Bak, Steffen

2012-01-01

system, and the cells were maintained for seven days in serum-free medium containing 100 μM elaidic acid (trans∆9-C18:1), oleic acid (cis∆9-C18:1) or stearic acid (C18:0). The secretomes were analyzed by stable isotope labeling of amino acids in cell culture (SILAC), difference in gel electrophoresis......Trans fatty acid intake has been correlated to an unfavorable plasma lipoprotein profile and an increased cardiovascular disease risk. The present study aimed to identify a plasma protein biomarker panel related to human intake of elaidic acid. The human liver cell line HepG2-SF was used as a model...

Oxidative stress biomarkers in Oreochromis niloticus as early ...

African Journals Online (AJOL)

2018-04-10

Apr 10, 2018 ... warning signals in assessing pollution from acid mine drainage and ... fish species Oreochromis niloticus as a bio-indicator organism in active ... Key water quality parameters, including ... Biomarkers can provide early warning of potential higher- ...... CT (2001) The use of biomarkers in Ecological Risk.

Multiple Sclerosis Cerebrospinal Fluid Biomarkers

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Gavin Giovannoni

2006-01-01

Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

Serum and Plasma Metabolomic Biomarkers for Lung Cancer.

Science.gov (United States)

Kumar, Nishith; Shahjaman, Md; Mollah, Md Nurul Haque; Islam, S M Shahinul; Hoque, Md Aminul

2017-01-01

In drug invention and early disease prediction of lung cancer, metabolomic biomarker detection is very important. Mortality rate can be decreased, if cancer is predicted at the earlier stage. Recent diagnostic techniques for lung cancer are not prognosis diagnostic techniques. However, if we know the name of the metabolites, whose intensity levels are considerably changing between cancer subject and control subject, then it will be easy to early diagnosis the disease as well as to discover the drug. Therefore, in this paper we have identified the influential plasma and serum blood sample metabolites for lung cancer and also identified the biomarkers that will be helpful for early disease prediction as well as for drug invention. To identify the influential metabolites, we considered a parametric and a nonparametric test namely student׳s t-test as parametric and Kruskal-Wallis test as non-parametric test. We also categorized the up-regulated and down-regulated metabolites by the heatmap plot and identified the biomarkers by support vector machine (SVM) classifier and pathway analysis. From our analysis, we got 27 influential (p-value<0.05) metabolites from plasma sample and 13 influential (p-value<0.05) metabolites from serum sample. According to the importance plot through SVM classifier, pathway analysis and correlation network analysis, we declared 4 metabolites (taurine, aspertic acid, glutamine and pyruvic acid) as plasma biomarker and 3 metabolites (aspartic acid, taurine and inosine) as serum biomarker.

Identification of trophic interactions within an estuarine food web (northern New Zealand) using fatty acid biomarkers and stable isotopes

Science.gov (United States)

Alfaro, Andrea C.; Thomas, François; Sergent, Luce; Duxbury, Mark

2006-10-01

Fatty acid biomarkers and stable isotope signatures were used to identify the trophic dynamics of a mangrove/seagrass estuarine food web at Matapouri, northern New Zealand. Specific fatty acids were used to identify the preferred food sources (i.e., mangroves, seagrass, phytoplankton, macroalgae, bacteria, and zooplankton) of dominant fauna (i.e., filter feeders, grazing snails, scavenger/predatory snails, shrimp, crabs, and fish), and their presence in water and sediment samples throughout the estuary. The diets of filter feeders were found to be dominated by dinoflagellates, whereas grazers showed a higher diatom contribution. Bacteria associated with organic debris on surface sediments and brown algal ( Hormosira banksii) material in the form of suspended organic matter also accounted for a high proportion of most animal diets. Animals within higher trophic levels had diverse fatty acid profiles, revealing their varied feeding strategies and carbon sources. The stable isotope (δ 13C and δ 15N) analyses of major primary producers and consumers/predators revealed a trend of 15N enrichment with increasing trophic level, while δ 13C values provided a generally good description of carbon flow through the food web. Overall results from both fatty acid profiles and stable isotopes indicate that a variety of carbon sources with a range of trophic pathways typify this food web. Moreover, none of the animals studied was dependent on a single food source. This study is the first to use a comprehensive fatty acid biomarker and stable isotope approach to investigate the food web dynamics within a New Zealand temperate mangrove/seagrass estuary. This quantitative research may contribute to the currently developing management strategies for estuaries in northern New Zealand, especially for those perceived to have expanding mangrove fringes.

Sediment Origin Determination in the Sub-Catchment of Mistelbach (Austria) using Fatty Acids Biomarkers and Compound-Specific Stable Isotope Techniques

International Nuclear Information System (INIS)

Mabit, L.; Chen, X.; Resch, C.; Toloza, A.; Meusburger, K.; Alewell, C.; Gibbs, M.; Klik, A.; Eder, A.; Strauss, P.

2016-01-01

Compound-specific stable isotope (CSSI) signatures of inherent soil organic biomarkers allow discriminating and apportioning the source of soil contribution from different land uses. Plant communities label the soil where they grow by exuding organic biomarkers. Although all plants produce the same biomarkers, the stable isotopic signature of those biomarkers is different for each plant species. For agri-environmental investigations, the CSSI technique is based on the measurement of carbon-13 ( 13 C) natural abundance signatures of specific organic compounds such as natural fatty acids (FAs) in the soil. By linking fingerprints of land use to the sediment in deposition zones, this approach has been shown to be a useful technique for determining the source of eroded soil and thereby identifying areas prone to soil degradation. The authors have used this innovative technique to investigate a 3 hectares sub-catchment of Mistelbach situated 60 km north of Vienna. Using the 137 Cs technique, Mabit et al. (2009) reported a local maximum sedimentation rate reaching 20 to 50 t ha -1 yr -1 in the lowest part of this Austrian catchment. To test the ability of the CSSI technique to discriminate different sediment sources of these deposited sediments, representative soil samples from four main agricultural fields of the site were analyzed

Kadar Asam Urat Serum sebagai Biomarker Preeklamsi

Directory of Open Access Journals (Sweden)

Neli Sumanti

2013-06-01

Full Text Available Preeclampsia remains a health problem that becomes one of the causes of maternal deaths besides bleeding and infection. The etiology and pathogenesis of preeclampsia are unclear. Increased serum uric acid levels is seen simultaneously with the increase of blood pressure and occurred before the onset of proteinuria. Therefore, the uric acid can be used as a biomarker. The aim of this study was to analyze the serum uric acid levels between normal and preeclampsia pregnancies. The study was conducted in Dr.Hasan Sadikin Hospital Bandung between March and May 2011, using cross sectional study design. Subjects were 45 inpartu normal pregnant women as control and 44 in partu pregnant women with preeclampsia accordance with inclusion and exclusion criteria. Levels of uric acid in normal pregnancy are 3,43 ±0.14 mg/dL. In this study uric acid levels resulting in cut-off levels of 4,8 mg/dL with a sensitivity value of 93%, and specificity 80%. Conclusions: uric acid levels in at term preeclampsia are higher compared with normal pregnancies. Increased levels of uric acid can be considered as one of biomarkers of preeclampsia, hence the serum uric acid levels used as serial examinations in pregnant women during antenatal care.

Plasma elaidic acid level as biomarker of industrial trans fatty acids and risk of weight change: report from the EPIC study.

Science.gov (United States)

Chajès, Véronique; Biessy, Carine; Ferrari, Pietro; Romieu, Isabelle; Freisling, Heinz; Huybrechts, Inge; Scalbert, Augustin; Bueno de Mesquita, Bas; Romaguera, Dora; Gunter, Marc J; Vineis, Paolo; Hansen, Camilla Plambeck; Jakobsen, Marianne Uhre; Clavel-Chapelon, Françoise; Fagherazzi, Guy; Boutron-Ruault, Marie-Christine; Katzke, Verana; Neamat-Allah, Jasmine; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Naska, Androniki; Orfanos, Philippos; Pala, Valeria; Masala, Giovanna; Mattiello, Amalia; Skeie, Guri; Weiderpass, Elisabete; Agudo, Antonio; Huerta, Jose Maria; Ardanaz, Eva; Sánchez, Maria Jose; Dorronsoro, Miren; Quirós, Jose Ramon; Johansson, Ingegerd; Winkvist, Anna; Sonested, Emily; Key, Tim; Khaw, Kay-Tee; Wareham, Nicolas J; Peeters, Petra H M; Slimani, Nadia

2015-01-01

Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Baseline plasma fatty acid concentrations were determined in a representative EPIC sample from the 23 participating EPIC centers. A total of 1,945 individuals were followed for a median of 4.9 years to monitor weight change. The association between elaidic acid level and percent change of weight was investigated using a multinomial logistic regression model, adjusted by length of follow-up, age, energy, alcohol, smoking status, physical activity, and region. In women, doubling elaidic acid was associated with a decreased risk of weight loss (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.55-0.88, p = 0.002) and a trend was observed with an increased risk of weight gain during the 5-year follow-up (OR = 1.23, 95% CI = 0.97-1.56, p = 0.082) (p-trendacid level and risk of weight loss (OR = 0.82, 95% CI = 0.66-1.01, p = 0.062) while no significant association was found with risk of weight gain during the 5-year follow-up (OR = 1.08, 95% CI = 0.88-1.33, p = 0.454). No association was found for saturated and cis-monounsaturated fatty acids. These data suggest that a high intake of industrial trans fatty acids may decrease the risk of weight loss, particularly in women. Prevention of obesity should consider limiting the consumption of highly processed foods, the main source of industrially-produced trans fatty acids.

Chiral Biomarkers in Meteorites

Science.gov (United States)

Hoover, Richard B.

2010-01-01

The chirality of organic molecules with the asymmetric location of group radicals was discovered in 1848 by Louis Pasteur during his investigations of the rotation of the plane of polarization of light by crystals of sodium ammonium paratartrate. It is well established that the amino acids in proteins are exclusively Levorotary (L-aminos) and the sugars in DNA and RNA are Dextrorotary (D-sugars). This phenomenon of homochirality of biological polymers is a fundamental property of all life known on Earth. Furthermore, abiotic production mechanisms typically yield recemic mixtures (i.e. equal amounts of the two enantiomers). When amino acids were first detected in carbonaceous meteorites, it was concluded that they were racemates. This conclusion was taken as evidence that they were extraterrestrial and produced by abiologically. Subsequent studies by numerous researchers have revealed that many of the amino acids in carbonaceous meteorites exhibit a significant L-excess. The observed chirality is much greater than that produced by any currently known abiotic processes (e.g. Linearly polarized light from neutron stars; Circularly polarized ultraviolet light from faint stars; optically active quartz powders; inclusion polymerization in clay minerals; Vester-Ulbricht hypothesis of parity violations, etc.). This paper compares the measured chirality detected in the amino acids of carbonaceous meteorites with the effect of these diverse abiotic processes. IT is concluded that the levels observed are inconsistent with post-arrival biological contamination or with any of the currently known abiotic production mechanisms. However, they are consistent with ancient biological processes on the meteorite parent body. This paper will consider these chiral biomarkers in view of the detection of possible microfossils found in the Orgueil and Murchison carbonaceous meteorites. Energy dispersive x-ray spectroscopy (EDS) data obtained on these morphological biomarkers will be

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies

OpenAIRE

Birech, Zephania; Mwangi, Peter Waweru; Bukachi, Fredrick; Mandela, Keith Makori

2017-01-01

Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectros...

Fluorescent detection of dipicolinic acid as a biomarker of bacterial spores using lanthanide-chelated gold nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Donmez, Mert [Department of Chemistry, Faculty of Art and Sciences, Duzce University, Duzce 81620 (Turkey); Yilmaz, M. Deniz, E-mail: deniz.yilmaz@gidatarim.edu.tr [Department of Bioengineering, Faculty of Engineering and Architecture, Konya Food and Agriculture University, Konya 42080 (Turkey); Kilbas, Benan, E-mail: benankilbas@duzce.edu.tr [Department of Chemistry, Faculty of Art and Sciences, Duzce University, Duzce 81620 (Turkey)

2017-02-15

Highlights: • The nanosensors based on gold nanoparticles functionalized with lanthanide complexes were synthesized. • The nanosensors selectively and sensitively detected DPA, a biomarker of bacterial spores. • Ratiometric sensing of DPA by a ternary complex was achieved by ligand displacement strategy. - Abstract: Gold nanoparticles (GNPs) functionalized with ethylenediamine-lanthanide complexes (Eu-GNPs and Tb-GNPs) were used for the selective fluorescent detection of dipicolinic acid (DPA), a unique biomarker of bacterial spores, in water. Particles were characterized by transmission electron microscopy and zeta potential measurements. The coordination of DPA to the lanthanides resulted in the enhancement of the fluorescence. A selective response to DPA was observed over the nonselective binding of aromatic ligands. The ligand displacement strategy were also employed for the ratiometric fluorescent detection of DPA. 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedion (TFNB) was chosen as an antenna to synthesize ternary complexes. The addition of DPA on EuGNP:TFNB ternary complex quenched the initial emission of the complex at 615 nm and increased the TFNB emission at 450 nm when excited at 350 nm. The results demonstrated that the ratiometric fluorescent detection of DPA was achieved by ligand displacement strategy.

Biomarkers in pancreatic adenocarcinoma: current perspectives.

Science.gov (United States)

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

Biomarkers in pancreatic adenocarcinoma: current perspectives

Directory of Open Access Journals (Sweden)

Swords DS

2016-12-01

Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.

Science.gov (United States)

Birech, Zephania; Mwangi, Peter Waweru; Bukachi, Fredrick; Mandela, Keith Makori

2017-01-01

Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.)Chiov. Sprague Dawley (SD) rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1), leucine (1106, 1248, 1302, 1395 cm-1) and isolecucine (1108, 1248, 1437 and 1585 cm-1) were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.)Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1), leucine (1395 cm-1) and isoleucine (1437 cm-1) in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds) diabetes and pre-diabetes screening in blood (human or rat's) with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing comparative

Application of Raman spectroscopy in type 2 diabetes screening in blood using leucine and isoleucine amino-acids as biomarkers and in comparative anti-diabetic drugs efficacy studies.

Directory of Open Access Journals (Sweden)

Zephania Birech

Full Text Available Diabetes is an irreversible condition characterized by elevated blood glucose levels. Currently, there are no predictive biomarkers for this disease and the existing ones such as hemoglobin A1c and fasting blood glucose are used only when diabetes symptoms are noticed. The objective of this work was first to explore the potential of leucine and isoleucine amino acids as diabetes type 2 biomarkers using their Raman spectroscopic signatures. Secondly, we wanted to explore whether Raman spectroscopy can be applied in comparative efficacy studies between commercially available anti-diabetic drug pioglitazone and the locally used anti-diabetic herbal extract Momordica spinosa (Gilg.Chiov. Sprague Dawley (SD rat's blood was used and were pipetted onto Raman substrates prepared from conductive silver paste smeared glass slides. Prominent Raman bands associated with glucose (926, 1302, 1125 cm-1, leucine (1106, 1248, 1302, 1395 cm-1 and isolecucine (1108, 1248, 1437 and 1585 cm-1 were observed. The Raman bands centered at 1125 cm-1, 1395 cm-1 and 1437 cm-1 associated respectively to glucose, leucine and isoleucine were chosen as biomarker Raman peaks for diabetes type 2. These Raman bands displayed decreased intensities in blood from diabetic SD rats administered antidiabetic drugs pioglitazone and herbal extract Momordica spinosa (Gilg.Chiov. The intensity decrease indicated reduced concentration levels of the respective biomarker molecules: glucose (1125 cm-1, leucine (1395 cm-1 and isoleucine (1437 cm-1 in blood. The results displayed the power and potential of Raman spectroscopy in rapid (10 seconds diabetes and pre-diabetes screening in blood (human or rat's with not only glucose acting as a biomarker but also leucine and isoleucine amino-acids where intensities of respectively assigned bands act as references. It also showed that using Raman spectroscopic signatures of the chosen biomarkers, the method can be an alternative for performing

Oxidative stress biomarkers in different tissues of rainbow trout (Oncorhynchus mykiss exposed to Disinfectant-CIP formulated with peracetic acid and hydrogen peroxide

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Tkachenko Halyna

2014-09-01

Full Text Available The aim of study was to determine the effects of exposure to the product DEZYNFEKTANT-CIP (Eng. - Disinfectant-CIP, which is formulated with peracetic acid and hydrogen peroxide, on oxidative stress biomarkers (lipid peroxidation (LPO levels and the carbonyl content of oxidatively modified proteins and antioxidant defenses (superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, total antioxidant capacity in muscle, gill, hepatic, and cardiac tissues of rainbow trout, Oncorhynchus mykiss (Walbaum. LPO and carbonyl contents changed with tissue type. Exposure to Disinfectant-CIP led to a significant decrease in LPO in muscle tissues and carbonyl content in muscle and gill tissues. The inhibition of SOD and CAT activity in muscle, hepatic, and cardiac tissues was observed probably because of increased oxidative stress during disinfection; however, hepatic and cardiac GPx activity increased in an attempt to counteract oxidative stress. We suggest that oxidative stress during the oxidation of peracetic acid and hydrogen peroxide could be counteracted by the antioxidant system in trout tissues. Correlative analysis between oxidative stress biomarkers and antioxidant defense confirms the pivotal role of SOD and CAT against CIP-induced oxidative stress

Preservation of terrestrial plant biomarkers from Nachukui Formation sediments and their viability for stable isotope analysis

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Kahle, E.; Uno, K. T.; Polissar, P. J.; Lepre, C. J.; deMenocal, P. B.

2013-12-01

Plio-Pleistocene sedimentary records from the Turkana Basin in eastern Africa provide a unique opportunity to compare a high-resolution record of climate and terrestrial vegetation with important changes in the record of human evolution. Molecular biomarkers from terrestrial vegetation can yield stable isotope ratios of hydrogen and carbon that reflect ancient climate and vegetation. However, the preservation of long-chain plant wax biomarkers in these paleosol, fluvial, and lacustrine sediments is not known, and this preservation must be studied to establish their utility for molecular stable isotope studies. We investigated leaf wax biomarkers in Nachukui Formation sediments deposited between 2.3 and 1.7 Ma to assess biomarker preservation. We analyzed n alkane and n alkanoic acid concentrations and, where suitable, molecular carbon and hydrogen isotope ratios. Molecular abundance distributions show a great deal of variance in biomarker preservation and plant-type source as indicated by the carbon preference index and average chain length. This variation suggests that some samples are suitable for isotopic analysis, while other samples lack primary terrestrial plant biomarker signatures. The biomarker signal in many samples contains significant additional material from unidentified sources. For example, the n-alkane distributions contain an unresolved complex mixture underlying the short and mid-chain n-alkanes. Samples from lacustrine intervals include long-chain diacids, hydroxy acids and (ω-1) ketoacids that suggest degradation of the original acids. Degradation of poorly preserved samples and the addition of non-terrestrial plant biomarkers may originate from a number of processes including forest fire or microbial alteration. Isotopic analysis of well-preserved terrestrial plant biomarkers will be presented along with examples where the original biomarker distribution has been altered.

Determination of gouty arthritis' biomarkers in human urine using reversed-phase high-performance liquid chromatography

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Lei-Wen Xiang

2014-04-01

Full Text Available Creatinine, uric acid, hypoxanthine and xanthine are important diagnostic biomarkers in human urine for gouty arthritis or renal disease diacrisis. A simple method for simultaneous determination of these biomarkers in urine based on reversed-phase high-performance liquid chromatography (RP-HPLC with ultraviolet (UV detector was proposed. After pretreatment by dilution, centrifugation and filtration, the biomarkers in urine samples were separated by ODS-BP column by elution with methanol/50 mM NaH2PO4 buffer solution at pH 5.26 (5:95. Good linearity between peak areas and concentrations of standards was obtained for the biomarkers with correlation coefficients in the range of 0.9957–0.9993. The proposed analytical method has satisfactory repeatability (the recovery of data in a range of creatinine, uric acid, hypoxanthine and xanthine was 93.49–97.90%, 95.38–96.45%, 112.46–115.78% and 90.82–97.13% with standard deviation of <5%, respectively and the limits of detection (LODs, S/N≥3 for creatinine, uric acid, hypoxanthine, and xanthine were 0.010, 0.025, 0.050 and 0.025 mg/L, respectively. The established method was proved to be simple, accurate, sensitive and reliable for the quantitation of gouty arthritis' biomarkers in human urine samples. The ratio of creatinine to uric acid was found to be a possible factor for assessment of gouty arthritis. Keywords: Gouty arthritis, Creatinine, Uric acid, Hypoxanthine, Xanthine, High-performance liquid chromatography

Calcium-deficiency assessment and biomarker identification by an integrated urinary metabonomics analysis

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2013-01-01

Background Calcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency. Methods The metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans. Results Urinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson

Short-term variability in biomarkers of bone metabolism in sheep.

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Sousa, Cristina P; de Azevedo, Jorge T; Reis, Rui L; Gomes, Manuela E; Dias, Isabel R

2014-01-01

Changes in bone remodeling during pathological states and during their treatment can be assessed noninvasively by measuring biomarkers of bone metabolism. Their application is limited, however, by the potential biological variability in the levels of these biomarkers over time. To determine the short-term variability in biomarkers of bone metabolism in adult sheep, the authors measured serum levels of alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N-terminal propeptide of type-III procollagen (PIIINP), deoxypyridinoline (DPD), tartrate-resistant acid phosphatase (TRAP), calcium and phosphorus intermittently over a 12-week period. There were significant differences in mean ALP activity and in phosphorus concentrations over time, but all other biomarkers showed no significant short-term variability. The results suggest that biomarkers of bone metabolism in sheep, especially the bone resorption marker DPD and the bone formation marker BALP, can be used reliably to detect changes in bone cellular activity.

Polymethylene-interrupted fatty acids: Biomarkers for native and exotic mussels in the Laurentian Great Lakes

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Mezek, Tadej; Sverko, Ed; Ruddy, Martina D.; Zaruk, Donna; Capretta, Alfredo; Hebert, Craig E.; Fisk, Aaron T.; McGoldrick, Daryl J.; Newton, Teresa J.; Sutton, Trent M.; Koops, Marten A.; Muir, Andrew M.; Johnson, Timothy B.; Ebener, Mark P.; Arts, Michael T.

2011-01-01

Freshwater organisms synthesize a wide variety of fatty acids (FAs); however, the ability to synthesize and/or subsequently modify a particular FA is not universal, making it possible to use certain FAs as biomarkers. Herein we document the occurrence of unusual FAs (polymethylene-interrupted fatty acids; PMI-FAs) in select freshwater organisms in the Laurentian Great Lakes. We did not detect PMI-FAs in: (a) natural seston from Lake Erie and Hamilton Harbor (Lake Ontario), (b) various species of laboratory-cultured algae including a green alga (Scenedesmus obliquus), two cyanobacteria (Aphanizomenon flos-aquae and Synechococystis sp.), two diatoms (Asterionella formosa, Diatoma elongatum) and a chrysophyte (Dinobryon cylindricum) or, (c) zooplankton (Daphnia spp., calanoid or cyclopoid copepods) from Lake Ontario, suggesting that PMI-FAs are not substantively incorporated into consumers at the phytoplankton–zooplankton interface. However, these unusual FAs comprised 4-6% of total fatty acids (on a dry tissue weight basis) of native fat mucket (Lampsilis siliquoidea) and plain pocketbook (L. cardium) mussels and in invasive zebra (Dreissena polymorpha) and quagga (D. bugensis) mussels. We were able to clearly partition Great Lakes' mussels into three separate groups (zebra, quagga, and native mussels) based solely on their PMI-FA profiles. We also provide evidence for the trophic transfer of PMI-FAs from mussels to various fishes in Lakes Ontario and Michigan, further underlining the potential usefulness of PMI-FAs for tracking the dietary contribution of mollusks in food web and contaminant-fate studies.

Feeding ecology of mesopelagic zooplankton of the subtropical and subarctic North Pacific Ocean determined with fatty acid biomarkers

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Wilson, S. E.; Steinberg, D. K.; Chu, F.-L. E.; Bishop, J. K. B.

2010-10-01

Mesopelagic zooplankton may meet their nutritional and metabolic requirements in a number of ways including consumption of sinking particles, carnivory, and vertical migration. How these feeding modes change with depth or location, however, is poorly known. We analyzed fatty acid (FA) profiles to characterize zooplankton diet and large particle (>51 μm) composition in the mesopelagic zone (base of euphotic zone -1000 m) at two contrasting time-series sites in the subarctic (station K2) and subtropical (station ALOHA) Pacific Ocean. Total FA concentration was 15.5 times higher in zooplankton tissue at K2, largely due to FA storage by seasonal vertical migrators such as Neocalanus and Eucalanus. FA biomarkers specific to herbivory implied a higher plant-derived food source at mesotrophic K2 than at oligotrophic ALOHA. Zooplankton FA biomarkers specific to dinoflagellates and diatoms indicated that diatoms, and to a lesser extent, dinoflagellates were important food sources at K2. At ALOHA, dinoflagellate FAs were more prominent. Bacteria-specific FA biomarkers in zooplankton tissue were used as an indicator of particle feeding, and peaks were recorded at depths where known particle feeders were present at ALOHA (e.g., ostracods at 100-300 m). In contrast, depth profiles of bacterial FA were relatively constant with depth at K2. Diatom, dinoflagellate, and bacterial biomarkers were found in similar proportions in both zooplankton and particles with depth at both locations, providing additional evidence that mesopelagic zooplankton consume sinking particles. Carnivory indices were higher and increased significantly with depth at ALOHA, and exhibited distinct peaks at K2, representing an increase in dependence on other zooplankton for food in deep waters. Our results indicate that feeding ecology changes with depth as well as by location. These changes in zooplankton feeding ecology from the surface through the mesopelagic zone, and between contrasting environments

Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

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Wilhelm, M. B.; Davila, A. F.; Eigenbrode, J. L.; Parenteau, M. N.; Jahnke, L. L.; Summons, R. E.; Liu, X.; Wray, J. J.; Stamos, B.; O'Reilly, S. S.; Williams, A. J.

2015-12-01

Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at ~2 m depth (~750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of lipid biomarker

Preservation of Lipid Biomarkers Under Prolonged and Extreme Hyperaridity in Atacama Desert Soils

Science.gov (United States)

Wilhelm, Mary Beth

2015-01-01

Molecular biomarkers are the most direct biosignatures of life on early Earth and a key target in the search for life on Mars. Lipid biomarkers are of particular interest given their ability to survive oxidative degradation and record microbial presence and activity of microorganisms that occurred billions of years ago (Eigenbrode, 2008). Environmental conditions that suspend biotic and abiotic degradative processes prior to lithification can lead to enhanced biomolecular preservation over geological time-scales. The hyperarid core of the Atacama Desert in northern Chile offers a unique environment to investigate lipid biomarker taphonomy under extreme and prolonged dryness. We investigated the accumulation and degree of preservation of lipid biomarkers in million-year-old hyperarid soils where primarily abiotic conditions influence their taphonomy. Soils were extracted and free and membrane bound lipids were analyzed across a vertical profile of 2.5 meters in the Yungay hyper-arid core of the Atacama Desert. Due to the extremely low inventory of biomass in Atacama soils, samples were collected by scientists wearing cleanroom suits to minimize anthropogenic contamination during sampling. Fatty acids were found to be well preserved in Yungay soils, and were most abundant in the clay-rich soils at approx.2 m depth (approx.750 ng of fatty acid methyl ester/g of soil). These buried clays layers were fluvially deposited approximately 2 million years ago, and have been excluded from exposure to rainwater and modern surficial processes since their emplacement (Ewing et al., 2008). Monocarboxylic fatty acid, monohydroxy fatty acid, glycerol tetraether, and n-alkane hydrocarbon content was found to change with depth. Lipid biomarker content in deeper soil layers is suggestive of soils having been formed at a time when environmental conditions were capable of supporting active microbial communities and plants. In short, total lipid extracts reveal a remarkable degree of

Value of heart-type fatty acid-binding protein (H-FABP) for ...

African Journals Online (AJOL)

Key Words: heart-type fatty acid-binding protein, acute coronary syndrome, biomarker. ... is essential to prevent major complications and death. Routinely used biomarkers such ..... fatty acid binding proteins: their function and physiological sig-.

The Significance of Microbe-Mineral-Biomarker Interactions in the Detection of Life on Mars and Beyond.

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Röling, Wilfred F M; Aerts, Joost W; Patty, C H Lucas; ten Kate, Inge Loes; Ehrenfreund, Pascale; Direito, Susana O L

2015-06-01

The detection of biomarkers plays a central role in our effort to establish whether there is, or was, life beyond Earth. In this review, we address the importance of considering mineralogy in relation to the selection of locations and biomarker detection methodologies with characteristics most promising for exploration. We review relevant mineral-biomarker and mineral-microbe interactions. The local mineralogy on a particular planet reflects its past and current environmental conditions and allows a habitability assessment by comparison with life under extreme conditions on Earth. The type of mineral significantly influences the potential abundances and types of biomarkers and microorganisms containing these biomarkers. The strong adsorptive power of some minerals aids in the preservation of biomarkers and may have been important in the origin of life. On the other hand, this strong adsorption as well as oxidizing properties of minerals can interfere with efficient extraction and detection of biomarkers. Differences in mechanisms of adsorption and in properties of minerals and biomarkers suggest that it will be difficult to design a single extraction procedure for a wide range of biomarkers. While on Mars samples can be used for direct detection of biomarkers such as nucleic acids, amino acids, and lipids, on other planetary bodies remote spectrometric detection of biosignatures has to be relied upon. The interpretation of spectral signatures of photosynthesis can also be affected by local mineralogy. We identify current gaps in our knowledge and indicate how they may be filled to improve the chances of detecting biomarkers on Mars and beyond.

Impact of coexposure on toluene biomarkers in rats.

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Cosnier, Frédéric; Nunge, Hervé; Brochard, Céline; Burgart, Manuella; Rémy, Aurélie; Décret, Marie-Josèphe; Cossec, Benoît; Campo, Pierre

2014-03-01

1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of these biomarkers may depend on factors potentially interfering with TOL biotransformation, such as the presence of other solvents in the workplace. Mercapturic acids (MAs) could be an alternative to the "traditional" TOL biomarkers. 2. This study aims (1) to investigate in rat the effects of an exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well MAs performed in these contexts compared to the traditional TOL biomarkers. 3. Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH), ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological exposure indicators were then measured. 4. Depending on the compounds in the mixture and their concentrations, TOL metabolism was accelerated (with BuOH), unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an increase in blood TOL concentrations, even at authorized atmospheric concentrations, which may potentiate the effect of TOL. 5. MAs excretions are little affected by coexposure scenarios, their levels correlating well with atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric TOL exposure.

Evaluation of Tetrahydrobiopterin Therapy with Large Neutral Amino Acid Supplementation in Phenylketonuria: Effects on Potential Peripheral Biomarkers, Melatonin and Dopamine, for Brain Monoamine Neurotransmitters.

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Shoji Yano

Full Text Available Phenylketonuria (PKU is due to a defective hepatic enzyme, phenylalanine (Phe hydroxylase. Transport of the precursor amino acids from blood into the brain for serotonin and dopamine synthesis is reported to be inhibited by high blood Phe concentrations. Deficiencies of serotonin and dopamine are involved in neurocognitive dysfunction in PKU.(1 To evaluate the effects of sapropterin (BH4 and concurrent use of large neutral amino acids (LNAA on the peripheral biomarkers, melatonin and dopamine with the hypothesis they reflect brain serotonin and dopamine metabolism. (2 To evaluate synergistic effects with BH4 and LNAA. (3 To determine the effects of blood Phe concentrations on the peripheral biomarkers concentrations.Nine adults with PKU completed our study consisting of four 4-week phases: (1 LNAA supplementation, (2 Washout, (3 BH4 therapy, and (4 LNAA with BH4 therapy. An overnight protocol measured plasma amino acids, serum melatonin, and 6-sulfatoxymelatonin and dopamine in first void urine after each phase.(1 Three out of nine subjects responded to BH4. A significant increase of serum melatonin levels was observed in BH4 responders with decreased blood Phe concentration. No significant change in melatonin, dopamine or Phe levels was observed with BH4 in the subjects as a whole. (2 Synergistic effects with BH4 and LNAA were observed in serum melatonin in BH4 responders. (3 The relationship between serum melatonin and Phe showed a significant negative slope (p = 0.0005 with a trend toward differing slopes among individual subjects (p = 0.066. There was also a negative association overall between blood Phe and urine 6-sulfatoxymelatonin and dopamine (P = 0.040 and 0.047.Blood Phe concentrations affected peripheral monoamine neurotransmitter biomarker concentrations differently in each individual with PKU. Melatonin levels increased with BH4 therapy only when blood Phe decreased. Monitoring peripheral neurotransmitter metabolites may assist in

Untargeted mass spectrometry-based metabolomic profiling of pleural effusions: fatty acids as novel cancer biomarkers for malignant pleural effusions.

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Lam, Ching-Wan; Law, Chun-Yiu

2014-09-05

Untargeted mass spectrometry-based metabolomic profiling is a powerful analytical method used for broad-spectrum identification and quantification of metabolites in biofluids in human health and disease states. In this study, we exploit metabolomic profiling for cancer biomarker discovery for diagnosis of malignant pleural effusions. We envisage the result will be clinically useful since currently there are no cancer biomarkers that are accurate enough for the diagnosis of malignant pleural effusions. Metabolomes of 32 malignant pleural effusions from lung cancer patients and 18 benign effusions from patients with pulmonary tuberculosis were analyzed using reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) using AB SCIEX TripleTOF 5600. MS spectra were analyzed using XCMS, PeakView, and LipidView. Metabolome-Wide Association Study (MWAS) was performed by Receiver Operating Characteristic Curve Explorer and Tester (ROCCET). Insignificant markers were filtered out using a metabolome-wide significance level (MWSL) with p-value pleural effusions. Using a ratio of FFA 18:1-to-ceramide (d18:1/16:0), the area-under-ROC was further increased to 0.99 (95% CI = 0.91-1.00) with sensitivity 93.8% and specificity 100.0%. Using untargeted metabolomic profiling, the diagnostic cancer biomarker with the largest area-under-ROC can be determined objectively. This lipogenic phenotype could be explained by overexpression of fatty acid synthase (FASN) in cancer cells. The diagnostic performance of FFA 18:1-to-ceramide (d18:1/16:0) ratio supports its use for diagnosis of malignant pleural effusions.

Hepatic inflammatory biomarkers and its link with obesity and chronic diseases.

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Pinheiro Volp, Ana Carolina; Santos Silva, Fernanda Cacilda; Bressan, Josefina

2015-05-01

The low-grade inflammation and insulin resistance are two events that could be present in varying degrees, on obesity and chronic diseases. The degree of subclinical inflammation can be gauged by measuring the concentrations of some inflammatory biomarkers, including the hepatic origin ones. Some of those biomarkers are sialic acid, α1-antitrypsin and the C-terminal fragment of alpha1-antitrypsin, ceruloplasmin, fibrinogen, haptoglobin, homocystein and plasminogen activator inhibitor-1. To approach the relation between adiposity and hepatic inflammatory markers, and to assess the possible associations between hepatic inflammatory biomarkers and obesity, as well as their capacity of predicting chronic diseases such as type 2 diabetes and atherotrombotic cardiovascular diseases. We used electronic scientific databases to select articles without restricting publication year. The sialic acid predicts the chance increase to become type 2 diabetic independently of BMI. Moreover, the α1-antitripsin, ceruloplasmin, fibrinogen and haptoglobulin biomarkers, seem predict the chance increase to become type 2 diabetic, dependently, of BMI. So, this process could be aggravated by obesity. The concentrations of fibrinogen, homocystein and PAI-1 increase proportionally to insulin resistance, showing its relation with metabolic syndrome (insulin resistance state) and with type 2 diabetes. In relation to cardiovascular diseases, every biomarkers reported in this review seem to increase the risk, becoming useful in add important prognostic. This review integrates the knowledge concerning the possible interactions of inflammatory mediators, in isolation or in conjunction, with obesity and chronic diseases, since these biomarkers play different functions and follow diverse biochemical routes in human body metabolism. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Development of fatty acid biomarkers for the identification of wild and aquacultured sea cucumber ( Apostichopus japonicus)

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Zadorozhnyj, P. A.; Pivnenko, T. N.; Kovalev, N. N.

2016-02-01

In this study, the fatty acids (FAs) of the organs and tissues of sea cucumber ( Apostichopus japonicus) were profiled in order to compare the FA composition of sea cucumber collected from natural habitat (wild) and cages (cultured). The differences in FA contents in dermomuscular tube, peripharyngeal annulus, gonad and intestine (with or without content) between the wild and the cultured were determined. The main fatty acids in all organs and tissues were 20:5n-3, 16:1n-7, 20:4n-6, 22:6n-3, 18:0, and 18:1n-7. The basically different FAs of body wall and digestive tube were 16:1n-7, 18:1n-9 and 20:1n-11. The ratio of saturated to mono- and polyunsaturated FAs in digestive tube was independent on inside content while there was a redistribution of the total amount of n-3 and n-6 fatty acids. The comparison of FA composition of the wild and the cultured sea cucumber showed that 20:5n-3, 16:1n-7 and 18:1n-7 predominated the wild while 20:4n-6 predominated the cultured. The content of branched-chain fatty acids in the wild was 3%-4% and about 9% in the cultured. The possible FAs for identifying the wild and the cultured sea cucumbers were selected. It was suggested that the indexes such as the ratio of either (n-3:n-6) to (n-7:n-6) or (n-3) + (n-7) to (n-6) may serve as the biomarkers distinguishing the wild and the cultured sea cucumber.

Multicollinearity may lead to artificial interaction: an example from a cross sectional study of biomarkers.

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Sithisarankul, P; Weaver, V M; Diener-West, M; Strickland, P T

1997-06-01

Collinearity is the situation which arises in multiple regression when some or all of the explanatory variables are so highly correlated with one another that it becomes very difficult, if not impossible, to disentangle their influences and obtain a reasonably precise estimate of their effects. Suppressor variable is one of the extreme situations of collinearity that one variable can substantially increase the multiple correlation when combined with a variable that is only modestly correlated with the response variable. In this study, we describe the process by which we disentangled and discovered multicollinearity and its consequences, namely artificial interaction, using the data from cross-sectional quantification of several biomarkers. We showed how the collinearity between one biomarker (blood lead level) and another (urinary trans, trans-muconic acid) and their interaction (blood lead level* urinary trans, trans-muconic acid) can lead to the observed artificial interaction on the third biomarker (urinary 5-aminolevulinic acid).

Biomarkers of acute kidney injury in neonatal encephalopathy.

LENUS (Irish Health Repository)

Sweetman, D U

2013-03-01

Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

Comparison of Glycomacropeptide with Phenylalanine Free-Synthetic Amino Acids in Test Meals to PKU Patients: No Significant Differences in Biomarkers, Including Plasma Phe Levels

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Kirsten K. Ahring

2018-01-01

Full Text Available Introduction. Management of phenylketonuria (PKU is achieved through low-phenylalanine (Phe diet, supplemented with low-protein food and mixture of free-synthetic (FS amino acid (AA. Casein glycomacropeptide (CGMP is a natural peptide released in whey during cheese-making and does not contain Phe. Lacprodan® CGMP-20 used in this study contained a small amount of Phe due to minor presence of other proteins/peptides. Objective. The purpose of this study was to compare absorption of CGMP-20 to FSAA with the aim of evaluating short-term effects on plasma AAs as well as biomarkers related to food intake. Methods. This study included 8 patients, who had four visits and tested four drink mixtures (DM1–4, consisting of CGMP, FSAA, or a combination. Plasma blood samples were collected at baseline, 15, 30, 60, 120, and 240 minutes (min after the meal. AA profiles and ghrelin were determined 6 times, while surrogate biomarkers were determined at baseline and 240 min. A visual analogue scale (VAS was used for evaluation of taste and satiety. Results. The surrogate biomarker concentrations and VAS scores for satiety and taste were nonsignificant between the four DMs, and there were only few significant results for AA profiles (not Phe. Conclusion. CGMP and FSAA had the overall same nonsignificant short-term effect on biomarkers, including Phe. This combination of FSAA and CGMP is a suitable supplement for PKU patients.

Prostate cancer biomarker profiles in urinary sediments and exosomes

NARCIS (Netherlands)

Dijkstra, Siebren; Birker, Ingrid L.; Smit, Frank P.; Leyten, Gisele H. J. M.; de Reijke, Theo M.; van Oort, Inge M.; Mulders, Peter F. A.; Jannink, Sander A.; Schalken, Jack A.

2014-01-01

Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before urine

Prostate cancer biomarker profiles in urinary sediments and exosomes

NARCIS (Netherlands)

Dijkstra, S.; Birker, I.L.; Smit, F.P.; Leyten, G.H.J.M.; Reijke, T.M. de; Oort, I.M. van; Mulders, P.F.A.; Jannink, S.A.; Schalken, J.A.

2014-01-01

PURPOSE: Urinary biomarker tests for diagnosing prostate cancer have gained considerable interest. Urine is a complex mixture that can be subfractionated. We evaluated 2 urinary fractions that contain nucleic acids, ie cell pellets and exosomes. The influence of digital rectal examination before

Organic matter diagenesis within the water column and surface sediments of the northern Sargasso Sea revealed by lipid biomarkers

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Conte, M. H.; Pedrosa Pàmies, R.; Weber, J.

2017-12-01

The intensity of particle cycling processes within the mesopelagic and bathypelagic ocean controls the length scale of organic material (OM) remineralization and diagenetic transformations of OM composition through the water column and into the sediments. To elucidate the OM cycling in the oligotrophic North Atlantic gyre, we analyzed lipid biomarkers in the suspended particles (30-4400 m depth, 100 mab), the particle flux (500 m, 1500 m and 3200 m depth), and in the underlying surficial sediments (0-0.5 cm, 4500-4600 m depth) collected at the Oceanic Flux Program (OFP) time series site located 75km SE of Bermuda. Changes in lipid biomarker concentration and composition with depth highlight the rapid remineralization of OM within the upper mesopelagic layer and continuing diagenetic transformations of OM throughout the water column and within surficial sediments. Despite observed similarities in biomarker composition in suspended and sinking particles, results show there are also consistent differences in relative contributions of phytoplankton-, bacterial- and zooplankton-derived sources that are maintained throughout the water column. For example, sinking particles are more depleted in labile biomarkers (e.g. polyunsaturated fatty acids (PUFA)) and more enriched in bacteria-derived biomarkers (e.g. hopanoids and odd/branched fatty acids) and indicators of fecal-derived OM (e.g. saturated fatty acids, FA 18:1w9 and cholesterol) than in the suspended pool. Strong seasonality in deep (3200 m) fluxes of phytoplankton-derived biomarkers reflect the seasonal input of bloom-derived material to underlying sediments. The rapid diagenetic alteration of this bloom-derived input is evidenced by depletion of PUFAs and enrichment of microbial biomarkers (e.g. odd/branched fatty acids) in surficial sediments over a two month period.

Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers

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Zhuoling An

2018-01-01

Full Text Available Metabolic pathway disturbances associated with drug-induced liver injury remain unsatisfactorily characterized. Diagnostic biomarkers for hepatotoxicity have been used to minimize drug-induced liver injury and to increase the clinical safety. A metabolomics strategy using rapid-resolution liquid chromatography/tandem mass spectrometry (RRLC-MS/MS analyses and multivariate statistics was implemented to identify potential biomarkers for hydrazine-induced hepatotoxicity. The global serum and urine metabolomics of 30 hydrazine-treated rats at 24 or 48 h postdosing and 24 healthy rats were characterized by a metabolomics approach. Multivariate statistical data analyses and receiver operating characteristic (ROC curves were performed to identify the most significantly altered metabolites. The 16 most significant potential biomarkers were identified to be closely related to hydrazine-induced liver injury. The combination of these biomarkers had an area under the curve (AUC > 0.85, with 100% specificity and sensitivity, respectively. This high-quality classification group included amino acids and their derivatives, glutathione metabolites, vitamins, fatty acids, intermediates of pyrimidine metabolism, and lipids. Additionally, metabolomics pathway analyses confirmed that phenylalanine, tyrosine, and tryptophan biosynthesis as well as tyrosine metabolism had great interactions with hydrazine-induced liver injury in rats. These discriminating metabolites might be useful in understanding the pathogenesis mechanisms of liver injury and provide good prospects for drug-induced liver injury diagnosis clinically.

Proteomic Analysis of Plasma from California Sea Lions (Zalophus californianus Reveals Apolipoprotein E as a Candidate Biomarker of Chronic Domoic Acid Toxicosis.

Directory of Open Access Journals (Sweden)

Benjamin A Neely

Full Text Available Domoic acid toxicosis (DAT in California sea lions (Zalophus californianus is caused by exposure to the marine biotoxin domoic acid and has been linked to massive stranding events and mortality. Diagnosis is based on clinical signs in addition to the presence of domoic acid in body fluids. Chronic DAT further is characterized by reoccurring seizures progressing to status epilepticus. Diagnosis of chronic DAT is often slow and problematic, and minimally invasive tests for DAT have been the focus of numerous recent biomarker studies. The goal of this study was to retrospectively profile plasma proteins in a population of sea lions with chronic DAT and those without DAT using two dimensional gel electrophoresis to discover whether individual, multiple, or combinations of protein and clinical data could be utilized to identify sea lions with DAT. Using a training set of 32 sea lion sera, 20 proteins and their isoforms were identified that were significantly different between the two groups (p<0.05. Interestingly, 11 apolipoprotein E (ApoE charge forms were decreased in DAT samples, indicating that ApoE charge form distributions may be important in the progression of DAT. In order to develop a classifier of chronic DAT, an independent blinded test set of 20 sea lions, seven with chronic DAT, was used to validate models utilizing ApoE charge forms and eosinophil counts. The resulting support vector machine had high sensitivity (85.7% with 92.3% negative predictive value and high specificity (92.3% with 85.7% positive predictive value. These results suggest that ApoE and eosinophil counts along with machine learning can perform as a robust and accurate tool to diagnose chronic DAT. Although this analysis is specifically focused on blood biomarkers and routine clinical data, the results demonstrate promise for future studies combining additional variables in multidimensional space to create robust classifiers.

Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

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Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

2014-09-05

Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury.

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Kane-Gill, Sandra L; Smithburger, Pamela L; Kashani, Kianoush; Kellum, John A; Frazee, Erin

2017-11-01

Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N-acetyl-β-D-glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.

Molecular Elucidation of Disease Biomarkers at the Interface of Chemistry and Biology.

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Zhang, Liqin; Wan, Shuo; Jiang, Ying; Wang, Yanyue; Fu, Ting; Liu, Qiaoling; Cao, Zhijuan; Qiu, Liping; Tan, Weihong

2017-02-22

Disease-related biomarkers are objectively measurable molecular signatures of physiological status that can serve as disease indicators or drug targets in clinical diagnosis and therapy, thus acting as a tool in support of personalized medicine. For example, the prostate-specific antigen (PSA) biomarker is now widely used to screen patients for prostate cancer. However, few such biomarkers are currently available, and the process of biomarker identification and validation is prolonged and complicated by inefficient methods of discovery and few reliable analytical platforms. Therefore, in this Perspective, we look at the advanced chemistry of aptamer molecules and their significant role as molecular probes in biomarker studies. As a special class of functional nucleic acids evolved from an iterative technology termed Systematic Evolution of Ligands by Exponential Enrichment (SELEX), these single-stranded oligonucleotides can recognize their respective targets with selectivity and affinity comparable to those of protein antibodies. Because of their fast turnaround time and exceptional chemical properties, aptamer probes can serve as novel molecular tools for biomarker investigations, particularly in assisting identification of new disease-related biomarkers. More importantly, aptamers are able to recognize biomarkers from complex biological environments such as blood serum and cell surfaces, which can provide direct evidence for further clinical applications. This Perspective highlights several major advancements of aptamer-based biomarker discovery strategies and their potential contribution to the practice of precision medicine.

Intestinal Integrity Biomarkers in Early Antiretroviral-Treated Perinatally HIV-1-Infected Infants.

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Koay, Wei Li A; Lindsey, Jane C; Uprety, Priyanka; Bwakura-Dangarembizi, Mutsa; Weinberg, Adriana; Levin, Myron J; Persaud, Deborah

2018-05-12

Biomarkers of intestinal integrity (intestinal fatty acid binding protein (iFABP) and zonulin), were compared in early antiretroviral-treated, HIV-1-infected (HIV+; n=56) African infants and HIV-exposed but uninfected (HEU; n=53) controls. Despite heightened inflammation and immune activation in HIV+ infants, iFABP and zonulin levels at three months of age were not different from those in HEU infants, and largely not correlated with inflammatory and immune activation biomarkers. However, zonulin levels increased, and became significantly higher in HIV+ compared to HEU infants by five months of age despite ART-suppression. These findings have implications for intestinal integrity biomarker profiling in perinatal HIV-1 infection.

Lipid Biomarkers and Molecular Carbon Isotopes for Elucidating Carbon Cycling Pathways in Hydrothermal Vents

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Zhang, C. L.; Dai, J.; Campbell, B.; Cary, C.; Sun, M.

2003-12-01

Increasing molecular evidence suggests that hydrothermal vents in mid-ocean ridges harbor large populations of free-living bacteria, particularly the epsilon Proteobacteria. However, pathways for carbon metabolism by these bacteria are poorly known. We are addressing this question by analyzing the lipid biomarkers and their isotope signatures in environments where the epsilon Proteobacteria are likely predominant. Solid materials were collected from hydrothermal vents in the East Pacific Rise and at the Guaymas Basin in the Gulf of California. Fatty acids extracted from these samples are dominated by 16:0 (27-41%), 18:0 (16-48%), 18:1 (11-42%), 16:1 (7-12%), and 14:0 (5-28%). In addition, 15:0 and anteiso-15:0 are significantly present (2-3%) in samples from the Guaymas Basin. The isotopic compositions of these fatty acids range from -15.0\\permil to -33.1\\permil with the most positive values occurring only in monounsaturated fatty acids (16:1 and 18:1). We are currently unable to assign these biomarkers to any of the epsilon Proteobacteria because biomarkers are poorly known for these organisms isolated from the vents. However, no polyunsaturated fatty acids were detected in these samples, which are consistent with the absence of vent animals at the sampling sites. Signature biomarkers of 20:1 and cy21:0, which are characteristic of the thermophilic chemolithoautotrophs such as Aquificales, are also absent in these samples. These results imply that the deeply branched Aquificales species do not constitute the major microbial community in these vent environments. The large range of molecular isotopic compositions suggests that these lipids are synthesized from various carbon sources with different isotopic compositions or through different biosynthetic pathways, or both. We are currently measuring the isotopic compositions of the total organic carbon in the bulk samples and will determine the fractionations between lipid biomarkers and the total organic carbon

Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

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Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

2016-10-01

We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

Biomarkers of Habitual Fish Intake in Adipose-Tissue

DEFF Research Database (Denmark)

Marckmann, P.; Lassen, Anne Dahl; Haraldsdottir, H.

1995-01-01

The association between habitual fish and marine n-3 polyunsaturated fatty acid (PUFA) intake, and the fatty acid composition of subcutaneous fat was studied in 24 healthy young volunteers. Habitual dietary intakes were estimated from three 7-d weighed food records made at months 0, 5, and 8...... of the 8-mo study period. The adipose tissue fatty acid composition of each individual was determined by gas chromatography as the mean of two gluteal biopsies, obtained in the first and the last month of the study. The daily consumption of fish and of marine n-3 PUFAs in absolute terms (g....../d) was significantly associated with adipose tissue docosahexaenoic acid content (DHA; r = 0.55 and 0.58, respectively, P acid contents. Our study indicates that the adipose tissue DHA content is the biomarker of choice for the assessment of long...

Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials

International Nuclear Information System (INIS)

Richter, Merle K.; Focks, Andreas; Siegfried, Barbara; Rentsch, Daniel; Krauss, Martin; Schwarzenbach, René P.; Hollender, Juliane

2013-01-01

The effects of sulfathiazole (STA) on Escherichia coli with glucose as a growth substrate was investigated to elucidate the effect-based reaction of sulfonamides in bacteria and to identify biomarkers for bacterial uptake and effect. The predominant metabolite was identified as pterine-sulfathiazole by LC-high resolution mass spectrometry. The formation of pterine-sulfathiazole per cell was constant and independent of the extracellular STA concentrations, as they exceeded the modeled half-saturation concentration K M S of 0.011 μmol L −1 . The concentration of the dihydrofolic acid precursor para-aminobenzoic acid (pABA) increased with growth and with concentrations of the competitor STA. This increase was counteracted for higher STA concentrations by growth inhibition as verified by model simulation of pABA dynamics. The EC value for the inhibition of pABA increase was 6.9 ± 0.7 μmol L −1 STA, which is similar to that calculated from optical density dynamics indicating that pABA is a direct biomarker for the SA effect. - Highlights: ► Elucidation of the effect-based reaction of sulfonamides in bacteria. ► Identification of a biomarker for uptake and effect-based reaction of sulfonamides. ► Investigation of a biomarker for the bacterial growth inhibition by sulfonamides. ► Quantitative mechanistic modeling of biomarker dynamics using enzyme kinetics. ► Mechanistic quantitative linking of sulfonamide concentrations and effects. - Identification of specific biomarkers for the uptake and effect-based reaction of sulfonamides in bacteria and resulting growth inhibition.

Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer.

Science.gov (United States)

Nedaeinia, R; Manian, M; Jazayeri, M H; Ranjbar, M; Salehi, R; Sharifi, M; Mohaghegh, F; Goli, M; Jahednia, S H; Avan, A; Ghayour-Mobarhan, M

2017-02-01

The most important biological function of exosomes is their possible use as biomarkers in clinical diagnosis. Compared with biomarkers identified in conventional specimens such as serum or urine, exosomal biomarkers provide the highest amount of sensitivity and specificity, which can be attributed to their excellent stability. Exosomes, which harbor different types of proteins, nucleic acids and lipids, are present in almost all bodily fluids. The molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), are promising as biomarkers in clinical diagnosis. This discovery that exosomes also contain messenger RNAs and miRNAs shows that they could be carriers of genetic information. Although the majority of RNAs found in exosomes are degraded RNA fragments with a length of exosomal miRNAs have been found to be associated with certain diseases. Several studies have pointed out miRNA contents of circulating exosomes that are similar to those of originating cancer cells. In this review, the recent advances in circulating exosomal miRNAs as biomarkers in gastrointestinal cancers are discussed. These studies indicated that miRNAs can be detected in exosomes isolated from body fluids such as saliva, which suggests potential advantages of using exosomal miRNAs as noninvasive novel biomarkers.

Neuronal damage biomarkers in the identification of patients at risk of long-term postoperative cognitive dysfunction after cardiac surgery

NARCIS (Netherlands)

Kok, W F; Koerts, Janneke; Tucha, O; Scheeren, T W L; Absalom, A R

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein β, as well as plasma-free

Accumulation of 24S-hydroxycholesterol in neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0): argument in favor of 24S-hydroxycholesterol as a potential biomarker of neurolipotoxicity.

Science.gov (United States)

Zarrouk, A; Hammami, M; Moreau, T; Lizard, G

2015-02-01

Cholesterol oxide derivatives (oxysterols) are viewed as potential biomarkers of neurodegenerative diseases. 24S-hydroxycholesterol, an oxysterol produced only in brain neurons, is often found for unknown reasons in increased levels in the plasma in patients with neurodegenerative diseases. On human neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0) identified at increased levels in the tissues and plasma of patients with peroxisomal leukodystrophies and Alzheimer's disease, we observed increased level of 24S-hydroxycholesterol associated with C26:0 induced lipotoxicity. This finding reinforces the hypothesis suggesting that 24S-hydroxycholesterol could constitute a biomarker of neurotoxicity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine.

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Eckersall, P D; Bell, R

2010-07-01

Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and alpha(1) acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease. Copyright 2010 Elsevier Ltd. All rights reserved.

Pharmacogenomic Biomarkers

Directory of Open Access Journals (Sweden)

Sandra C. Kirkwood

2002-01-01

Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

Deciphering metabonomics biomarkers-targets interactions for psoriasis vulgaris by network pharmacology.

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Gu, Jiangyong; Li, Li; Wang, Dongmei; Zhu, Wei; Han, Ling; Zhao, Ruizhi; Xu, Xiaojie; Lu, Chuanjian

2018-06-01

Psoriasis vulgaris is a chronic inflammatory and immune-mediated skin disease. 44 metabonomics biomarkers were identified by high-throughput liquid chromatography coupled to mass spectrometry in our previous work, but the roles of metabonomics biomarkers in the pathogenesis of psoriasis is unclear. The metabonomics biomarker-enzyme network was constructed. The key metabonomics biomarkers and enzymes were screened out by network analysis. The binding affinity between each metabonomics biomarker and target was calculated by molecular docking. A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways. Long-chain fatty acids, phospholipids, Estradiol and NADH were the most important metabonomics biomarkers. Most key enzymes belonged hydrolase, thioesterase and acyltransferase. Six proteins (TNF-alpha, MAPK3, iNOS, eNOS, COX2 and mTOR) were extensively involved in inflammatory reaction, immune response and cell proliferation, and might be drug targets for psoriasis. PI3K-Akt signaling pathway and five other pathways had close correlation with the pathogenesis of psoriasis and could deserve further research. The inflammatory reaction, immune response and cell proliferation are mainly involved in psoriasis. Network pharmacology provide a new insight into the relationships between metabonomics biomarkers and the pathogenesis of psoriasis. KEY MESSAGES   • Network pharmacology was adopted to identify key metabonomics biomarkers and enzymes.   • Six proteins were screened out as important drug targets for psoriasis.   • A binding energy-weighted polypharmacological index was introduced to evaluate the importance of target-related pathways.

Association between plasma fatty acids and inflammatory markers in patients with and without insulin resistance and in secondary prevention of cardiovascular disease, a cross-sectional study.

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Bersch-Ferreira, Ângela Cristine; Sampaio, Geni Rodrigues; Gehringer, Marcella Omena; Torres, Elizabeth Aparecida Ferraz da Silva; Ross-Fernandes, Maria Beatriz; da Silva, Jacqueline Tereza; Torreglosa, Camila Ragne; Kovacs, Cristiane; Alves, Renata; Magnoni, Carlos Daniel; Weber, Bernardete; Rogero, Marcelo Macedo

2018-02-21

Proinflammatory biomarkers levels are increased among patients with cardiovascular disease, and it is known that both the presence of insulin resistance and diet may influence those levels. However, these associations are not well studied among patients with established cardiovascular disease. Our objective is to compare inflammatory biomarker levels among cardiovascular disease secondary prevention patients with and without insulin resistance, and to evaluate if there is any association between plasma fatty acid levels and inflammatory biomarker levels among them. In this cross-sectional sub-study from the BALANCE Program Trial, we collected data from 359 patients with established cardiovascular disease. Plasma fatty acids and inflammatory biomarkers (interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, high sensitive C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor (TNF)-alpha) were measured. Biomarkers and plasma fatty acid levels of subjects across insulin resistant and not insulin resistant groups were compared, and general linear models were used to examine the association between plasma fatty acids and inflammatory biomarkers. Subjects with insulin resistance had a higher concentration of hs-CRP (p = 0.002) and IL-6 (p = 0.002) than subjects without insulin resistance. Among subjects without insulin resistance there was a positive association between stearic fatty acid and IL-6 (p = 0.032), and a negative association between alpha-linolenic fatty acid and pro-inflammatory biomarkers (p fatty acids and arachidonic fatty acid and adiponectin (p fatty acids and pro-inflammatory biomarkers (p fatty acids and adiponectin (p fatty acids. Subjects in secondary prevention for cardiovascular disease with insulin resistance have a higher concentration of hs-CRP and IL-6 than individuals without insulin resistance, and these inflammatory biomarkers are positively associated with saturated fatty acids and negatively associated with

BLOOD BIOMARKERS FOR EVALUATION OF PERINATAL ENCEPHALOPATHY

Directory of Open Access Journals (Sweden)

Ernest Marshall Graham

2016-07-01

Full Text Available Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the liquid brain biopsy. A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

Science.gov (United States)

Agréus, Lars; Kuipers, Ernst J; Kupcinskas, Limas; Malfertheiner, Peter; Di Mario, Francesco; Leja, Marcis; Mahachai, Varocha; Yaron, Niv; Van Oijen, Martijn; Perez, Guillermo Perez; Rugge, Massimo; Ronkainen, Jukka; Salaspuro, Mikko; Sipponen, Pentti; Sugano, Kentaro; Sung, Joseph

2012-01-01

Background and aims Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach. PMID:22242613

Combination of biomarkers

DEFF Research Database (Denmark)

Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

2012-01-01

The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

Salivary pH: A diagnostic biomarker.

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Baliga, Sharmila; Muglikar, Sangeeta; Kale, Rahul

2013-07-01

Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

Validation of New Cancer Biomarkers

DEFF Research Database (Denmark)

Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

2015-01-01

BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

Identification of organic acids as potential biomarkers in the urine of autistic children using gas chromatography/mass spectrometry.

Science.gov (United States)

Kałużna-Czaplińska, Joanna; Żurawicz, Ewa; Struck, Wiktoria; Markuszewski, Michał

2014-09-01

There is a need to identify metabolic phenotypes in autism as they might each require unique approaches to prevention. Biological markers can help define autism subtypes and reveal potential therapeutic targets. The aim of the study was to identify alterations of small molecular weight compounds and to find potential biomarkers. Gas chromatography/mass spectrometry was employed to evaluate major metabolic changes in low molecular weight urine metabolites of 14 children with autism spectrum disorders vs. 10 non-autistic subjects. The results prove the usefulness of an identified set of 21 endogenous compounds (including 14 organic acids), whose levels are changed in diseased children. Gas chromatography/mass spectrometry method combined with multivariate statistical analysis techniques provide an efficient way of depicting metabolic perturbations of diseases, and may potentially be applicable as a novel strategy for the noninvasive diagnosis and treatment of autism. Copyright © 2014 Elsevier B.V. All rights reserved.

Biomarkers in Autism

Directory of Open Access Journals (Sweden)

Robert eHendren

2014-08-01

Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

Measurement of Soluble Biomarkers by Flow Cytometry

OpenAIRE

Antal-Szalm?s, P?ter; Nagy, B?la; Debreceni, Ildik? Beke; Kappelmayer, J?nos

2013-01-01

Microparticle based flow cytometric assays for determination of the level of soluble biomarkers are widely used in several research applications and in some diagnostic setups. The major advantages of these multiplex systems are that they can measure a large number of analytes (up to 500) at the same time reducing assay time, costs and sample volume. Most of these assays are based on antigen-antibody interactions and work as traditional immunoassays, but nucleic acid alterations ? by using spe...

Have biomarkers made their mark? A brief review of dental biomarkers

Directory of Open Access Journals (Sweden)

Mohammed Kaleem Sultan

2014-01-01

Full Text Available Biomarkers are substances that are released into the human body by tumor cells or by other cells in response to tumor. A high level of a tumor marker is considered a sign of certain cancer, which makes biomarker the subject of many testing methods for the diagnosis of cancers. In recent times, these biomarkers have been successfully isolated to diagnose dental-related tumors, benign and malignant conditions. This article is a brief review of literature for various biomarkers used in the field of dentistry.

Screen-printed fluorescent sensors for rapid and sensitive anthrax biomarker detection

International Nuclear Information System (INIS)

Lee, Inkyu; Oh, Wan-Kyu; Jang, Jyongsik

2013-01-01

Highlights: •We fabricated flexible anthrax sensors with a simple screen-printing method. •The sensors selectively detected B. anthracis biomarker. •The sensors provide the visible alarm against anthrax attack. -- Abstract: Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide–ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax

Lipid Biomarkers for a Hypersaline Microbial Mat Community

Science.gov (United States)

Jahnke, Linda L.; Embaye, Tsege; Turk, Kendra A.

2003-01-01

The use of lipid biomarkers and their carbon isotopic compositions are valuable tools for establishing links to ancient microbial ecosystems. As witnessed by the stromatolite record, benthic microbial mats grew in shallow water lagoonal environments where microorganisms had virtually no competition apart from the harsh conditions of hypersalinity, desiccation and intense light. Today, the modern counterparts of these microbial ecosystems find appropriate niches in only a few places where extremes eliminate eukaryotic grazers. Answers to many outstanding questions about the evolution of microorganisms and their environments on early Earth are best answered through study of these extant analogs. Lipids associated with various groups of bacteria can be valuable biomarkers for identification of specific groups of microorganisms both in ancient organic-rich sedimentary rocks (geolipids) and contemporary microbial communities (membrane lipids). Use of compound specific isotope analysis adds additional refinement to the identification of biomarker source, so that it is possible to take advantage of the 3C-depletions associated with various functional groups of organisms (i.e. autotrophs, heterotrophs, methanotrophs, methanogens) responsible for the cycling of carbon within a microbial community. Our recent work has focused on a set of hypersaline evaporation ponds at Guerrero Negro, Baja California Sur, Mexico which support the abundant growth of Microcoleus-dominated microbial mats. Specific biomarkers for diatoms, cyanobacteria, archaea, green nonsulfur (GNS), sulfate reducing, and methanotrophic bacteria have been identified. Analyses of the ester-bound fatty acids indicate a highly diverse microbial community, dominated by photosynthetic organisms at the surface.

Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats.

Science.gov (United States)

Haidari, Fatemeh; Keshavarz, Seid Ali; Mohammad Shahi, Majid; Mahboob, Soltan-Ali; Rashidi, Mohammad-Reza

2011-01-01

Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases.

Identification and Quantitation of Biomarkers for Radiation-Induced Injury via Mass Spectrometry

Science.gov (United States)

Jones, Jace W.; Scott, Alison J.; Tudor, Gregory; Xu, Pu-Ting; Jackson, Isabel L.; Vujaskovic, Zeljko; Booth, Catherine; MacVittie, Thomas J.; Ernst, Robert K.; Kane, Maureen A.

2013-01-01

Biomarker identification and validation for radiation exposure is a rapidly expanding field encompassing the need for well-defined animal models and advanced analytical techniques. The resources within the consortium, Medical Countermeasures Against Radiological Threats (MCART), provide a unique opportunity for accessing well-defined animal models that simulate the key sequelae of the acute radiation syndrome and the delayed effects of acute radiation exposure. Likewise, the use of mass spectrometry-based analytical techniques for biomarker discovery and validation enables a robust analytical platform that is amenable to a variety of sample matrices and considered the benchmark for bio-molecular identification and quantitation. Herein, we demonstrate the use of two targeted mass spectrometry approaches to link established MCART animal models to identified metabolite biomarkers. Circulating citrulline concentration was correlated to gross histological gastrointestinal tissue damage and retinoic acid production in lung tissue was established to be reduced at early and late time points post high dose irradiation. Going forward, the use of mass spectrometry-based metabolomics coupled to well-defined animal models provides the unique opportunity for comprehensive biomarker discovery. PMID:24276554

Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens.

Science.gov (United States)

Tsai, Meng-Tsz; Chen, Yu-Jen; Chen, Ching-Yi; Tsai, Mong-Hsun; Han, Chia-Li; Chen, Yu-Ju; Mersmann, Harry J; Ding, Shih-Torng

2017-03-01

Background: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model. Objective: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis. Methods: Hy-Line W-36 laying hens were fed standard feed from 25 to 45 wk of age to induce fatty liver. They were killed every 4 wk, and liver and plasma were collected at each time point to assess fatty liver development and for transcriptomic and proteomic analysis. Next, selected biomarkers were confirmed in additional experiments by providing supplements of the hepatoprotective nutrients betaine [300, 600, or 900 parts per million (ppm) in vivo; 2 mM in vitro] or docosahexaenoic acid (DHA; 1% in vivo; 100 μM in vitro) to 30-wk-old Hy-Line W-36 laying hens for 4 mo and to Hy-Line W-36 chicken primary hepatocytes with oleic acid-induced steatosis. Liver or hepatocyte lipid contents and the expression of biomarkers were then examined. Results: Plasma acetoacetyl-CoA synthetase (AACS), dipeptidyl-peptidase 4 (DPP4), glutamine synthetase (GLUL), and glutathione S -transferase (GST) concentrations are well-established biomarkers for NAFLD. Selected biomarkers had significant positive associations with hepatic lipid deposition ( P steatosis accompanied by the reduced expression of selected biomarkers in vivo and in vitro ( P < 0.05). Conclusion: This study used adult laying hens to identify biomarkers for NAFLD and indicated that AACS, DPP4, GLUL, and GST could be considered to be potential diagnostic indicators for NAFLD in the future. © 2017 American Society for Nutrition.

Biomarkers as tracers for life on early earth and Mars

Science.gov (United States)

Simoneit, B. R.; Summons, R. E.; Jahnke, L. L.

1998-01-01

Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization.

Science.gov (United States)

Amur, S; LaVange, L; Zineh, I; Buckman-Garner, S; Woodcock, J

2015-07-01

The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Salivary pH: A diagnostic biomarker

Directory of Open Access Journals (Sweden)

Sharmila Baliga

2013-01-01

Full Text Available Objectives: Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. Study Design: The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. Results: The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001 whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001. Conclusion: These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.

Aptamer-based multiplexed proteomic technology for biomarker discovery.

Directory of Open Access Journals (Sweden)

Larry Gold

2010-12-01

Full Text Available The interrogation of proteomes ("proteomics" in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine.We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma. Our current assay measures 813 proteins with low limits of detection (1 pM median, 7 logs of overall dynamic range (~100 fM-1 µM, and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD. We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states.We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Aptamer-based multiplexed proteomic technology for biomarker discovery.

Science.gov (United States)

Gold, Larry; Ayers, Deborah; Bertino, Jennifer; Bock, Christopher; Bock, Ashley; Brody, Edward N; Carter, Jeff; Dalby, Andrew B; Eaton, Bruce E; Fitzwater, Tim; Flather, Dylan; Forbes, Ashley; Foreman, Trudi; Fowler, Cate; Gawande, Bharat; Goss, Meredith; Gunn, Magda; Gupta, Shashi; Halladay, Dennis; Heil, Jim; Heilig, Joe; Hicke, Brian; Husar, Gregory; Janjic, Nebojsa; Jarvis, Thale; Jennings, Susan; Katilius, Evaldas; Keeney, Tracy R; Kim, Nancy; Koch, Tad H; Kraemer, Stephan; Kroiss, Luke; Le, Ngan; Levine, Daniel; Lindsey, Wes; Lollo, Bridget; Mayfield, Wes; Mehan, Mike; Mehler, Robert; Nelson, Sally K; Nelson, Michele; Nieuwlandt, Dan; Nikrad, Malti; Ochsner, Urs; Ostroff, Rachel M; Otis, Matt; Parker, Thomas; Pietrasiewicz, Steve; Resnicow, Daniel I; Rohloff, John; Sanders, Glenn; Sattin, Sarah; Schneider, Daniel; Singer, Britta; Stanton, Martin; Sterkel, Alana; Stewart, Alex; Stratford, Suzanne; Vaught, Jonathan D; Vrkljan, Mike; Walker, Jeffrey J; Watrobka, Mike; Waugh, Sheela; Weiss, Allison; Wilcox, Sheri K; Wolfson, Alexey; Wolk, Steven K; Zhang, Chi; Zichi, Dom

2010-12-07

The interrogation of proteomes ("proteomics") in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology and medicine. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 µL of serum or plasma). Our current assay measures 813 proteins with low limits of detection (1 pM median), 7 logs of overall dynamic range (~100 fM-1 µM), and 5% median coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding signature of DNA aptamer concentrations, which is quantified on a DNA microarray. Our assay takes advantage of the dual nature of aptamers as both folded protein-binding entities with defined shapes and unique nucleotide sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to rapidly discover unique protein signatures characteristic of various disease states. We describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine.

Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

Science.gov (United States)

Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

2017-01-01

The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

Biomarkers as Proxies for Life and Environment

Science.gov (United States)

Summons, R. E.

2006-05-01

Biomarkers are organic molecules that can be used to trace specific types of organisms or biological processes in contemporary ecosystems, ancient sediments and, potentially, beyond the Earth. Biomarkers offer a means to evaluate Earth's biosphere from its earliest development to the modern day. Hydrocarbons, which are the remains of lipids that once resided in the membranes of ancestral organisms, carry chemical and isotopic clues about the nature of early ecosystems. The hydrocarbon remains of fatty acids, sterols, bacterial triterpenoids and pigments are very recalcitrant substances and can be found in rocks as old as 2.8 billion years. These molecules tell us that the three domains, archaea, bacteria and eukarya that comprise all extant life appeared quite early in Earth's history as did the oxygen-producing photosynthesis that oxidized our atmosphere and made it possible for animal life to evolve and increase in complexity. Pigment-derived biomarkers are especially useful for evaluating paleo-environmental conditions. They occur in rocks from the Archean to the present day and can be especially diagnostic for euxinic conditions. The greatest known mass extinction event occurred at the end of the Permian period and extinguished about 70% of the animals and plants that existed at that time. Much controversy surrounds its cause with many different scenarios having been proposed. An international collaboration has enabled biomarker profiles to be obtained from Permian- Triassic boundary sections in China, Australia, Canada, Tibet and Greenland. These data suggest that euxinic conditions prevailed widely in the oceans for an extended period from the Late Permian and that sulfide toxicity may have been a major factor in the demise of both plant and animal life.

Mass spectrometry for biomarker development

Energy Technology Data Exchange (ETDEWEB)

Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

2015-06-19

Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

Embroidered electrochemical sensors on gauze for rapid quantification of wound biomarkers.

Science.gov (United States)

Liu, Xiyuan; Lillehoj, Peter B

2017-12-15

Electrochemical sensors are an attractive platform for analytical measurements due to their high sensitivity, portability and fast response time. These attributes also make electrochemical sensors well suited for wearable applications which require excellent flexibility and durability. Towards this end, we have developed a robust electrochemical sensor on gauze via a unique embroidery fabrication process for quantitative measurements of wound biomarkers. For proof of principle, this biosensor was used to detect uric acid, a biomarker for wound severity and healing, in simulated wound fluid which exhibits high specificity, good linearly from 0 to 800µM, and excellent reproducibility. Continuous sensing of uric acid was also performed using this biosensor which reveals that it can generate consistent and accurate measurements for up to 7h. Experiments to evaluate the robustness of the embroidered gauze sensor demonstrate that it offers excellent resilience against mechanical stress and deformation, making it a promising wearable platform for assessing and monitoring wound status in situ. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.

Science.gov (United States)

Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F

2012-11-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples

Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

Science.gov (United States)

Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

2016-06-01

Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

Cellular fatty acid composition of marine-derived fungi

Digital Repository Service at National Institute of Oceanography (India)

PrabhaDevi; Shridhar, M.P.D.; DeSouza, L.; Naik, C.G.

. The fatty acids specific to the above mentioned fungi can be used as biomarkers for taxonomic purposes. High concentrations of C18 PUFAs (18:2 n-6 and 18:1 n-9) together with relatively high concentrations of saturated fatty acids like palmitic (16...

Identification of biomarkers for genotyping Aspergilli using non-linear methods for clustering and classification

DEFF Research Database (Denmark)

Kouskoumvekaki, Irene; Yang, Zhiyong; Jonsdottir, Svava Osk

2008-01-01

Background: In the present investigation, we have used an exhaustive metabolite profiling approach to search for biomarkers in recombinant Aspergillus nidulans (mutants that produce the 6- methyl salicylic acid polyketide molecule) for application in metabolic engineering. Results: More than 450...

Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

Energy Technology Data Exchange (ETDEWEB)

Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

2016-12-01

Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

Biomarkers of Pediatric Brain Tumors

Directory of Open Access Journals (Sweden)

Mark D Russell

2013-03-01

Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

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

International Nuclear Information System (INIS)

Moser, Virginia C.; Stewart, Nicholas; Freeborn, Danielle L.; Crooks, James; MacMillan, Denise K.; Hedge, Joan M.; Wood, Charles E.; McMahen, Rebecca L.; Strynar, Mark J.; Herr, David W.

2015-01-01

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

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

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

2015-01-15

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

Interplay of community dynamics, temperature, and productivity on the hydrogen isotope signatures of lipid biomarkers

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S. N. Ladd

2017-09-01

Full Text Available The hydrogen isotopic composition (δ2H of lipid biomarkers has diverse applications in the fields of paleoclimatology, biogeochemistry, and microbial community dynamics. Large changes in hydrogen isotope fractionation have been observed among microbes with differing core metabolisms, while environmental factors including temperature and nutrient availability can affect isotope fractionation by photoautotrophs. Much effort has gone into studying these effects under laboratory conditions with single species cultures. Moving beyond controlled environments and quantifying the natural extent of these changes in freshwater lacustrine settings and identifying their causes is essential for robust application of δ2H values of common short-chain fatty acids as a proxy of net community metabolism and of phytoplankton-specific biomarkers as a paleohydrologic proxy. This work targets the effect of community dynamics, temperature, and productivity on 2H∕1H fractionation in lipid biomarkers through a comparative time series in two central Swiss lakes: eutrophic Lake Greifen and oligotrophic Lake Lucerne. Particulate organic matter was collected from surface waters at six time points throughout the spring and summer of 2015, and δ2H values of short-chain fatty acids, as well as chlorophyll-derived phytol and the diatom biomarker brassicasterol, were measured. We paired these measurements with in situ incubations conducted with NaH13CO3, which were used to calculate the production rates of individual lipids in lake surface water. As algal productivity increased from April to June, net discrimination against 2H in Lake Greifen increased by as much as 148 ‰ for individual fatty acids. During the same time period in Lake Lucerne, net discrimination against 2H increased by as much as 58 ‰ for individual fatty acids. A large portion of this signal is likely due to a greater proportion of heterotrophically derived fatty acids in the winter and early

Acute diagnostic biomarkers for spinal cord injury: review of the literature and preliminary research report.

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Yokobori, Shoji; Zhang, Zhiqun; Moghieb, Ahmed; Mondello, Stefania; Gajavelli, Shyam; Dietrich, W Dalton; Bramlett, Helen; Hayes, Ronald L; Wang, Michael; Wang, Kevin K W; Bullock, M Ross

2015-05-01

Many efforts have been made to create new diagnostic technologies for use in the diagnosis of central nervous system injury. However, there is still no consensus for the use of biomarkers in clinical acute spinal cord injury (SCI). The aims of this review are (1) to evaluate the current status of neurochemical biomarkers and (2) to discuss their potential acute diagnostic role in SCI by reviewing the literature. PubMed (http://www.ncbi.nlm.nih.gov/pubmed) was searched up to 2012 to identify publications concerning diagnostic biomarkers in SCI. To support more knowledge, we also checked secondary references in the primarily retrieved literature. Neurofilaments, cleaved-Tau, microtubule-associated protein 2, myelin basic protein, neuron-specific enolase, S100β, and glial fibrillary acidic protein were identified as structural protein biomarkers in SCI by this review process. We could not find reports relating ubiquitin C-terminal hydrolase-L1 and α-II spectrin breakdown products, which are widely researched in other central nervous system injuries. Therefore, we present our preliminary data relating to these two biomarkers. Some of biomarkers showed promising results for SCI diagnosis and outcome prediction; however, there were unresolved issues relating to accuracy and their accessibility. Currently, there still are not many reports focused on diagnostic biomarkers in SCI. This fact warranted the need for greater efforts to innovate sensitive and reliable biomarkers for SCI. Copyright © 2015 Elsevier Inc. All rights reserved.

Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

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Boutin, Michel; Auray-Blais, Christiane

2015-03-01

Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

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Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2017-08-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

SERS-based inverse molecular sentinel (iMS) nanoprobes for multiplexed detection of microRNA cancer biomarkers in biological samples

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Crawford, Bridget M.; Wang, Hsin-Neng; Fales, Andrew M.; Bowie, Michelle L.; Seewaldt, Victoria L.; Vo-Dinh, Tuan

2017-02-01

The development of sensitive and selective biosensing techniques is of great interest for clinical diagnostics. Here, we describe the development and application of a surface enhanced Raman scattering (SERS) sensing technology, referred to as "inverse Molecular Sentinel (iMS)" nanoprobes, for the detection of nucleic acid biomarkers in biological samples. This iMS nanoprobe involves the use of plasmonic-active nanostars as the sensing platform for a homogenous assay for multiplexed detection of nucleic acid biomarkers, including DNA, RNA and microRNA (miRNA). The "OFF-to-ON" signal switch is based on a non-enzymatic strand-displacement process and the conformational change of stem-loop (hairpin) oligonucleotide probes upon target binding. Here, we demonstrate the development of iMS nanoprobes for the detection of DNA sequences as well as a modified design of the nanoprobe for the detection of short (22-nt) microRNA sequences. The application of iMS nanoprobes to detect miRNAs in real biological samples was performed with total small RNA extracted from breast cancer cell lines. The multiplex capability of the iMS technique was demonstrated using a mixture of the two differently labeled nanoprobes to detect miR-21 and miR-34a miRNA biomarkers for breast cancer. The results of this study demonstrate the feasibility of applying the iMS technique for multiplexed detection of nucleic acid biomarkers, including short miRNAs molecules.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

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Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

Relationship between Investigative Biomarkers and Radiographic Grading in Patients with Knee Osteoarthritis

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Anitua, Eduardo; Sánchez, Mikel; de la Fuente, Maria; Azofra, Juan; Zalduendo, Mar; Aguirre, Jose J.; Andía, Isabel

2009-01-01

Objective. To examine new investigative biomarkers and their relevance for radiographic severity in knee osteoarthritis. Methods. The group comprised 63 patients with 73 knees examined. Patients were divided according to radiographic severity to allow for comparison of biomarker levels. Hyaluronic acid (HA), matrix metalloproteases (MMP-1, MMP-3 and MMP-13), tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2), platelet-derived growth factor (PDGF-AB), transformed growth factor (TGF-β), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and insulin-like growth factor (IGF-I) were measured on synovial fluid and in plasma releasate at a single time point. Principal component analysis (PCA) followed by analysis of covariance were applied to evaluate data. Results. Four different groups of biomarker were identified in plasma releasates. The first (platelet number, PDGF-AB and TGF-β) and second groups (HA and IGF-I) were related to radiographic severity, P = .005 and P = .022, respectively. The third (MMP-1 and TIMP-2) and fourth groups (MMP-3 and TIMP-1) represented the catabolic balance, but were not associated to radiographic grading. Three different clusters of biomarkers were found in synovial fluid but did not show any significant association to radiographic grading. Conclusions. New imaging approaches to assess structural deterioration and correlation with biomarker levels are warranted to advance in OA research. PMID:20130801

Relationship between Investigative Biomarkers and Radiographic Grading in Patients with Knee Osteoarthritis

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Eduardo Anitua

2009-01-01

Full Text Available Objective. To examine new investigative biomarkers and their relevance for radiographic severity in knee osteoarthritis. Methods. The group comprised 63 patients with 73 knees examined. Patients were divided according to radiographic severity to allow for comparison of biomarker levels. Hyaluronic acid (HA, matrix metalloproteases (MMP-1, MMP-3 and MMP-13, tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2, platelet-derived growth factor (PDGF-AB, transformed growth factor (TGF-β, vascular endothelial growth factor (VEGF, hepatocyte growth factor (HGF and insulin-like growth factor (IGF-I were measured on synovial fluid and in plasma releasate at a single time point. Principal component analysis (PCA followed by analysis of covariance were applied to evaluate data. Results. Four different groups of biomarker were identified in plasma releasates. The first (platelet number, PDGF-AB and TGF-β and second groups (HA and IGF-I were related to radiographic severity, P=.005 and P=.022, respectively. The third (MMP-1 and TIMP-2 and fourth groups (MMP-3 and TIMP-1 represented the catabolic balance, but were not associated to radiographic grading. Three different clusters of biomarkers were found in synovial fluid but did not show any significant association to radiographic grading. Conclusions. New imaging approaches to assess structural deterioration and correlation with biomarker levels are warranted to advance in OA research.

An in vitro metabolomics approach to identify hepatotoxicity biomarkers in human L02 liver cells treated with pekinenal, a natural compound.

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Shi, Jiexia; Zhou, Jing; Ma, Hongyue; Guo, Hongbo; Ni, Zuyao; Duan, Jin'ao; Tao, Weiwei; Qian, Dawei

2016-02-01

An in vitro cell metabolomics study was performed on human L02 liver cells to investigate the toxic biomarkers of pekinenal from the herb Euphorbia pekinensis Rupr. Pekinenal significantly induced L02 cell damage, which was characterised by necrosis and apoptosis. Metabolomics combined with data pattern recognition showed that pekinenal significantly altered the profiles of more than 1299 endogenous metabolites with variable importance in the projection (VIP) > 1. Further, screening correlation coefficients between the intensities of all metabolites and the extent of L02 cell damage (MTT) identified 12 biomarker hits: ten were downregulated and two were upregulated. Among these hits, LysoPC(18:1(9Z)/(11Z)), PC(22:0/15:0) and PC(20:1(11Z)/14:1(9Z)) were disordered, implying the initiation of inflammation and cell damage. Several fatty acids (FAs) (3-hydroxytetradecanedioic acid, pivaloylcarnitine and eicosapentaenoyl ethanolamide) decreased due to fatty acid oxidation. Dihydroceramide and Cer(d18:0/14:0) were also altered and are associated with apoptosis. Additional examination of the levels of intracellular reactive oxygen species (ROS) and two eicosanoids (PGE2, PGF2α) in the cell supernatant confirmed the fatty acid oxidation and arachidonic acid metabolism pathways, respectively. In summary, cell metabolomics is a highly efficient approach for identifying toxic biomarkers and helping understand toxicity mechanisms and predict herb-induced liver injury.

Soil water availability and microsite mediate fungal and bacterial phospholipid fatty acid biomarker abundances in Mojave Desert soils exposed to elevated atmospheric CO2

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Jin, V. L.; Schaeffer, S. M.; Ziegler, S. E.; Evans, R. D.

2011-06-01

Changes in the rates of nitrogen (N) cycling, microbial carbon (C) substrate use, and extracellular enzyme activities in a Mojave Desert ecosystem exposed to elevated atmospheric CO2 suggest shifts in the size and/or functional characteristics of microbial assemblages in two dominant soil microsites: plant interspaces and under the dominant shrub Larrea tridentata. We used ester-linked phospholipid fatty acid (PLFA) biomarkers as a proxy for microbial biomass to quantify spatial and temporal differences in soil microbial communities from February 2003 to May 2005. Further, we used the 13C signature of the fossil CO2 source for elevated CO2 plots to trace recent plant C inputs into soil organic matter (SOM) and broad microbial groups using δ13C (‰). Differences between individual δ13CPLFA and δ13CSOM for fungal biomarkers indicated active metabolism of newer C in elevated CO2 soils. Total PLFA-C was greater in shrub microsites compared to plant interspaces, and CO2 treatment differences within microsites increased under higher soil water availability. Total, fungal, and bacterial PLFA-C increased with decreasing soil volumetric water content (VWC) in both microsites, suggesting general adaptations to xeric desert conditions. Increases in fungal-to-bacterial PLFA-C ratio with decreasing VWC reflected functional group-specific responses to changing soil water availability. While temporal and spatial extremes in resource availability in desert ecosystems contribute to the difficulty in identifying common trends or mechanisms driving microbial responses in less extreme environments, we found that soil water availability and soil microsite interacted with elevated CO2 to shift fungal and bacterial biomarker abundances in Mojave Desert soils.

Distribution study of fatty acids (FAs) in sediments of Al-Kabeer Al-Shemali river estuary area using (HPLC) technique

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Nasser, M.; Ali, B.; Ali, A.

2010-01-01

Samples of sediments from fife sites of Al-kabeer Al-shemali river estuary area were collected during the period (22/2/2007-7/11/2007). The samples were extracted to determine their content of Fatty acids qualitatively and quantitatively by using ( HPLC) technique for determination resources of organic matter in studied sediments . The total concentrations of (FAs) varied from (0.36-1245.5μg/g dry weight).The saturated fatty acids were dominated in all samples (12.1 - 100 %) of total fatty acids. The levels of polyunsaturated fatty acids (PUFAs) were tested percent (0-18 %) of total fatty acids except one sample from surficial sediments in St 3 during 8/8/2007 .while the concentrations of monounsaturated fatty acids (MUFAs) were low (0 -21.6 %) of total fatty acids . We can use the saturated long chain fatty acid (C-22) as terrestrial biomarker. poly unsaturated fatty acid (C 1 8: 2ω6) as plankton biomarker and the Mono unsaturated fatty acid (C 1 8 : 1ω7) as bacterial biomarker.(author)

Metabolomics reveals metabolic biomarkers of Crohn's disease

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Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

2009-06-01

The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

Screening for biomarkers of liver injury induced by Polygonum multiflorum: a targeted metabolomic study

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Qin eDong

2015-10-01

Full Text Available Heshouwu (HSW, the dry roots of Polygonum multiflorum, a classical traditional Chinese medicine is used as a tonic for a wide range of conditions，particularly those associated with aging. However, it tends to be taken overdose or long term in these years, which has resulted in liver damage reported in many countries. In this study, the indicative roles of nine bile acids (BAs were evaluated to offer potential biomarkers for HSW induced liver injury. Nine BAs including cholic acid (CA and chenodeoxycholic acid (CDCA, taurocholic acid (TCA, glycocholic acid (GCA, glycochenodeoxycholic acid (GCDCA, deoxycholic acid (DCA, glycodeoxycholic acid (GDCA, ursodeoxycholic acid (UDCA and hyodeoxycholic acid (HDCA in rat bile and serum were detected by a developed LC-MS method after 42 days treatment. Partial least square-discriminate analysis (PLS-DA was applied to evaluate the indicative roles of the nine BAs, and metabolism of the nine BAs was summarized. Significant change was observed for the concentrations of nine BAs in treatment groups compared with normal control; In the PLS-DA plots of nine BAs in bile, normal control and raw HSW groups were separately clustered and could be clearly distinguished, GDCA was selected as the distinguished components for raw HSW overdose treatment group. In the PLS-DA plots of nine BAs in serum, the normal control and raw HSW overdose treatment group were separately clustered and could be clearly distinguished, and HDCA was selected as the distinguished components for raw HSW overdose treatment group. The results indicated the perturbation of nine BAs was associated with HSW induced liver injury; GDCA in bile, as well as HDCA in serum could be selected as potential biomarkers for HSW induced liver injury; it also laid the foundation for the further search on the mechanisms of liver injury induced by HSW .

Prognostic biomarkers in osteoarthritis

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Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

2013-01-01

Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

Identification of the lipid biomarkers from plasma in idiopathic pulmonary fibrosis by Lipidomics.

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Yan, Feng; Wen, Zhensong; Wang, Rui; Luo, Wenling; Du, Yufeng; Wang, Wenjun; Chen, Xianyang

2017-12-06

Idiopathic pulmonary fibrosis (IPF) is an irreversible interstitial pulmonary disease featured by high mortality, chronic and progressive course, and poor prognosis with unclear etiology. Currently, more studies have been focusing on identifying biomarkers to predict the progression of IPF, such as genes, proteins, and lipids. Lipids comprise diverse classes of molecules and play a critical role in cellular energy storage, structure, and signaling. The role of lipids in respiratory diseases, including cystic fibrosis, asthma and chronic obstructive pulmonary disease (COPD) has been investigated intensely in the recent years. The human serum lipid profiles in IPF patients however, have not been thoroughly understood and it will be very helpful if there are available molecular biomarkers, which can be used to monitor the disease progression or provide prognostic information for IPF disease. In this study, we performed the ultraperformance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) to detect the lipid variation and identify biomarker in plasma of IPF patients. The plasma were from 22 IPF patients before received treatment and 18 controls. A total of 507 individual blood lipid species were determined with lipidomics from the 40 plasma samples including 20 types of fatty acid, 159 types of glycerolipids, 221 types of glycerophospholipids, 47 types of sphingolipids, 46 types of sterol lipids, 7 types of prenol lipids, 3 types of saccharolipids, and 4 types of polyketides. By comparing the variations in the lipid metabolite levels in IPF patients, a total of 62 unique lipids were identified by statistical analysis including 24 kinds of glycerophoslipids, 30 kinds of glycerolipids, 3 kinds of sterol lipids, 4 kinds of sphingolipids and 1 kind of fatty acids. Finally, 6 out of 62 discriminating lipids were selected as the potential biomarkers, which are able to differentiate between IPF disease and controls with ROC

Biomarkers in Prostate Cancer Epidemiology

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Mudit Verma

2011-09-01

Full Text Available Understanding the etiology of a disease such as prostate cancer may help in identifying populations at high risk, timely intervention of the disease, and proper treatment. Biomarkers, along with exposure history and clinical data, are useful tools to achieve these goals. Individual risk and population incidence of prostate cancer result from the intervention of genetic susceptibility and exposure. Biochemical, epigenetic, genetic, and imaging biomarkers are used to identify people at high risk for developing prostate cancer. In cancer epidemiology, epigenetic biomarkers offer advantages over other types of biomarkers because they are expressed against a person’s genetic background and environmental exposure, and because abnormal events occur early in cancer development, which includes several epigenetic alterations in cancer cells. This article describes different biomarkers that have potential use in studying the epidemiology of prostate cancer. We also discuss the characteristics of an ideal biomarker for prostate cancer, and technologies utilized for biomarker assays. Among epigenetic biomarkers, most reports indicate GSTP1 hypermethylation as the diagnostic marker for prostate cancer; however, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS, and NSE1 also have been reported to be regulated by methylation mechanisms in prostate cancer. Current challenges in utilization of biomarkers in prostate cancer diagnosis and epidemiologic studies and potential solutions also are discussed.

Blood biomarkers of Hikikomori, a severe social withdrawal syndrome.

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Hayakawa, Kohei; Kato, Takahiro A; Watabe, Motoki; Teo, Alan R; Horikawa, Hideki; Kuwano, Nobuki; Shimokawa, Norihiro; Sato-Kasai, Mina; Kubo, Hiroaki; Ohgidani, Masahiro; Sagata, Noriaki; Toda, Hiroyuki; Tateno, Masaru; Shinfuku, Naotaka; Kishimoto, Junji; Kanba, Shigenobu

2018-02-13

Hikikomori, a severe form of social withdrawal syndrome, is a growing social issue in Japan and internationally. The pathophysiology of hikikomori has not yet been elucidated and an effective treatment remains to be established. Recently, we revealed that avoidant personality disorder is the most common comorbidity of hikikomori. Thus, we have postulated that avoidant personality is the personality underpinning hikikomori. First, we herein show relationships between avoidant personality traits, blood biomarkers, hikikomori-related psychological features, and behavioural characteristics assessed by a trust game in non-hikikomori volunteers. Avoidant personality traits were negatively associated with high-density lipoprotein cholesterol (HDL-C) and uric acid (UA) in men, and positively associated with fibrin degeneration products (FDP) and high sensitivity C-reactive protein (hsCRP) in women. Next, we recruited actual individuals with hikikomori, and compared avoidant personality traits, blood biomarkers, and psychological features between individuals with hikikomori and age-matched healthy controls. Individuals with hikikomori had higher avoidant personality scores in both sexes, and showed lower serum UA levels in men and lower HDL-C levels in women compared with healthy controls. This is the first report showing possible blood biomarkers for hikikomori, and opens the door to clarify the underlying biological pathophysiology of hikikomori.

Preliminary study on biomarkers for the fungal resistance in Vitis vinifera leaves.

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Batovska, Daniela Ilieva; Todorova, Iva Todorova; Nedelcheva, Daniela Valentinova; Parushev, Stoyan Parushev; Atanassov, Atanas Ivanov; Hvarleva, Tzvetanka Dimitrova; Djakova, Galina Jordanova; Bankova, Vassya Stefanova; Popov, Simeon Simeonov

2008-05-26

We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites--alpha- and gamma-tocopherol, squalene, alpha-amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis.

Validation of the Brazilian Healthy Eating Index-Revised Using Biomarkers in Children and Adolescents

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Roseli B. D. Toffano

2018-01-01

Full Text Available The Brazilian Healthy Eating Index-Revised (BHEI-R can be used to determine overall dietary patterns. We assessed the BHEI-R scores in children and adolescents, aged from 9 to 13 years old, and associated its component scores with biomarkers of health and dietary exposure. Three 24-h recalls were used to generate BHEI-R. Biomarkers were analyzed in plasma and red blood cells. Correlation tests, agreement, and covariance analyses were used to associate BHEI-R components with biomarkers. Data from 167 subjects were used. The strongest correlations were between fruits, vegetables and legumes with omega-6 and omega-3 fatty acids, and β-carotene intakes. Milk and dairy correlated with plasma retinol and pyridoxine. All components rich in vegetable and animal protein sources correlated with plasma creatine. Total BHEI-R scores were positively associated with intakes of omega-6, omega-3, fiber and vitamin C, and inversely associated with energy and saturated fat intakes of individuals. Plasma β-carotene and riboflavin biomarkers were positively associated with total BHEI-R. An inadequate food consumption pattern was captured by both biomarkers of health and dietary exposure. BHEI-R was validated for the above dietary components and can be associated with metabolomics and nutritional epidemiological data in future pediatric studies.

Potential serum biomarkers and metabonomic profiling of serum in ischemic stroke patients using UPLC/Q-TOF MS/MS.

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Hongxue Sun

Full Text Available Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke.Metabonomic analysis was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis was employed to study 60 patients with or without ischemic stroke (30 cases and 30 controls.Serum metabolic profiling identified a series of 12 metabolites with significant alterations, and the related metabolic pathways involved glycerophospholipid, sphingolipid, phospholipid, fat acid, acylcarnitine, heme, and purine metabolism. Subsequently, multiple logistic regression analyses of these metabolites showed uric acid, sphinganine and adrenoyl ethanolamide were potential biomarkers of ischemic stroke with an area under the receiver operating characteristic curve of 0.941.These findings provide insights into the early diagnosis and potential pathophysiology of ischemic stroke.

Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing

NARCIS (Netherlands)

Sabatté, G.S.; Feitsma, H.; Evers, T.H.; Prins, M.W.J.

2011-01-01

It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers

Associations between Specific Redox Biomarkers and Age in a Large European Cohort: The MARK-AGE Project

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Daniela Weber

2017-01-01

Full Text Available Oxidative stress and antioxidants play a role in age-related diseases and in the aging process. We here present data on protein carbonyls, 3-nitrotyrosine, malondialdehyde, and cellular and plasma antioxidants (glutathione, cysteine, ascorbic acid, uric acid, α-tocopherol, and lycopene and their relation with age in the European multicenter study MARK-AGE. To avoid confounding, only data from countries which recruited subjects from all three study groups (five of eight centers and only participants aged ≥55 years were selected resulting in data from 1559 participants. These included subjects from (1 the general population, (2 members from long-living families, and (3 their spouses. In addition, 683 middle-aged reference participants (35–54 years served as a control. After adjustment for age, BMI, smoking status, gender, and country, there were differences in protein carbonyls, malondialdehyde, 3-nitrotyrosine, α-tocopherol, cysteine, and glutathione between the 3 study groups. Protein carbonyls and 3-nitrotyrosine as well as cysteine, uric acid, and lycopene were identified as independent biomarkers with the highest correlation with age. Interestingly, from all antioxidants measured, only lycopene was lower in all aged groups and from the oxidative stress biomarkers, only 3-nitrotyrosine was increased in the descendants from long-living families compared to the middle-aged control group. We conclude that both lifestyle and genetics may be important contributors to redox biomarkers in an aging population.

Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

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Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

2017-09-18

Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

Predictive Biomarkers for Asthma Therapy.

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Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

2017-09-19

Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

Metabolomic and Genome-wide Association Studies Reveal Potential Endogenous Biomarkers for OATP1B1.

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Yee, S W; Giacomini, M M; Hsueh, C-H; Weitz, D; Liang, X; Goswami, S; Kinchen, J M; Coelho, A; Zur, A A; Mertsch, K; Brian, W; Kroetz, D L; Giacomini, K M

2016-11-01

Transporter-mediated drug-drug interactions (DDIs) are a major cause of drug toxicities. Using published genome-wide association studies (GWAS) of the human metabolome, we identified 20 metabolites associated with genetic variants in organic anion transporter, OATP1B1 (P acids and fatty acid dicarboxylates were among the metabolites discovered using both GWAS and CSA administration. In vitro studies confirmed tetradecanedioate (TDA) and hexadecanedioate (HDA) were novel substrates of OATP1B1 as well as OAT1 and OAT3. This study highlights the use of multiple datasets for the discovery of endogenous metabolites that represent potential in vivo biomarkers for transporter-mediated DDIs. Future studies are needed to determine whether these metabolites can serve as qualified biomarkers for organic anion transporters. Quantitative relationships between metabolite levels and modulation of transporters should be established. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Monitoring urinary mercapturic acids as biomarkers of human dietary exposure to acrylamide in combination with acrylamide uptake assessment based on duplicate diets.

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Ruenz, Meike; Bakuradze, Tamara; Eisenbrand, Gerhard; Richling, Elke

2016-04-01

The present human intervention study investigated the relation between the intake of acrylamide (AA) in diets with minimized, low, and high AA contents and the levels of urinary exposure biomarkers. As biomarkers, the mercapturic acids, N-acetyl-S-(carbamoylethyl)-L-cysteine (AAMA), and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA) were monitored. The study was performed with 14 healthy male volunteers over a period of 9 days, under controlled conditions excluding any inadvertent AA exposure. Dietary exposure to AA was measured by determining AA contents in duplicates of all meals consumed by the volunteers. The study design included an initial washout period of 3 days on AA-minimized diet, resulting in dietary AA exposure not exceeding 41 ng/kg bw/d. Identical washout periods of 2 days each followed the AA exposure days (day 4, low exposure, and day 7, high exposure). At the respective AA intake days, volunteers ingested 0.6-0.8 (low exposure) or 1.3-1.8 (high exposure) μg AA/kg bw/d with their food. Both low and high AA intakes resulted in an AAMA output within 72 h corresponding to 58 % of the respective AA intake. At the end of the initial 3-day washout period, an AAMA baseline level of 93 ± 31 nmol/d was recorded, suggestive for an assumed net AA baseline exposure level of 0.2-0.3 μg AA/kg bw/d.

Nutritional supplementation of hop rho iso-alpha acids, berberine, vitamin D₃, and vitamin K₁ produces a favorable bone biomarker profile supporting healthy bone metabolism in postmenopausal women with metabolic syndrome.

Science.gov (United States)

Lamb, Joseph J; Holick, Michael F; Lerman, Robert H; Konda, Veera R; Minich, Deanna M; Desai, Anuradha; Chen, Tai C; Austin, Melissa; Kornberg, Jacob; Chang, Jyh-Lurn; Hsi, Alex; Bland, Jeffrey S; Tripp, Matthew L

2011-05-01

Metabolic syndrome poses additional risk for postmenopausal women who are already at risk for osteoporosis. We hypothesized that a nutritional supplement containing anti-inflammatory phytochemicals and essential bone nutrients would produce a favorable bone biomarker profile in postmenopausal women with metabolic syndrome. In this 14-week, randomized trial, 51 women were instructed to consume a modified Mediterranean-style, low-glycemic-load diet and to engage in aerobic exercise. Those in the intervention arm (n = 25) additionally received 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D₃, and 500 μg vitamin K₁ twice daily. Forty-five women completed the study. Baseline nutrient intake did not differ between arms. Compared with baseline, the intervention arm exhibited an approximate 25% mean decrease (P vitamin D₃, and vitamin K₁ produced a more favorable bone biomarker profile indicative of healthy bone metabolism in postmenopausal women with metabolic syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiac biomarkers in Neonatology

OpenAIRE

Vijlbrief, D.C.

2015-01-01

In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

Urine stability studies for novel biomarkers of acute kidney injury.

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Parikh, Chirag R; Butrymowicz, Isabel; Yu, Angela; Chinchilli, Vernon M; Park, Meyeon; Hsu, Chi-Yuan; Reeves, W Brian; Devarajan, Prasad; Kimmel, Paul L; Siew, Edward D; Liu, Kathleen D

2014-04-01

The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers. Cross-sectional prospective. Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36). We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C. Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C. We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs). Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96). No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors. All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation

Modeling and Classification of Kinetic Patterns of Dynamic Metabolic Biomarkers in Physical Activity.

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Marc Breit

2015-08-01

Full Text Available The objectives of this work were the classification of dynamic metabolic biomarker candidates and the modeling and characterization of kinetic regulatory mechanisms in human metabolism with response to external perturbations by physical activity. Longitudinal metabolic concentration data of 47 individuals from 4 different groups were examined, obtained from a cycle ergometry cohort study. In total, 110 metabolites (within the classes of acylcarnitines, amino acids, and sugars were measured through a targeted metabolomics approach, combining tandem mass spectrometry (MS/MS with the concept of stable isotope dilution (SID for metabolite quantitation. Biomarker candidates were selected by combined analysis of maximum fold changes (MFCs in concentrations and P-values resulting from statistical hypothesis testing. Characteristic kinetic signatures were identified through a mathematical modeling approach utilizing polynomial fitting. Modeled kinetic signatures were analyzed for groups with similar behavior by applying hierarchical cluster analysis. Kinetic shape templates were characterized, defining different forms of basic kinetic response patterns, such as sustained, early, late, and other forms, that can be used for metabolite classification. Acetylcarnitine (C2, showing a late response pattern and having the highest values in MFC and statistical significance, was classified as late marker and ranked as strong predictor (MFC = 1.97, P < 0.001. In the class of amino acids, highest values were shown for alanine (MFC = 1.42, P < 0.001, classified as late marker and strong predictor. Glucose yields a delayed response pattern, similar to a hockey stick function, being classified as delayed marker and ranked as moderate predictor (MFC = 1.32, P < 0.001. These findings coincide with existing knowledge on central metabolic pathways affected in exercise physiology, such as β-oxidation of fatty acids, glycolysis, and glycogenolysis. The presented modeling

Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA clinical study.

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Richard S Finkel

Full Text Available Spinal Muscular Atrophy (SMA is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1 gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets.To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches.A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2-12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS and to a number of secondary clinical measures.A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites and 44 urine metabolites. No transcripts correlated with MHFMS.In this cross-sectional study, "BforSMA" (Biomarkers for SMA, candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with

Biomarkers of sepsis

Science.gov (United States)

2013-01-01

Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

Suitability of phytosterols alongside fatty acids as chemotaxonomic biomarkers for phytoplankton

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Sami Johan Taipale

2016-03-01

Full Text Available e composition and abundance of phytoplankton is important factor defining ecological status of marine and freshwater ecosystems. Chemotaxonomic markers (e.g., pigments and fatty acids are needed for monitoring changes in phytoplankton community and to know nutritional quality of seston for herbivorous zooplankton. Here we investigated the suitability of sterols along with fatty acids as chemotaxonomic markers by analyzing sterol and fatty acid composition of 10 different phytoplankton classes including altogether 37 strains isolated from freshwater lakes and by using multivariate statistics. We were able to detect totally 47 fatty acids and 29 sterols in our phytoplankton samples, which both differed statistically significantly between phytoplankton classes. Due to the high variation of fatty acid composition among cyanobacteria, taxonomical differentiation increased, when cyanobacteria were excluded from statistical analysis. Sterol composition was more heterogeneous within class than fatty acids and did not improve separation of phytoplankton classes when used alongside with fatty acids. However, we conclude that sterols can provide additional information on the abundance of specific genera within a class which can be generated by using fatty acids. For example, whereas high 16 ω-3 PUFAs (polyunsaturated fatty acid indicates the presence of Chlorophyceae, simultaneous high amount of ergosterol could specify the presence of Chlamydomonas spp. (Chlorophyceae. Additionally, we found specific 4α-methyl sterols for distinct Dinophyceae genus, suggesting that 4α-methyl sterols can potentially separate freshwater dinoflagellates from each other.

Suitability of Phytosterols Alongside Fatty Acids as Chemotaxonomic Biomarkers for Phytoplankton.

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Taipale, Sami J; Hiltunen, Minna; Vuorio, Kristiina; Peltomaa, Elina

2016-01-01

The composition and abundance of phytoplankton is an important factor defining ecological status of marine and freshwater ecosystems. Chemotaxonomic markers (e.g., pigments and fatty acids) are needed for monitoring changes in a phytoplankton community and to know the nutritional quality of seston for herbivorous zooplankton. Here we investigated the suitability of sterols along with fatty acids as chemotaxonomic markers using multivariate statistics, by analyzing the sterol and fatty acid composition of 10 different phytoplankton classes including altogether 37 strains isolated from freshwater lakes. We were able to detect a total of 47 fatty acids and 29 sterols in our phytoplankton samples, which both differed statistically significantly between phytoplankton classes. Due to the high variation of fatty acid composition among Cyanophyceae, taxonomical differentiation increased when Cyanophyceae were excluded from statistical analysis. Sterol composition was more heterogeneous within class than fatty acids and did not improve separation of phytoplankton classes when used alongside fatty acids. However, we conclude that sterols can provide additional information on the abundance of specific genera within a class which can be generated by using fatty acids. For example, whereas high C16 ω-3 PUFA (polyunsaturated fatty acid) indicates the presence of Chlorophyceae, a simultaneous high amount of ergosterol could specify the presence of Chlamydomonas spp. (Chlorophyceae). Additionally, we found specific 4α-methyl sterols for distinct Dinophyceae genera, suggesting that 4α-methyl sterols can potentially separate freshwater dinoflagellates from each other.

HPLC-UV Analysis Coupled with Chemometry to Identify Phenolic Biomarkers from Medicinal Plants, used as Ingredients in Two Food Supplement Formulas

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Raluca Maria Pop

2013-11-01

Full Text Available . High performance liquid chromatography (HPLC with UV detection is nowadays the reference method to identify and quantify the biomarkers of quality and authenticity of plants and food supplements. Seven medicinal plants were collected from wild flora: Taraxacum officinalis (1, Cynara scolimus (2, Silybum marianum (3, Hypericum perforatum (4,  Chelidonium majus (5, Lycopodium clavatum (6 and  Hippophae rhamnoides (7  leaves and fruits.  Two products (A and B were obtained by mixing individual plant powders. Therefore product A was obtained by mixing dandelion, artichoke and milk thistle, 1:1:1 while product B by mixing St John’s wort, Celandine and Wolf’s claw, 1:1:1. The methanolic extracts of individual plants as well as three different extracts of products A and B (using acidulated water, neutral water and acidulated methanol were analyzed using HPLC-UV for their phenolics’ fingerprint and composition. The qualitative (untargeted analysis and quantitative (targeted analysis results were further compared using Principal Component Analysis (PCA in order to identify their specific biomarkers. Thus, quantitative evaluation of individual phenolics in case of individual plants and products A and B extracts, showed specific and significant differences of composition. Both products A and B contained elagic acid as major compound. For product A, good biomarkers were trans-cinnamic, chlorogenic, caffeic and p-coumaric acids, as well silymarin and silibine originating from milk thistle. For product B, good biomarkers were quercetin and kaempherol, gallic and protocatecuic acids, this product being rich in flavonoids. In conclusion, HPLC-UV coupled with PCA analysis proved to be a rapid and useful way to identify the main biomarkers of plants’ authentication, as well of final products’ quality and safety.

Methodological utility of chemerin as a novel biomarker of immunity and metabolism

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Fabian Eichelmann

2017-07-01

Full Text Available Chemerin is a recently discovered adipokine with inflammatory and metabolic actions relevant for chronic disease development. However, evidence from human research on the role of chemerin in chronic disease risk is still lacking. We assessed the reliability of plasma chemerin concentrations measured on two occasions over a 4-month period in 207 apparently healthy participants. In addition, we explored the cross-sectional associations between chemerin and inflammatory biomarkers using Spearman partial correlation and multivariable linear regression analyses. Intra-individual reproducibility of chemerin measurements was assessed by calculating intraclass correlation coefficients (ICCs and exploration of Bland–Altman plots. Reliability analyses revealed good reproducibility of chemerin measurements (ICC: 0.72 (95%-CI 0.65, 0.78. Visual inspection of Bland–Altman plots confirmed that the two time point measurements had a high level of agreement. In correlation analyses, chemerin was positively correlated with adiposity measures (body mass index and waist circumference. In addition, independent of adiposity measures, chemerin was correlated with the biomarkers C-reactive protein, fatty acid-binding protein 4 and progranulin (Rho-s ranging from 0.23 to 0.37. In multivariable linear regression analysis, a combination of correlated factors including body mass index, waist circumference, C-reactive protein, progranulin and fatty acid-binding protein-4 explained 28.0% of chemerin concentrations. These findings demonstrate methodological utility of chemerin concentrations in population-based research setting. Human studies are highly warranted in order to provide further insights into the role of chemerin as a biomarker linking immunity and metabolism in relation to chronic disease risk.

Biomarkers of adverse drug reactions.

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Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

Analysis of Serum Metabolic Profile by Ultra-performance Liquid Chromatography-mass Spectrometry for Biomarkers Discovery: Application in a Pilot Study to Discriminate Patients with Tuberculosis

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Shuang Feng

2015-01-01

Full Text Available Background: Tuberculosis (TB is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. Metabolic signatures have been exploited in the study of several diseases. However, the serum that is successfully used in TB diagnosis on the basis of metabolic profiling is not by much. Methods: Orthogonal partial least-squares discriminant analysis was capable of distinguishing TB patients from both healthy subjects and patients with conditions other than TB. Therefore, TB-specific metabolic profiling was established. Clusters of potential biomarkers for differentiating TB active from non-TB diseases were identified using Mann-Whitney U-test. Multiple logistic regression analysis of metabolites was calculated to determine the suitable biomarker group that allows the efficient differentiation of patients with TB active from the control subjects. Results: From among 271 participants, 12 metabolites were found to contribute to the distinction between the TB active group and the control groups. These metabolites were mainly involved in the metabolic pathways of the following three biomolecules: Fatty acids, amino acids, and lipids. The receiver operating characteristic curves of 3D, 7D, and 11D-phytanic acid, behenic acid, and threoninyl-γ-glutamate exhibited excellent efficiency with area under the curve (AUC values of 0.904 (95% confidence interval [CI]: 0863-0.944, 0.93 (95% CI: 0.893-0.966, and 0.964 (95% CI: 00.941-0.988, respectively. The largest and smallest resulting AUCs were 0.964 and 0.720, indicating that these biomarkers may be involved in the disease mechanisms. The combination of lysophosphatidylcholine (18:0, behenic acid, threoninyl-γ-glutamate, and presqualene diphosphate was used to represent the most suitable biomarker group for the differentiation of patients with TB active from the control subjects, with an AUC value of 0.991. Conclusion: The

Serum Metabolite Biomarkers Discriminate Healthy Smokers from COPD Smokers

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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

Biomarker Identification Using Text Mining

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Hui Li

2012-01-01

Full Text Available Identifying molecular biomarkers has become one of the important tasks for scientists to assess the different phenotypic states of cells or organisms correlated to the genotypes of diseases from large-scale biological data. In this paper, we proposed a text-mining-based method to discover biomarkers from PubMed. First, we construct a database based on a dictionary, and then we used a finite state machine to identify the biomarkers. Our method of text mining provides a highly reliable approach to discover the biomarkers in the PubMed database.

Meeting Report--NASA Radiation Biomarker Workshop

Energy Technology Data Exchange (ETDEWEB)

Straume, Tore; Amundson, Sally A,; Blakely, William F.; Burns, Frederic J.; Chen, Allen; Dainiak, Nicholas; Franklin, Stephen; Leary, Julie A.; Loftus, David J.; Morgan, William F.; Pellmar, Terry C.; Stolc, Viktor; Turteltaub, Kenneth W.; Vaughan, Andrew T.; Vijayakumar, Srinivasan; Wyrobek, Andrew J.

2008-05-01

A summary is provided of presentations and discussions from the NASA Radiation Biomarker Workshop held September 27-28, 2007, at NASA Ames Research Center in Mountain View, California. Invited speakers were distinguished scientists representing key sectors of the radiation research community. Speakers addressed recent developments in the biomarker and biotechnology fields that may provide new opportunities for health-related assessment of radiation-exposed individuals, including for long-duration space travel. Topics discussed include the space radiation environment, biomarkers of radiation sensitivity and individual susceptibility, molecular signatures of low-dose responses, multivariate analysis of gene expression, biomarkers in biodefense, biomarkers in radiation oncology, biomarkers and triage following large-scale radiological incidents, integrated and multiple biomarker approaches, advances in whole-genome tiling arrays, advances in mass-spectrometry proteomics, radiation biodosimetry for estimation of cancer risk in a rat skin model, and confounding factors. Summary conclusions are provided at the end of the report.

The use of plant-specific pyrolysis products as biomarkers in peat deposits

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Schellekens, Judith; Bradley, Jonathan A.; Kuyper, Thomas W.; Fraga, Isabel; Pontevedra-Pombal, Xabier; Vidal-Torrado, Pablo; Abbott, Geoffrey D.; Buurman, Peter

2015-09-01

Peatlands are archives of environmental change that can be driven by climate and human activity. Proxies for peatland vegetation composition provide records of (local) environmental conditions that can be linked to both autogenic and allogenic factors. Analytical pyrolysis offers a molecular fingerprint of peat, and thereby a suite of environmental proxies. Here we investigate analytical pyrolysis as a method for biomarker analysis. Pyrolysates of 48 peatland plant species were compared, comprising seventeen lichens, three Sphagnum species, four non-Sphagnum mosses, eleven graminoids (Cyperaceae, Juncaceae, Poaceae), five Ericaceae and six species from other families. This resulted in twenty-one potential biomarkers, including new markers for lichens (3-methoxy-5-methylphenol) and graminoids (ferulic acid methyl ester). The potential of the identified biomarkers to reconstruct vegetation composition is discussed according to their depth records in cores from six peatlands from boreal, temperate and tropical biomes. The occurrence of markers for Sphagnum, graminoids and lichens in all six studied peat deposits indicates that they persist in peat of thousands of years old, in different vegetation types and under different conditions. In order to facilitate the quantification of biomarkers from pyrolysates, typically expressed as proportion (%) of the total quantified pyrolysis products, an internal standard (5-α-androstane) was introduced. Depth records of the Sphagnum marker 4-isopropenylphenol from the upper 3 m of a Sphagnum-dominated peat, from samples analysed with and without internal standard showed a strong positive correlation (r2 = 0.72, P use of analytical pyrolysis in biomarker research by avoiding quantification of a high number of products.

Addressing small sample size bias in multiple-biomarker trials: Inclusion of biomarker-negative patients and Firth correction.

Science.gov (United States)

Habermehl, Christina; Benner, Axel; Kopp-Schneider, Annette

2018-03-01

In recent years, numerous approaches for biomarker-based clinical trials have been developed. One of these developments are multiple-biomarker trials, which aim to investigate multiple biomarkers simultaneously in independent subtrials. For low-prevalence biomarkers, small sample sizes within the subtrials have to be expected, as well as many biomarker-negative patients at the screening stage. The small sample sizes may make it unfeasible to analyze the subtrials individually. This imposes the need to develop new approaches for the analysis of such trials. With an expected large group of biomarker-negative patients, it seems reasonable to explore options to benefit from including them in such trials. We consider advantages and disadvantages of the inclusion of biomarker-negative patients in a multiple-biomarker trial with a survival endpoint. We discuss design options that include biomarker-negative patients in the study and address the issue of small sample size bias in such trials. We carry out a simulation study for a design where biomarker-negative patients are kept in the study and are treated with standard of care. We compare three different analysis approaches based on the Cox model to examine if the inclusion of biomarker-negative patients can provide a benefit with respect to bias and variance of the treatment effect estimates. We apply the Firth correction to reduce the small sample size bias. The results of the simulation study suggest that for small sample situations, the Firth correction should be applied to adjust for the small sample size bias. Additional to the Firth penalty, the inclusion of biomarker-negative patients in the analysis can lead to further but small improvements in bias and standard deviation of the estimates. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Curcumin improves alcoholic fatty liver by inhibiting fatty acid biosynthesis.

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Guo, Chang; Ma, Jingfan; Zhong, Qionghong; Zhao, Mengyuan; Hu, Tianxing; Chen, Tong; Qiu, Longxin; Wen, Longping

2017-08-01

Alcoholic fatty liver is a threat to human health. It has been long known that abstinence from alcohol is the most effective therapy, other effective therapies are not available for the treatment in humans. Curcumin has a great potential for anti-oxidation and anti-inflammation, but the effect on metabolic reconstruction remains little known. Here we performed metabolomic analysis by gas chromatography/mass spectrometry and explored ethanol pathogenic insight as well as curcumin action pattern. We identified seventy-one metabolites in mouse liver. Carbohydrates and lipids were characteristic categories. Pathway analysis results revealed that ethanol-induced pathways including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and pentose and glucuronate interconversions were suppressed by curcumin. Additionally, ethanol enhanced galactose metabolism and pentose phosphate pathway. Glyoxylate and dicarboxylate metabolism and pyruvate metabolism were inhibited in mice fed ethanol diet plus curcumin. Stearic acid, oleic acid and linoleic acid were disease biomarkers and therapical biomarkers. These results reflect the landscape of hepatic metabolism regulation. Our findings illustrate ethanol pathological pathway and metabolic mechanism of curcumin therapy. Copyright © 2017. Published by Elsevier Inc.

Identification of Biomarkers for Defense Response to Plasmopara viticola in a Resistant Grape Variety

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Giulia Chitarrini

2017-09-01

Full Text Available Downy mildew (Plasmopara viticola is one of the most destructive diseases of the cultivated species Vitis vinifera. The use of resistant varieties, originally derived from backcrosses of North American Vitis spp., is a promising solution to reduce disease damage in the vineyards. To shed light on the type and the timing of pathogen-triggered resistance, this work aimed at discovering biomarkers for the defense response in the resistant variety Bianca, using leaf discs after inoculation with a suspension of P. viticola. We investigated primary and secondary metabolism at 12, 24, 48, and 96 h post-inoculation (hpi. We used methods of identification and quantification for lipids (LC-MS/MS, phenols (LC-MS/MS, primary compounds (GC-MS, and semi-quantification for volatile compounds (GC-MS. We were able to identify and quantify or semi-quantify 176 metabolites, among which 53 were modulated in response to pathogen infection. The earliest changes occurred in primary metabolism at 24–48 hpi and involved lipid compounds, specifically unsaturated fatty acid and ceramide; amino acids, in particular proline; and some acids and sugars. At 48 hpi, we also found changes in volatile compounds and accumulation of benzaldehyde, a promoter of salicylic acid-mediated defense. Secondary metabolism was strongly induced only at later stages. The classes of compounds that increased at 96 hpi included phenylpropanoids, flavonols, stilbenes, and stilbenoids. Among stilbenoids we found an accumulation of ampelopsin H + vaticanol C, pallidol, ampelopsin D + quadrangularin A, Z-miyabenol C, and α-viniferin in inoculated samples. Some of these compounds are known as phytoalexins, while others are novel biomarkers for the defense response in Bianca. This work highlighted some important aspects of the host response to P. viticola in a commercial variety under controlled conditions, providing biomarkers for a better understanding of the mechanism of plant defense and a

Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of U.S. adults.

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Pfeiffer, Christine M; Sternberg, Maya R; Schleicher, Rosemary L; Rybak, Michael E

2013-06-01

Biochemical indicators of water-soluble vitamin (WSV) status were measured in a nationally representative sample of the U.S. population in NHANES 2003-2006. To examine whether demographic differentials in nutritional status were related to and confounded by certain variables, we assessed the association of sociodemographic (age, sex, race-ethnicity, education, income) and lifestyle (dietary supplement use, smoking, alcohol consumption, BMI, physical activity) variables with biomarkers of WSV status in adults (aged ≥ 20 y): serum and RBC folate, serum pyridoxal-5'-phosphate (PLP), serum 4-pyridoxic acid, serum total cobalamin (vitamin B-12), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA), and serum ascorbic acid. Age (except for PLP) and smoking (except for MMA) were generally the strongest significant correlates of these biomarkers (|r| ≤ 0.43) and together with supplement use explained more of the variability compared with the other covariates in bivariate analysis. In multiple regression models, sociodemographic and lifestyle variables together explained from 7 (vitamin B-12) to 29% (tHcy) of the biomarker variability. We observed significant associations for most biomarkers (≥ 6 of 8) with age, sex, race-ethnicity, supplement use, smoking, and BMI and for some biomarkers with PIR (5 of 8), education (1 of 8), alcohol consumption (4 of 8), and physical activity (5 of 8). We noted large estimated percentage changes in biomarker concentrations between race-ethnic groups (from -24 to 20%), between supplement users and nonusers (from -12 to 104%), and between smokers and nonsmokers (from -28 to 8%). In summary, age, sex, and race-ethnic differentials in biomarker concentrations remained significant after adjusting for sociodemographic and lifestyle variables. Supplement use and smoking were important correlates of biomarkers of WSV status.

Biomarkers in Airway Diseases

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Janice M Leung

2013-01-01

Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

Validation of biomarkers of food intake − critical assessment of candidate biomarkers

DEFF Research Database (Denmark)

Dragsted, Lars Ove; Gao, Qian; Scalbert, Augustin

2018-01-01

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promis...

Pollution biomarkers in the spiny lizard (Sceloporus spp.) from two suburban populations of Monterrey, Mexico.

Science.gov (United States)

Aguilera, Carlos; del Pliego, Pamela González; Alfaro, Roberto Mendoza; Lazcano, David; Cruz, Julio

2012-11-01

Environmental pollution may severely impact reptile species in urbanized areas. The magnitude of the impact is analyzed in the present study using lizard tail tips for the quantitative evaluation of enzymatic biomarkers of pollution. Spiny lizards (Sceloporus serrifer and S. torquatus) were collected from two suburban localities in the Monterrey metropolitan area, Mexico: Chipinque Ecological Park, a natural protected area, and El Carmen Industrial Park (IP), a highly polluted site. Different enzymes were used as biomarkers including: acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carboxylesterase (CaE), alkaline phosphatase (ALP), acid phosphatase (ACP), superoxide dismutase (SOD) and glutathione S-transferase (GST). The levels of AChE, BChE and ACP activity were not significantly different between localities. AChE and BChE, commonly used as biomarkers of neurotoxic polluting agents (e.g. organophosphate pesticides) do not appear to be affecting the populations from the study locations. In contrast, the levels of CaE, GST, ALP and SOD were significantly different between the localities. These biomarkers are regularly associated with oxidative stress and processes of detoxification, and generally indicate pollution caused by heavy metals or hydrocarbons, which are common in industrial sites. The data resulting from the analysis of these biomarkers indicate that these polluting agents are affecting the populations of Sceloporus in IP. The present work validates the possibility of conducting additional ecotoxicological studies using biomarkers in combination with a nondestructive sampling technique in species of spiny lizards that are abundant in many North America areas.

The emulsifying effect of biosurfactants produced by food spoilage organisms in Nigeria

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Christianah O. Ogunmola

2016-04-01

Full Text Available Food spoilage organisms were isolated using standard procedures on Nutrient Agar, Cetrimide Agar and Pseudomonas Agar Base (supplemented with CFC. The samples were categorized as animal products (raw fish, egg, raw chicken, corned beef, pasteurized milk and plant products (vegetable salad, water leaf (Talinium triangulare, boiled rice, tomatoes and pumpkin leaf (Teifairia occidentalis.They were characterised as Pseudomonas putida, Pseudomonas aeruginosa, Pseudomonas stutzeri, Burkholderia pseudomallei, Serratia rubidaea, Corynebacterium pilosum, Bacillus subtilis, Bacillus mycoides, Bacillus laterosporus, Bacillus laterosporus, Serratia marcescens, Bacillus cereus, Bacillus macerans, Alcaligenes faecalis and Alcaligenes eutrophus. Preliminary screening for biosurfactant production was done using red blood haemolysis test and confirmed by slide test, drop collapse and oil spreading assay. The biosurfactant produced was purified using acetone and the composition determined initially using Molisch’s test, thin layer chromatography and gas chromatography mass spectrometry. The components were found to be ethanol, amino acids, butoxyacetic acid, hexadecanoic acid, oleic acid, lauryl peroxide, octadecanoic acid and phthalic acid. The producing organisms grew readily on several hydrocarbons such as crude oil, diesel oil and aviation fuel when used as sole carbon sources.  The purified biosurfactants produced were able to cause emulsification of kerosene (19.71-27.14% as well as vegetable oil (16.91-28.12% based on the emulsification index. This result suggests that the isolates can be an asset and further work can exploit their optimal potential in industries.

Effect of eicosapentaenoic and docosahexaenoic acid on resting and exercise-induced inflammatory and oxidative stress biomarkers: a randomized, placebo controlled, cross-over study

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Galpin Andrew J

2009-08-01

Full Text Available Abstract Background The purpose of the present investigation was to determine the effects of EPA/DHA supplementation on resting and exercise-induced inflammation and oxidative stress in exercise-trained men. Fourteen men supplemented with 2224 mg EPA+2208 mg DHA and a placebo for 6 weeks in a random order, double blind cross-over design (with an 8 week washout prior to performing a 60 minute treadmill climb using a weighted pack. Blood was collected pre and post exercise and analyzed for a variety of oxidative stress and inflammatory biomarkers. Blood lactate, muscle soreness, and creatine kinase activity were also measured. Results Treatment with EPA/DHA resulted in a significant increase in blood levels of both EPA (18 ± 2 μmol·L-1 vs. 143 ± 23 μmol·L-1; p -1 vs. 157 ± 13 μmol·L-1; p 0.05. There was a mild increase in oxidative stress in response to exercise (XO and H2O2 (p Conclusion EPA/DHA supplementation increases blood levels of these fatty acids and results in decreased resting levels of inflammatory biomarkers in exercise-trained men, but does not appear necessary for exercise-induced attenuation in either inflammation or oxidative stress. This may be due to the finding that trained men exhibit a minimal increase in both inflammation and oxidative stress in response to moderate duration (60 minute aerobic exercise.

Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkers.

Science.gov (United States)

Chiu, Yu-Han; Williams, Paige L; Mínguez-Alarcón, Lidia; Gillman, Matthew; Sun, Qi; Ospina, Maria; Calafat, Antonia M; Hauser, Russ; Chavarro, Jorge E

2018-01-01

We developed a pesticide residue burden score (PRBS) based on a food frequency questionnaire and surveillance data on food pesticide residues to characterize dietary exposure over the past year. In the present study, we evaluated the association of the PRBS with urinary concentrations of pesticide biomarkers. Fruit and vegetable (FV) intake was classified as having high (PRBS≥4) or low (PRBSEARTH study. Two urine samples per man were analyzed for seven biomarkers of organophosphate and pyrethroid insecticides, and the herbicide 2,4-dichlorophenoxyacetic acid. We used generalized estimating equations to analyze the association of the PRBS with urinary concentrations of pesticide biomarkers. Urinary concentrations of pesticide biomarkers were positively related to high pesticide FV intake but inversely related to low pesticide FV intake. The molar sum of urinary concentrations of pesticide biomarkers was 21% (95% confidence interval (CI): 2%, 44%) higher for each one serving/day increase in high pesticide FV intake, and 10% (95% CI: 1%, 18%) lower for each one serving/day increase in low pesticide FV intake. Furthermore, intake of high pesticide FVs positively related to most individual urinary biomarkers. Our findings support the usefulness of the PRBS approach to characterize dietary exposure to select pesticides.

Early-Phase Studies of Biomarkers

DEFF Research Database (Denmark)

Pepe, Margaret S.; Janes, Holly; Li, Christopher I.

2016-01-01

of a positive biomarker test in cases (true positive) to cost associated with a positive biomarker test in controls (false positive). Guidance is offered on soliciting the cost/benefit ratio. The calculations are based on the longstanding decision theory concept of providing a net benefit on average...... impact on patient outcomes of using the biomarker to make clinical decisions....

Gas chromatography-mass spectrometry of ethyl palmitate calibration and resolution with ethyl oleate as biomarker ethanol sub acute in urine application study

Science.gov (United States)

Suaniti, Ni Made; Manurung, Manuntun

2016-03-01

Gas Chromatography-Mass Spectrometry is used to separate two and more compounds and identify fragment ion specific of biomarker ethanol such as palmitic acid ethyl ester (PAEE), as one of the fatty acid ethyl esters as early detection through conyugated reaction. This study aims to calibrate ethyl palmitate and develop analysis with oleate acid. This methode can be used analysis ethanol and its chemistry biomarker in ethanol sub-acute consumption as analytical forensic toxicology. The result show that ethanol level in urine rats Wistar were 9.21 and decreased 6.59 ppm after 48 hours consumption. Calibration curve of ethyl palmitate was y = 0.2035 x + 1.0465 and R2 = 0.9886. Resolution between ethyl palmitate and oleate were >1.5 as good separation with fragment ion specific was 88 and the retention time was 18 minutes.

Non-enzymatic lipid oxidation products in biological systems: assessment of the metabolites from polyunsaturated fatty acids.

Science.gov (United States)

Vigor, Claire; Bertrand-Michel, Justine; Pinot, Edith; Oger, Camille; Vercauteren, Joseph; Le Faouder, Pauline; Galano, Jean-Marie; Lee, Jetty Chung-Yung; Durand, Thierry

2014-08-01

Metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids notably omega-3 and omega-6 fatty acids have become important biomarkers of lipid products. Especially the arachidonic acid-derived F2-isoprostanes are the classic in vivo biomarker for oxidative stress in biological systems. In recent years other isoprostanes from eicosapentaenoic, docosahexaenoic, adrenic and α-linolenic acids have been evaluated, namely F3-isoprostanes, F4-neuroprostanes, F2-dihomo-isoprostanes and F1-phytoprostanes, respectively. These have been gaining interest as complementary specific biomarkers in human diseases. Refined extraction methods, robust analysis and elucidation of chemical structures have improved the sensitivity of detection in biological tissues and fluids. Previously the main reliable instrumentation for measurement was gas chromatography-mass spectrometry (GC-MS), but now the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunological techniques is gaining much attention. In this review, the types of prostanoids generated from non-enzymatic lipid peroxidation of some important omega-3 and omega-6 fatty acids and biological samples that have been determined by GC-MS and LC-MS/MS are discussed. Copyright © 2014. Published by Elsevier B.V.

Use of blood biomarkers to screen for obstructive sleep apnea

Directory of Open Access Journals (Sweden)

Fleming WE

2018-06-01

Full Text Available Wesley Elon Fleming,1 Jon-Erik C Holty,2 Richard K Bogan,3 Dennis Hwang,4 Aliya S Ferouz-Colborn,4 Rohit Budhiraja,5 Susan Redline,5 Edith Mensah-Osman,6 Nadir Ishag Osman,6 Qing Li,7 Armaghan Azad,1 Susann Podolak,1 Michael K Samoszuk,8 Amabelle B Cruz,8 Yang Bai,8 Jiuliu Lu,8 John S Riley,8 Paula C Southwick8 1Sleep Center Orange County, Irvine, CA, USA; 2Stanford Medical School, VA Palo Alto Health Care System, Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA; 3SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA; 4Sleep Medicine Department, Southern California Permanente Medical Group, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA; 5Division of Sleep Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA; 6EENA Comprehensive Neurology and Sleep Center, Boynton Beach, FL, USA; 7South Bend Medical Foundation, New Technology and Test Development, South Bend, IN, USA; 8Clinical Research Department, Beckman Coulter, Inc., Brea, CA, USAPurpose: Obstructive sleep apnea (OSA is a highly prevalent disorder associated with increased risk for cardiovascular disease, diabetes, and other chronic conditions. Unfortunately, up to 90% of individuals with OSA remain without a diagnosis or therapy. We assess the relationship between OSA and blood biomarkers, and test the hypothesis that combinations of markers provide a characteristic OSA signature with diagnostic screening value. This validation study was conducted in an independent cohort in order to replicate findings from a prior feasibility study.Patients and methods: This multicenter prospective study consecutively enrolled adult male subjects with clinically suspected OSA. All subjects underwent overnight sleep studies. An asymptomatic control group was also obtained. Five biomarkers were tested: glycated hemoglobin (HbA1c, C-reactive protein (CRP, uric acid, erythropoietin (EPO, and interleukin-6 (IL-6.Results: The study

Biomarkers of PTSD: military applications and considerations.

Science.gov (United States)

Lehrner, Amy; Yehuda, Rachel

2014-01-01

Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Implementation of proteomic biomarkers: making it work

Science.gov (United States)

Mischak, Harald; Ioannidis, John PA; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

2012-01-01

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. PMID:22519700

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

International Nuclear Information System (INIS)

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-01-01

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

Energy Technology Data Exchange (ETDEWEB)

Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

DNA Methylation Biomarkers: Cancer and Beyond

Directory of Open Access Journals (Sweden)

Thomas Mikeska

2014-09-01

Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

Lignin in the Organic Matter of the Soils of the Russian Plain as Biomarker of Palaeoenvironment

Science.gov (United States)

Kovalev, I. V.; Kovaleva, N. O.

2018-01-01

It has been shown by the methods of biochemistry, nuclear magnetic resonance, and isotope geochemistry that the proportions of lignin phenols may be used as molecular traces of paleovegetation due to their biochemical and physiological specificity and high resistance to decomposition. Lignin structures have been detected in soils and in iron-manganese concretions. The comparison of the 13C NMR spectra of native lignin preparations isolated from different woody and herbaceous species with those of soil humic acids makes it possible to identify many characteristic shifts of lignin nature in humic acids at 56, 102, 115, 119, 131, 147, 151-152, 160, and 166 ppm. The information role of biomarker has been tested at the reconstruction of paleovegetation in the uplands of the Russian Plain. The representativeness of information has been increased using the isotope analysis (δ13C) and the radiocarbon dating; a new parameter—the composition of lignin phenols—has been introduced to the existing system of biomarkers.

Identification of hepatic biomarkers for physiological imbalance of dairy cows in early and mid lactation using proteomic technology

DEFF Research Database (Denmark)

Moyes, Kasey; Bendixen, Emøke; Codrea, Marius Cosmin

2013-01-01

the ration with 60% wheat straw. Liver biopsies were collected −1 and 3 d relative to restriction. Before restriction, an index for PI was calculated based on plasma nonesterified fatty acids, β-hydroxybutyrate, and glucose concentrations. Within E and M cows, a subsets of 6 cow was classified as having...... as potential hepatic biomarkers for PI for cows during early lactation and alcohol dehydrogenase-4 and methylmalonate-semialdehyde dehydrogenase for cows in mid lactation. This preliminary study identified new biomarkers in liver for PI and provided a better understanding of the differences in coping...

Lipid biomarkers in Holocene and glacial sediments from ancient Lake Ohrid (Macedonia, Albania

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J. Holtvoeth

2010-11-01

Full Text Available Organic matter preserved in Lake Ohrid sediments originates from aquatic and terrestrial sources. Its variable composition reflects climate-controlled changes in the lake basin's hydrology and related organic matter export, i.e. changes in primary productivity, terrestrial plant matter input and soil erosion. Here, we present first results from lipid biomarker investigations of Lake Ohrid sediments from two near-shore settings: site Lz1120 near the southern shore, with low-lying lands nearby and probably influenced by river discharge, and site Co1202 which is close to the steep eastern slopes. Variable proportions of terrestrial n-alkanoic acids and n-alkanols as well as compositional changes of ω-hydroxy acids document differences in soil organic matter supply between the sites and during different climate stages (glacial, Holocene, 8.2 ka cooling event. Changes in the vegetation cover are suggested by changes in the dominant chain length of terrestrial n-alkanols. Effective microbial degradation of labile organic matter and in situ contribution of organic matter derived from the microbes themselves are both evident in the sediments. We found evidence for anoxic conditions within the photic zone by detecting epicholestanol and tetrahymanol from sulphur-oxidising phototrophic bacteria and bacterivorous ciliates and for the influence of a settled human community from the occurrence of coprostanol, a biomarker for human and animal faeces (pigs, sheep, goats, in an early Holocene sample. This study illustrates the potential of lipid biomarkers for future environmental reconstructions using one of Europe's oldest continental climate archives, Lake Ohrid.

Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of US adults1,2,3

Science.gov (United States)

Pfeiffer, Christine M.; Sternberg, Maya R.; Schleicher, Rosemary L.; Rybak, Michael E.

2016-01-01

Biochemical indicators of water-soluble vitamin (WSV) status have been measured in a nationally representative sample of the US population in NHANES 2003–2006. To examine whether demographic differentials in nutritional status were related to and confounded by certain variables, we assessed the association of sociodemographic (age, sex, race-ethnicity, education, income) and lifestyle variables (dietary supplement use, smoking, alcohol consumption, BMI, physical activity) with biomarkers of WSV status in adults (≥20 y): serum and RBC folate, serum pyridoxal-5′-phosphate (PLP), serum 4-pyridoxic acid, serum total cobalamin (B-12), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA), and serum ascorbic acid. Age (except for PLP) and smoking (except for MMA) were generally the strongest significant correlates of these biomarkers (|r| ≤0.43) and together with supplement use explained more of the variability as compared to the other covariates in bivariate analysis. In multiple regression models, sociodemographic and lifestyle variables together explained from 7% (B-12) to 29% (tHcy) of the biomarker variability. We observed significant associations for most biomarkers (≥6 out of 8) with age, sex, race-ethnicity, supplement use, smoking, and BMI; and for some biomarkers with PIR (5/8), education (1/8), alcohol consumption (4/8), and physical activity (5/8). We noted large estimated percent changes in biomarker concentrations between race-ethnic groups (from −24% to 20%), between supplement users and nonusers (from −12% to 104%), and between smokers and nonsmokers (from −28% to 8%). In summary, age, sex, and race-ethnic differentials in biomarker concentrations remained significant after adjusting for sociodemographic and lifestyle variables. Supplement use and smoking were important correlates of biomarkers of WSV status. PMID:23576641

Implementation of proteomic biomarkers: making it work.

Science.gov (United States)

Mischak, Harald; Ioannidis, John P A; Argiles, Angel; Attwood, Teresa K; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W; Julien, Bruce A; Lankisch, Tim; Leung, Hing Y; Maahs, David; Magni, Fulvio; Manns, Michael P; Manolis, Efthymios; Mayer, Gert; Navis, Gerjan; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P; Vlahou, Antonia

2012-09-01

While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare. © 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.

Biomarkers of PTSD: military applications and considerations

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Amy Lehrner

2014-08-01

Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

Correlations between Fruit, Vegetables, Fish, Vitamins, and Fatty Acids Estimated by Web-Based Nonconsecutive Dietary Records and Respective Biomarkers of Nutritional Status.

Science.gov (United States)

Lassale, Camille; Castetbon, Katia; Laporte, François; Deschamps, Valérie; Vernay, Michel; Camilleri, Géraldine M; Faure, Patrice; Hercberg, Serge; Galan, Pilar; Kesse-Guyot, Emmanuelle

2016-03-01

It is of major importance to measure the validity of self-reported dietary intake using web-based instruments before applying them in large-scale studies. This study aimed to validate self-reported intake of fish, fruit and vegetables, and selected micronutrient intakes assessed by a web-based self-administered dietary record tool used in the NutriNet-Santé prospective cohort study, against the following concentration biomarkers: plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acids. One hundred ninety-eight adult volunteers (103 men and 95 women, mean age=50.5 years) were included in the protocol: they completed 3 nonconsecutive-day dietary records and two blood samples were drawn 3 weeks apart. The study was conducted in the area of Paris, France, between October 2012 and May 2013. Reported fish, fruit and vegetables, and selected micronutrient intakes and plasma beta carotene, vitamin C, and n-3 polyunsaturated fatty acid levels were compared. Simple and adjusted Spearman's rank correlation coefficients were estimated after de-attenuation for intra-individual variation. Regarding food groups in men, adjusted correlations ranged from 0.20 for vegetables and plasma vitamin C to 0.49 for fruits and plasma vitamin C, and from 0.40 for fish and plasma c20:5 n-3 (eicosapentaenoic acid [EPA]) to 0.55 for fish and plasma c22:6 n-3 (docosahexaenoic acid). In women, correlations ranged from 0.13 (nonsignificant) for vegetables and plasma vitamin C to 0.41 for fruits and vegetables and plasma beta carotene, and from 0.27 for fatty fish and EPA to 0.54 for fish and EPA+docosahexaenoic acid. Regarding micronutrients, adjusted correlations ranged from 0.36 (EPA) to 0.58 (vitamin C) in men and from 0.32 (vitamin C) to 0.38 (EPA) in women. The findings suggest that three nonconsecutive web-based dietary records provide reasonable estimates of true intake of fruits, vegetables, fish, beta carotene, vitamin C, and n-3 fatty acids. Along with other validation

Mining biomarker information in biomedical literature

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Younesi Erfan

2012-12-01

Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

Using 3–6 differences in essential fatty acids rather than 3/6 ratios gives useful food balance scores

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Lands Bill

2012-05-01

Full Text Available Abstract Background The vitamin-like omega-3 and omega-6 essential fatty acids are converted in the body to a large family of hormones which act at selective receptors that occur on nearly every cell and tissue. A relative omega-3 deficit allows overabundant actions of omega-6 hormones to develop into health disorders. People need simple, explicit information on the balance of essential fatty acids in their foods to avoid accumulating unintended imbalances in their tissue omega-3 and omega-6 fatty acids. Results We developed an Omega 3–6 Balance Food Score that summarizes in a single value the balance among eleven omega-3 and omega-6 essential fatty acids in a food. The value allows a quantitative estimate of the impact of each food item on the proportions of omega-3 and omega-6 that will accumulate in the 20- and 22-carbon highly unsaturated fatty acids of blood, which is an important health risk assessment biomarker. Conclusions The impact of an individual food item upon a useful health risk assessment biomarker is easily evident in a simple, explicit value for the balance among eleven essential fatty acids nutrients. Foods with more positive Omega 3–6 Balance Food Scores will increase the percent of omega-3 in the biomarker, whereas those with more negative Scores will increase the percent of omega-6 in the biomarker.

Expression patterns of nicotinamide phosphoribosyltransferase and nicotinic acid phosphoribosyltransferase in human malignant lymphomas

DEFF Research Database (Denmark)

Olesen, Uffe Høgh; Hastrup, Nina; Sehested, Maxwell

2011-01-01

The purpose of the study was to determine in human malignant lymphomas the expression patterns of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinic acid phosphoribosyltransferase (NAPRT), the primary, rate-limiting enzymes in the synthesis of NAD+. NAMPT is a potential biomarker...... for sensitivity to NAMPT inhibitors and NAPRT is a biomarker for the use of nicotinic acid as a chemoprotectant in treatment with NAMPT inhibitors. The NAMPT inhibitor, APO866, is currently in clinical phase II trials in lymphomas. The expression of NAMPT and NAPRT was investigated in 53 samples of malignant.......0024). In conclusion, FL are a promising target for NAMPT inhibitors whereas substantial subsets of malignant lymphomas especially in Hodgkin lymphoma may be suitable for a combination treatment with nicotinic acid and NAMPT inhibitors....

Dietary and health biomarkers - time for an update

DEFF Research Database (Denmark)

Dragsted, Lars Ove; Gao, Qian; Pratico, Giulia

2017-01-01

for these biomarker classes, and no recent systematic review of all proposed biomarkers for food intake. While advanced databases exist for the human and food metabolomes, additional tools are needed to curate and evaluate current data on dietary and health biomarkers. The Food Biomarkers Alliance (FoodBAll) under......In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health...... much mechanistic insight into the effects of food components and diets. Although hundreds of papers in nutrition are published annually, there is no current ontology for the area, no generally accepted classification terminology for biomarkers in nutrition and health, no systematic validation scheme...

Biomarkers of HIV-associated Cancer

OpenAIRE

Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd

2014-01-01

Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of can...

Heart-type fatty acid-binding protein (H-FABP) as an early diagnostic biomarker in patients with acute chest pain.

Science.gov (United States)

Vupputuri, Anjith; Sekhar, Saritha; Krishnan, Sajitha; Venugopal, K; Natarajan, K U

2015-01-01

Heart-type fatty acid-binding protein (H-FABP) is an emerging biomarker, which was found to be sensitive for the early diagnosis of acute myocardial infarction (AMI). We prospectively investigated the usefulness of H-FABP determination for the evaluation of acute chest pain in patients arriving at the emergency department. Fifty-four patients presenting with acute ischemic chest pain were evaluated. H-FABP was estimated at admission using latex-enhanced immunoturbidimetric assay. Serial cardiac troponin I (cTnI), creatinine kinase-MB (CK-MB) determination, ischemia workup with stress testing, and/or coronary angiogram (CAG) were performed according to standard protocols. The sensitivity and specificity of H-FABP was 89.7% and 68%, for cTnI it was 62.1% and 100%, and for CK-MB it was 44.8% and 92%, respectively for diagnosis of AMI. The sensitivity of H-FABP was found to be far superior to initial cTnI and CK-MB, for those seen within 6h (100% vs. 46.1%, 33% respectively). On further evaluation of patients with positive H-FABP and negative cTnI, 71.4% of the patients had significant lesion on CAG, indicating ischemic cause of H-FABP elevation. Six patients with normal cTnI and CK-MB with high H-FABP had ST elevation on subsequent ECGs and were taken for primary angioplasty. H-FABP is a highly sensitive biomarker for the early diagnosis of AMI. H-FABP as early marker and cTnI as late marker would be the ideal combination to cover the complete diagnostic window for AMI. Detection of myocardial injury by H-FABP may also be applied in patients with unstable angina. H-FABP can also be used as a marker for early detection of STEMI before the ECG changes become apparent. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients.

Science.gov (United States)

Asemi, Zatollah; Soleimani, Alireza; Shakeri, Hossein; Mazroii, Navid; Esmaillzadeh, Ahmad

2016-11-01

The current study was carried out to assess the effects of omega-3 fatty acid and alpha-tocopherol co-supplementation on malnutrition-inflammation score (MIS), biomarkers of inflammation and oxidative stress in chronic hemodialysis (HD) patients. In a randomized double-blind placebo-controlled clinical trial, 120 patients with chronic HD were included. Patients were randomly allocated into four groups to receive: (1) 1250 mg/day omega-3 fatty acid containing 600 mg EPA and 300 mg DHA + alpha-tocopherol placebo (n = 30); (2) 400 IU/day alpha-tocopherol + omega-3 fatty acids placebo (n = 30); (3) 1250 mg omega-3 fatty acids/day + 400 IU/day alpha-tocopherol (n = 30); and (4) omega-3 fatty acids placebo + alpha-tocopherol placebo (n = 30) for 12 weeks. After 12 weeks of intervention, all three groups of alpha-tocopherol only, individual omega-3 fatty acids, and combined omega-3 fatty acids and alpha-tocopherol experienced a significant improvements in MIS compared with the placebo group; however, improvements were much greater in the individual omega-3 fats (-1.4 ± 1.4) and combined omega-3 fats and alpha-tocopherol (-1.1 ± 2.3) groups compared with alpha-tocopherol group alone (-0.5 ± 1.7, P = 0.004). Furthermore, both individual and combined intervention with omega-3 fats and alpha-tocopherol led to a significant increase in plasma nitric oxide (NO) (combined group: +17.6 ± 29.3; alpha-tocopherol: +43.1 ± 36.3; omega-3 fats: +31.0 ± 40.0; and placebo: -0.5 ± 18.5 µmol/L, respectively, P acids and alpha-tocopherol co-supplementation for 12 weeks among HD patients improved MIS, plasma NO and TAC levels. Future studies with longer duration of the intervention are needed to confirm the validity of our findings. CLINICAL REGISTRATION: www.irct.ir as IRCT201410245623N28.

Analysis of biomarker data a practical guide

CERN Document Server

Looney, Stephen W

2015-01-01

A "how to" guide for applying statistical methods to biomarker data analysis Presenting a solid foundation for the statistical methods that are used to analyze biomarker data, Analysis of Biomarker Data: A Practical Guide features preferred techniques for biomarker validation. The authors provide descriptions of select elementary statistical methods that are traditionally used to analyze biomarker data with a focus on the proper application of each method, including necessary assumptions, software recommendations, and proper interpretation of computer output. In addition, the book discusses

Production and Early Preservation of Lipid Biomarkers in Iron Hot Springs

Energy Technology Data Exchange (ETDEWEB)

Parenteau, Mary N.; Jahnke, Linda L.; Farmer, Jack D.; Cady, Sherry L.

2014-06-01

The bicarbonate-buffered anoxic vent waters at Chocolate Pots hot springs in Yellowstone National Park are 51–54°C, pH 5.5–6.0, and are very high in dissolved Fe(II) at 5.8–5.9 mg/L. The aqueous Fe(II) is oxidized by a combination of biotic and abiotic mechanisms and precipitated as primary siliceous nanophase iron oxyhydroxides (ferrihydrite). Four distinct prokaryotic photosynthetic microbial mat types grow on top of these iron deposits. Lipids were used to characterize the community composition of the microbial mats, link source organisms to geologically significant biomarkers, and investigate how iron mineralization degrades the lipid signature of the community. The phospholipid and glycolipid fatty acid profiles of the highest-temperature mats indicate that they are dominated by cyanobacteria and green nonsulfur filamentous anoxygenic phototrophs (FAPs). Diagnostic lipid biomarkers of the cyanobacteria include midchain branched mono- and dimethylalkanes and, most notably, 2-methylbacteriohopanepolyol. Diagnostic lipid biomarkers of the FAPs (Chloroflexus and Roseiflexus spp.) include wax esters and a long-chain tri-unsaturated alkene. Surprisingly, the lipid biomarkers resisted the earliest stages of microbial degradation and diagenesis to survive in the iron oxides beneath the mats. Understanding the potential of particular sedimentary environments to capture and preserve fossil biosignatures is of vital importance in the selection of the best landing sites for future astrobiological missions to Mars. Finally, this study explores the nature of organic degradation processes in moderately thermal Fe(II)-rich groundwater springs—environmental conditions that have been previously identified as highly relevant for Mars exploration.

Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration.

Science.gov (United States)

Khan, Gulafshana Hafeez; Galazis, Nicolas; Docheva, Nikolina; Layfield, Robert; Atiomo, William

2015-01-01

Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. If validated, these biomarkers could provide a useful framework for the knowledge infrastructure in this area. To accomplish this goal, a

Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

DEFF Research Database (Denmark)

Kücükakin, Bülent; Kocak, Volkan; Lykkesfeldt, Jens

2011-01-01

of buffy-coat reduced red cells in SAG-M additive solution, by assessing biomarkers of oxidative and inflammatory stress during a storage period of 35 days. Study design and methods. Ten units of RBCs were stored for 35 days. Samples were collected from the units at storage days 1, 3, 7, 14, 21, 28 and 35......, respectively. The samples were analysed for various biomarkers expressing the oxidative stress and inflammation, including malondialdehyde (MDA), α-tocopherol (AT), dehydroascorbic acid (DHA), ascorbate (ASC), YKL-40 and interleukin-6 (IL-6). Results. The levels ofMDA, ASC, DHA, IL-6 and YKL-40 changed...... significantly during the storage period (p oxidative and inflammatory stress during a storage period...

Proteomic and metabolomic approaches to biomarker discovery

CERN Document Server

Issaq, Haleem J

2013-01-01

Proteomic and Metabolomic Approaches to Biomarker Discovery demonstrates how to leverage biomarkers to improve accuracy and reduce errors in research. Disease biomarker discovery is one of the most vibrant and important areas of research today, as the identification of reliable biomarkers has an enormous impact on disease diagnosis, selection of treatment regimens, and therapeutic monitoring. Various techniques are used in the biomarker discovery process, including techniques used in proteomics, the study of the proteins that make up an organism, and metabolomics, the study of chemical fingerprints created from cellular processes. Proteomic and Metabolomic Approaches to Biomarker Discovery is the only publication that covers techniques from both proteomics and metabolomics and includes all steps involved in biomarker discovery, from study design to study execution.  The book describes methods, and presents a standard operating procedure for sample selection, preparation, and storage, as well as data analysis...

Effect of dark sweet cherry powder consumption on the gut microbiota, short-chain fatty acids, and biomarkers of gut health in obese db/db mice

Directory of Open Access Journals (Sweden)

Jose F. Garcia-Mazcorro

2018-01-01

Full Text Available Cherries are fruits containing fiber and bioactive compounds (e.g., polyphenolics with the potential of helping patients with diabetes and weight disorders, a phenomenon likely related to changes in the complex host-microbiota milieu. The objective of this study was to investigate the effect of cherry supplementation on the gut bacterial composition, concentrations of caecal short-chain fatty acids (SCFAs and biomarkers of gut health using an in vivo model of obesity. Obese diabetic (db/db mice received a supplemented diet with 10% cherry powder (supplemented mice, n = 12 for 12 weeks; obese (n = 10 and lean (n = 10 mice served as controls and received a standard diet without cherry. High-throughput sequencing of the 16S rRNA gene and quantitative real-time PCR (qPCR were used to analyze the gut microbiota; SCFAs and biomarkers of gut health were also measured using standard techniques. According to 16S sequencing, supplemented mice harbored a distinct colonic microbiota characterized by a higher abundance of mucin-degraders (i.e., Akkermansia and fiber-degraders (the S24-7 family as well as lower abundances of Lactobacillus and Enterobacteriaceae. Overall this particular cherry-associated colonic microbiota did not resemble the microbiota in obese or lean controls based on the analysis of weighted and unweighted UniFrac distance metrics. qPCR confirmed some of the results observed in sequencing, thus supporting the notion that cherry supplementation can change the colonic microbiota. Moreover, the SCFAs detected in supplemented mice (caproate, methyl butyrate, propionate, acetate and valerate exceeded those concentrations detected in obese and lean controls except for butyrate. Despite the changes in microbial composition and SCFAs, most of the assessed biomarkers of inflammation, oxidative stress, and intestinal health in colon tissues and mucosal cells were similar in all obese mice with and without supplementation. This paper shows

Biomarkers of latent TB infection

DEFF Research Database (Denmark)

Ruhwald, Morten; Ravn, Pernille

2009-01-01

For the last 100 years, the tuberculin skin test (TST) has been the only diagnostic tool available for latent TB infection (LTBI) and no biomarker per se is available to diagnose the presence of LTBI. With the introduction of M. tuberculosis-specific IFN-gamma release assays (IGRAs), a new area...... of in vitro immunodiagnostic tests for LTBI based on biomarker readout has become a reality. In this review, we discuss existing evidence on the clinical usefulness of IGRAs and the indefinite number of potential new biomarkers that can be used to improve diagnosis of latent TB infection. We also present...... early data suggesting that the monocyte-derived chemokine inducible protein-10 may be useful as a novel biomarker for the immunodiagnosis of latent TB infection....

Integrated preservation and sample clean up procedures for studying water ingestion by recreational swimmers via urinary biomarker determination.

Science.gov (United States)

Cantú, Ricardo; Shoemaker, Jody A; Kelty, Catherine A; Wymer, Larry J; Behymer, Thomas D; Dufour, Alfred P; Magnuson, Matthew L

2017-08-22

The use of cyanuric acid as a biomarker for ingestion of swimming pool water may lead to quantitative knowledge of the volume of water ingested during swimming, contributing to a better understanding of disease resulting from ingestion of environmental contaminants. When swimming pool water containing chlorinated cyanurates is inadvertently ingested, cyanuric acid is excreted quantitatively within 24 h as a urinary biomarker of ingestion. Because the volume of water ingested can be quantitatively estimated by calculation from the concentration of cyanuric acid in 24 h urine samples, a procedure for preservation, cleanup, and analysis of cyanuric acid was developed to meet the logistical demands of large scale studies. From a practical stand point, urine collected from swimmers cannot be analyzed immediately, given requirements of sample collection, shipping, handling, etc. Thus, to maintain quality control to allow confidence in the results, it is necessary to preserve the samples in a manner that ensures as quantitative analysis as possible. The preservation and clean-up of cyanuric acid in urine is complicated because typical approaches often are incompatible with the keto-enol tautomerization of cyanuric acid, interfering with cyanuric acid sample preparation, chromatography, and detection. Therefore, this paper presents a novel integration of sample preservation, clean-up, chromatography, and detection to determine cyanuric acid in 24 h urine samples. Fortification of urine with cyanuric acid (0.3-3.0 mg/L) demonstrated accuracy (86-93% recovery) and high reproducibility (RSD urine suggested sufficient cyanuric acid stability for sample collection procedures, while longer holding times suggested instability of the unpreserved urine. Preserved urine exhibited a loss of around 0.5% after 22 days at refrigerated storage conditions of 4 °C. Published by Elsevier B.V.

Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure

Energy Technology Data Exchange (ETDEWEB)

Shannahan, Jonathan H. [Curriculum in Toxicology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Alzate, Oscar [Systems Proteomics Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599 (United States); Winnik, Witold M.; Andrews, Debora [Proteomics Core, Research Core Unit, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Schladweiler, Mette C. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Ghio, Andrew J. [Clinical Research Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Chapel Hill, NC 27599 (United States); Gavett, Stephen H. [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States); Kodavanti, Urmila P., E-mail: Kodavanti.Urmila@epa.gov [Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711 (United States)

2012-04-15

Identification of biomarkers assists in the diagnosis of disease and the assessment of health risks from environmental exposures. We hypothesized that rats exposed to Libby amphibole (LA) would present with a unique serum proteomic profile which could help elucidate epidemiologically-relevant biomarkers. In four experiments spanning varied protocols and temporality, healthy (Wistar Kyoto, WKY; and F344) and cardiovascular compromised (CVD) rat models (spontaneously hypertensive, SH; and SH heart failure, SHHF) were intratracheally instilled with saline (control) or LA. Serum biomarkers of cancer, inflammation, metabolic syndrome (MetS), and the acute phase response (APR) were analyzed. All rat strains exhibited acute increases in α-2-macroglobulin, and α1-acid glycoprotein. Among markers of inflammation, lipocalin-2 was induced in WKY, SH and SHHF and osteopontin only in WKY after LA exposure. While rat strain- and age-related changes were apparent in MetS biomarkers, no LA effects were evident. The cancer marker mesothelin was increased only slightly at 1 month in WKY in one of the studies. Quantitative Intact Proteomic profiling of WKY serum at 1 day or 4 weeks after 4 weekly LA instillations indicated no oxidative protein modifications, however APR proteins were significantly increased. Those included serine protease inhibitor, apolipoprotein E, α-2-HS-glycoprotein, t-kininogen 1 and 2, ceruloplasmin, vitamin D binding protein, serum amyloid P, and more 1 day after last LA exposure. All changes were reversible after a short recovery regardless of the acute or long-term exposures. Thus, LA exposure induces an APR and systemic inflammatory biomarkers that could have implications in systemic and pulmonary disease in individuals exposed to LA. -- Highlights: ► Biomarkers of asbestos exposure are required for disease diagnosis. ► Libby amphibole exposure is associated with increased human mortality. ► Libby amphibole increases circulating proteins involved

Fluid biomarkers in multiple system atrophy

DEFF Research Database (Denmark)

Laurens, Brice; Constantinescu, Radu; Freeman, Roy

2015-01-01

Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure

Science.gov (United States)

Nath, Anjali K.; Roberts, Lee D.; Liu, Yan; Mahon, Sari B.; Kim, Sonia; Ryu, Justine H.; Werdich, Andreas; Januzzi, James L.; Boss, Gerry R.; Rockwood, Gary A.; MacRae, Calum A.; Brenner, Matthew; Gerszten, Robert E.; Peterson, Randall T.

2013-01-01

Exposure to cyanide causes a spectrum of cardiac, neurological, and metabolic dysfunctions that can be fatal. Improved cyanide antidotes are needed, but the ideal biological pathways to target are not known. To understand better the metabolic effects of cyanide and to discover novel cyanide antidotes, we developed a zebrafish model of cyanide exposure and scaled it for high-throughput chemical screening. In a screen of 3120 small molecules, we discovered 4 novel antidotes that block cyanide toxicity. The most potent antidote was riboflavin. Metabolomic profiling of cyanide-treated zebrafish revealed changes in bile acid and purine metabolism, most notably by an increase in inosine levels. Riboflavin normalizes many of the cyanide-induced neurological and metabolic perturbations in zebrafish. The metabolic effects of cyanide observed in zebrafish were conserved in a rabbit model of cyanide toxicity. Further, humans treated with nitroprusside, a drug that releases nitric oxide and cyanide ions, display increased circulating bile acids and inosine. In summary, riboflavin may be a novel treatment for cyanide toxicity and prophylactic measure during nitroprusside treatment, inosine may serve as a biomarker of cyanide exposure, and metabolites in the bile acid and purine metabolism pathways may shed light on the pathways critical to reversing cyanide toxicity.—Nath, A. K., Roberts, L. D., Liu, Y., Mahon, S. B., Kim, S., Ryu, J. H., Werdich, A., Januzzi, J. L., Boss, G. R., Rockwood, G. A., MacRae, C. A., Brenner, M., Gerszten, R. E., Peterson, R. T. Chemical and metabolomic screens identify novel biomarkers and antidotes for cyanide exposure. PMID:23345455

Seminal plasma as a source of prostate cancer peptide biomarker candidates for detection of indolent and advanced disease.

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Jochen Neuhaus

Full Text Available BACKGROUND: Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease. METHODOLOGY/PRINCIPAL FINDINGS: In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls were enrolled in 3 centres. Biomarker panels a for PCa diagnosis (comparison of PCa patients versus benign controls and b for advanced disease (comparison of patients with post surgery Gleason score 7 were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study. CONCLUSIONS/SIGNIFICANCE: Seminal plasma represents a robust source of potential peptide makers

Allergic asthma biomarkers using systems approaches

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Gaurab eSircar

2014-01-01

Full Text Available Asthma is characterized by lung inflammation caused by complex interaction between the immune system and environmental factors such as allergens and inorganic pollutants. Recent research in this field is focused on discovering new biomarkers associated with asthma pathogenesis. This review illustrates updated research associating biomarkers of allergic asthma and their potential use in systems biology of the disease. We focus on biomolecules with altered expression, which may serve as inflammatory, diagnostic and therapeutic biomarkers of asthma discovered in human or experimental asthma model using genomic, proteomic and epigenomic approaches for gene and protein expression profiling. These include high-throughput technologies such as state of the art microarray and proteomics Mass Spectrometry (MS platforms. Emerging concepts of molecular interactions and pathways may provide new insights in searching potential clinical biomarkers. We summarized certain pathways with significant linkage to asthma pathophysiology by analyzing the compiled biomarkers. Systems approaches with this data can identify the regulating networks, which will eventually identify the key biomarkers to be used for diagnostics and drug discovery.

Lipid biomarkers in Symbiodinium dinoflagellates: new indicators of thermal stress

KAUST Repository

Kneeland, J.

2013-08-30

Lipid content and fatty acid profiles of corals and their dinoflagellate endosymbionts are known to vary in response to high-temperature stress. To better understand the heat-stress response in these symbionts, we investigated cultures of Symbiodinium goreauii type C1 and Symbiodinium sp. clade subtype D1 grown under a range of temperatures and durations. The predominant lipids produced by Symbiodinium are palmitic (C16) and stearic (C18) saturated fatty acids and their unsaturated analogs, the polyunsaturated fatty acid docosahexaenoic acid (C22:6, n-3; DHA), and a variety of sterols. Prolonged exposure to high temperature causes the relative amount of unsaturated acids within the C18 fatty acids in Symbiodinium tissue to decrease. Thermal stress also causes a decrease in abundance of fatty acids relative to sterols, as well as the more specific ratio of DHA to an algal 4-methyl sterol. These shifts in fatty acid unsaturation and fatty acid-to-sterol ratios are common to both types C1 and D1, but the apparent thermal threshold of lipid changes is lower for type C1. This work indicates that ratios among free fatty acids and sterols in Symbiodinium can be used as sensitive indicators of thermal stress. If the Symbiodinium lipid stress response is unchanged in hospite, the algal heat-stress biomarkers we have identified could be measured to detect thermal stress within the coral holobiont. These results provide new insights into the potential role of lipids in the overall Symbiodinium thermal stress response. © 2013 Springer-Verlag Berlin Heidelberg.

Towards understanding and predicting suicidality in women: biomarkers and clinical risk assessment.

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Levey, D F; Niculescu, E M; Le-Niculescu, H; Dainton, H L; Phalen, P L; Ladd, T B; Weber, H; Belanger, E; Graham, D L; Khan, F N; Vanipenta, N P; Stage, E C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R; Niculescu, A B

2016-06-01

then showed how the clinical information apps combined with the 50 validated biomarkers into a broad predictor (UP-Suicide), our apriori primary end point, predicts suicidality in women. UP-Suicide had a receiver-operating characteristic (ROC) area under the curve (AUC) of 82% for predicting SI and an AUC of 78% for predicting future hospitalizations for suicidality. Some of the individual components of the UP-Suicide showed even better results. SASS had an AUC of 81% for predicting SI, CFI-S had an AUC of 84% and the combination of the two apps had an AUC of 87%. The top biomarker from our sequential discovery, prioritization and validation steps, BCL2, predicted future hospitalizations due to suicidality with an AUC of 89%, and the panel of 50 validated biomarkers (BioM-50) predicted future hospitalizations due to suicidality with an AUC of 94%. The best overall single blood biomarker for predictions was PIK3C3 with an AUC of 65% for SI and an AUC of 90% for future hospitalizations. Finally, we sought to understand the biology of the biomarkers. BCL2 and GSK3B, the top CFG scoring validated biomarkers, as well as PIK3C3, have anti-apoptotic and neurotrophic effects, are decreased in expression in suicidality and are known targets of the anti-suicidal mood stabilizer drug lithium, which increases their expression and/or activity. Circadian clock genes were overrepresented among the top markers. Notably, PER1, increased in expression in suicidality, had an AUC of 84% for predicting future hospitalizations, and CSNK1A1, decreased in expression, had an AUC of 96% for predicting future hospitalizations. Circadian clock abnormalities are related to mood disorder, and sleep abnormalities have been implicated in suicide. Docosahexaenoic acid signaling was one of the top biological pathways overrepresented in validated biomarkers, which is of interest given the potential therapeutic and prophylactic benefits of omega-3 fatty acids. Some of the top biomarkers from the current

Urinary Biomarkers of Brain Diseases

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Manxia An

2015-12-01

Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

Science.gov (United States)

Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

2012-12-01

To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

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Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

2012-01-17

This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Supercritical Fluid Extraction of Bacterial and Archaeal Lipid Biomarkers from Anaerobically Digested Sludge

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Koichi Fujie

2012-03-01

Full Text Available Supercritical fluid extraction (SFE was used in the analysis of bacterial respiratory quinone (RQ, bacterial phospholipid fatty acid (PLFA, and archaeal phospholipid ether lipid (PLEL from anaerobically digested sludge. Bacterial RQ were determined using ultra performance liquid chromatography (UPLC. Determination of bacterial PLFA and archaeal PLEL was simultaneously performed using gas chromatography-mass spectrometry (GC-MS. The effects of pressure, temperature, and modifier concentration on the total amounts of RQ, PLFA, and PLEL were investigated by 23 experiments with five settings chosen for each variable. The optimal extraction conditions that were obtained through a multiple-response optimization included a pressure of 23.6 MPa, temperature of 77.6 °C, and 10.6% (v/v of methanol as the modifier. Thirty nine components of microbial lipid biomarkers were identified in the anaerobically digested sludge. Overall, the SFE method proved to be more effective, rapid, and quantitative for simultaneously extracting bacterial and archaeal lipid biomarkers, compared to conventional organic solvent extraction. This work shows the potential application of SFE as a routine method for the comprehensive analysis of microbial community structures in environmental assessments using the lipid biomarkers profile.

Understanding the degradation of ascorbic acid and glutathione in relation to the levels of oxidative stress biomarkers in broccoli (Brassica oleracea L. italica cv. Bellstar) during storage and mechanical processing.

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Raseetha, Siva; Leong, Sze Ying; Burritt, David John; Oey, Indrawati

2013-06-01

The purpose of this research was to understand the degradation of ascorbic acid and glutathione content in broccoli florets (Brassica oleracea L. italica cv. Bellstar) during prolonged storage and subsequent mechanical processing. The initial content of total ascorbic acid and glutathione in broccoli florets averaged at 5.18 ± 0.23 and 0.70 ± 0.03 μmol/g fresh weight, respectively. Results showed that the content of ascorbic acid and glutathione in broccoli degraded during storage at 23°C, for at least 4.5-fold after 6 days of storage. On each day of storage, broccoli florets were mechanically processed, but the content of total ascorbic acid and glutathione was not significantly affected. When the mechanically processed broccoli florets were further incubated for up to 6h, the amount of ascorbic acid was greatly reduced as compared to glutathione. To obtain an in-depth understanding on the degradation of ascorbic acid and glutathione, the activity of enzymes involved in plant antioxidative system via ascorbate-glutathione cycle, as a response towards oxidative stress that took place during storage was determined in this study. The content of total ascorbic acid and glutathione in broccoli florets before and after mechanical processing were found to decrease concurrently with the activity of ascorbic acid peroxidase and glutathione reductase over the experimental storage duration. Meanwhile, the effect of oxidative stress on the content of ascorbic acid and glutathione was apparent during the 6h of incubation after mechanical processing. This phenomenon was demonstrated by the level of oxidative stress biomarkers examined, in which the formation of lipid peroxides, protein carbonyls and DNA oxidised products was positively associated with the degradation of total ascorbic acid and glutathione. Copyright © 2012 Elsevier Ltd. All rights reserved.

Voltammetric Determination of Tumor Biomarkers for Neuroblastoma (Homovanillic Acid, Vanillylmandelic Acid, and 5-Hydroxyindole-3-acetic Acid) at Screen-printed Carbon Electrodes

Czech Academy of Sciences Publication Activity Database

Makrlíková, Anna; Ktena, E.; Economou, A.; Fischer, J.; Navrátil, Tomáš; Barek, J.; Vyskočil, V.

2017-01-01

Roč. 29, č. 1 (2017), s. 146-153 ISSN 1040-0397 Institutional support: RVO:61388955 Keywords : Homovanillic acid * Vanillylmandelic acid * 5-Hydroxyindole-3-acetic acid Subject RIV: CG - Electrochemistry OBOR OECD: Electrochemistry (dry cells, batteries, fuel cells, corrosion metals, electrolysis) Impact factor: 2.851, year: 2016

Cardiovascular biomarkers in clinical studies of type 2 diabetes

DEFF Research Database (Denmark)

Baldassarre, M P A; Andersen, A; Consoli, A

2018-01-01

biomarkers and 3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the currently best validated biomarkers with special focus on the population of interest (type 2 diabetes). For each individual biomarker, the physiological role, the validation...

Dietary and health biomarkers-time for an update

NARCIS (Netherlands)

Dragsted, L.O.; Gao Qizian,; Praticò, G.; Manach, Claudine; Wishart, D.S.; Scalbert, A.; Feskens, E.J.M.

2017-01-01

In the dietary and health research area, biomarkers are extensively used for multiple purposes. These include biomarkers of dietary intake and nutrient status, biomarkers used to measure the biological effects of specific dietary components, and biomarkers to assess the effects of diet on health.

Evaluating biomarkers for prognostic enrichment of clinical trials.

Science.gov (United States)

Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

2017-12-01

A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

The current status of biomarkers for predicting toxicity

Science.gov (United States)

Campion, Sarah; Aubrecht, Jiri; Boekelheide, Kim; Brewster, David W; Vaidya, Vishal S; Anderson, Linnea; Burt, Deborah; Dere, Edward; Hwang, Kathleen; Pacheco, Sara; Saikumar, Janani; Schomaker, Shelli; Sigman, Mark; Goodsaid, Federico

2013-01-01

Introduction There are significant rates of attrition in drug development. A number of compounds fail to progress past preclinical development due to limited tools that accurately monitor toxicity in preclinical studies and in the clinic. Research has focused on improving tools for the detection of organ-specific toxicity through the identification and characterization of biomarkers of toxicity. Areas covered This article reviews what we know about emerging biomarkers in toxicology, with a focus on the 2012 Northeast Society of Toxicology meeting titled ‘Translational Biomarkers in Toxicology.’ The areas covered in this meeting are summarized and include biomarkers of testicular injury and dysfunction, emerging biomarkers of kidney injury and translation of emerging biomarkers from preclinical species to human populations. The authors also provide a discussion about the biomarker qualification process and possible improvements to this process. Expert opinion There is currently a gap between the scientific work in the development and qualification of novel biomarkers for nonclinical drug safety assessment and how these biomarkers are actually used in drug safety assessment. A clear and efficient path to regulatory acceptance is needed so that breakthroughs in the biomarker toolkit for nonclinical drug safety assessment can be utilized to aid in the drug development process. PMID:23961847

Serotonin Metabolites in the Cerebrospinal Fluid in the Sudden Infant Death Syndrome: In Search of a Biomarker of Risk

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Rognum, Ingvar J.; Tran, Hoa; Haas, Elisabeth A.; Hyland, Keith; Paterson, David S.; Haynes, Robin L.; Broadbelt, Kevin G.; Harty, Brian J.; Mena, Othon; Krous, Henry F.; Kinney, Hannah C.

2015-01-01

Clinical biomarkers are urgently needed in the sudden infant death syndrome (SIDS) to identify living infants at risk because it because it occurs without occurs without clinical warning. Previously, we reported multiple serotonergic (5-HT) abnormalities in nuclei of the medulla oblongata that help mediate protective responses to homeostatic stressors. Here we test the hypothesis that 5-HT-related measures are abnormal in the cerebrospinal fluid (CSF) of SIDS infants compared to autopsy controls, as a first step towards their assessment as diagnostic biomarkers of medullary pathology. Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), the degradative products of 5-HT and dopamine, respectively, were measured by high performance liquid chromatography in 57 SIDS and 29 non-SIDS autopsy cases. Tryptophan (Trp) and tyrosine (Tyr), the substrates of 5-HT and dopamine, respectively, were also measured. There were no significant differences in 5-HIAA, Trp, HVA, or Tyr levels between the SIDS and non-SIDS groups. These data preclude use of 5-HIAA, HVA, Trp or Tyr measurements as CSF biomarkers of 5-HT medullary pathology in infants at risk. They provide, however, important information about monoaminergic measurements in human CSF at autopsy and their developmental profile in infancy that is applicable to multiple pediatric disorders beyond SIDS. PMID:24423636

Analysis of a urinary biomarker panel for obstructive nephropathy and clinical outcomes.

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Yuanyuan Xie

Full Text Available To follow up renal function changes in patients with obstructive nephropathy and to evaluate the predictive value of biomarker panel in renal prognosis.A total of 108 patients with obstructive nephropathy were enrolled in the study; 90 patients completed the follow-up. At multiple time points before and after obstruction resolution, urinary samples were prospectively collected in patients with obstructive nephropathy; the levels of urinary kidney injury molecule-1 (uKIM-1, liver-type fatty acid-binding protein (uL-FABP, and neutrophil gelatinase associated lipocalin (uNGAL were determined by enzyme-linked immunosorbent assay (ELISA. After 1 year of follow-up, the predictive values of biomarker panel for determining the prognosis of obstructive nephropathy were evaluated.uKIM-1 (r = 0.823, uL-FABP (r = 0.670, and uNGAL (r = 0.720 levels were positively correlated with the serum creatinine level (all P96.69 pg/mg creatinine (Cr, a preoperative uL-FABP>154.62 ng/mg Cr, and a 72-h postoperative uL-FABP>99.86 ng/mg Cr were all positively correlated with poor prognosis (all P<0.01.Biomarker panel may be used as a marker for early screening of patients with obstructive nephropathy and for determining poor prognosis.

Assays for urinary biomarkers of oxidatively damaged nucleic acids

DEFF Research Database (Denmark)

Weimann, Allan; Broedbaek, Kasper; Henriksen, Trine

2012-01-01

Abstract The analysis of oxidized nucleic acid metabolites can be performed by a variety of methodologies: liquid chromatography coupled with electrochemical or mass-spectrometry detection, gas chromatography coupled with mass spectrometry, capillary electrophoresis and ELISA (Enzyme-linked immun...

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study.

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Kathleen D Liu

Full Text Available Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood.866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1, neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18, and liver fatty acid binding protein (L-FABP were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit.Median storage was 17.8 months (25-75% IQR 10.6-23.7 for samples from the index hospitalization and 14.6 months (IQR 7.3-20.4 for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%. There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization.There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes.

Biomarkers of Renal Disease and Progression in Patients with Diabetes

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Radovan Hojs

2015-05-01

Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

Novel free-radical mediated lipid peroxidation biomarkers in newborn plasma.

Science.gov (United States)

Sánchez-Illana, Ángel; Thayyil, Sudhin; Montaldo, Paolo; Jenkins, Dorothea; Quintás, Guillermo; Oger, Camille; Galano, Jean-Marie; Vigor, Claire; Durand, Thierry; Vento, Máximo; Kuligowski, Julia

2017-12-15

Oxidative stress derived from perinatal asphyxia appears to be closely linked to neonatal brain damage and lipid peroxidation biomarkers have shown to provide predictive power of oxidative stress related pathologies in situations of hypoxia and reoxygenation in the newborn. The objective of this work was to develop and validate of a comprehensive liquid chromatography tandem mass spectrometry approach for the quantitative profiling of 28 isoprostanoids in newborn plasma samples covering a broad range of lipid peroxidation product classes. The method was developed taking into account the specific requirements for its use in neonatology (i.e. limited sample volumes, straightforward sample processing and high analytical throughput). The method was validated following stringent FDA guidelines and was then applied to the analysis of 150 plasma samples collected from newborns. Information obtained from the quantitative analysis of isoprostanoids was critically compared to that provided by a previously developed approach aiming at the semi-quantitative detection of total parameters of fatty acid derived lipid peroxidation biomarkers. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

International Nuclear Information System (INIS)

Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

2005-01-01

Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

The NINDS Parkinson's disease biomarkers program: The Ninds Parkinson's Disease Biomarkers Program

Energy Technology Data Exchange (ETDEWEB)

Rosenthal, Liana S. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Drake, Daniel [Department of Biostatistics, Columbia University, New York New York USA; Alcalay, Roy N. [Department of Neurology, Columbia University, New York New York USA; Babcock, Debra [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Bowman, F. DuBois [Department of Biostatistics, Columbia University, New York New York USA; Chen-Plotkin, Alice [Department of Neurology, University of Pennsylvania, Philadelphia Pennsylvania USA; Dawson, Ted M. [Department of Neurology, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Solomon H. Snyder Department of Neuroscience, Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore Maryland USA; Dewey, Richard B. [Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas USA; German, Dwight C. [Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas USA; Huang, Xuemei [Department of Neurology, Penn State Hershey Medical Center, Hershey Pennsylvania USA; Landin, Barry [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; McAuliffe, Matthew [Center for Information Technology, National Institutes of Health, Bethesda Maryland USA; Petyuk, Vladislav A. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland Washington USA; Scherzer, Clemens R. [Department of Neurology, Brigham & Women' s Hospital, Harvard Medical School, Cambridge Massachusetts USA; Hillaire-Clarke, Coryse St. [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sieber, Beth-Anne [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Sutherland, Margaret [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA; Tarn, Chi [Coriell Institute for Medical Research, Camden New Jersey USA; West, Andrew [Department of Neurology, University of Alabama at Birmingham, Birmingham USA; Vaillancourt, David [Department of Applied Physiology and Kinesiology, University of Florida, Gainesville Florida USA; Zhang, Jing [Department of Pathology, University of Washington, Seattle Washington USA; Gwinn, Katrina [National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda Maryland USA

2015-10-07

Background: Neuroprotection for Parkinson Disease (PD) remains elusive. Biomarkers hold the promise of removing roadblocks to therapy development. The National Institute of Neurological Disorders and Stroke (NINDS) has therefore established the Parkinson’s Disease Biomarkers Program (PDBP) to promote discovery of biomarkers for use in phase II-III clinical trials in PD. Methods: The PDBP facilitates biomarker development to improve neuroprotective clinical trial design, essential for advancing therapeutics for PD. To date, eleven consortium projects in the PDBP are focused on the development of clinical and laboratory-based PD biomarkers for diagnosis, progression tracking, and/or the prediction of prognosis. Seven of these projects also provide detailed longitudinal data and biospecimens from PD patients and controls, as a resource for all PD researchers. Standardized operating procedures and pooled reference samples have been created in order to allow cross-project comparisons and assessment of batch effects. A web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community for additional biomarker projects. Results: Here we describe the PDBP, highlight standard operating procedures for the collection of biospecimens and data, and provide an interim report with quality control analysis on the first 1082 participants and 1033 samples with quality control analysis collected as of October 2014. Conclusions: By making samples and data available to academics and industry, encouraging the adoption of existing standards, and providing a resource which complements existing programs, the PDBP will accelerate the pace of PD biomarker research, with the goal of improving diagnostic methods and treatment.

Biomarkers of the Dementia

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Mikio Shoji

2011-01-01

Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

Automation on an Open-Access Platform of Alzheimer's Disease Biomarker Immunoassays.

Science.gov (United States)

Gille, Benjamin; Dedeene, Lieselot; Stoops, Erik; Demeyer, Leentje; Francois, Cindy; Lefever, Stefanie; De Schaepdryver, Maxim; Brix, Britta; Vandenberghe, Rik; Tournoy, Jos; Vanderstichele, Hugo; Poesen, Koen

2018-04-01

The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access platforms will facilitate the integration of automation for novel biomarkers, allowing the introduction of the protein profiling concept. A feasibility study was performed on an automated open-access platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid-β (Aβ 1-42 ), Aβ 1-40 , and total tau in CSF. Automated Aβ 1-42 , Aβ 1-40 , and tau immunoassays were performed within predefined acceptance criteria for bias and imprecision. Similar accuracy was obtained for ready-to-use calibrators as for reconstituted lyophilized kit calibrators. When compared with the addition of a standard curve in each test run, the use of a master calibrator curve, determined before and applied to each batch analysis as the standard curve, yielded an acceptable overall bias of -2.6% and -0.9% for Aβ 1-42 and Aβ 1-40 , respectively, with an imprecision profile of 6.2% and 8.4%, respectively. Our findings show that transfer of commercial manual immunoassays to fully automated open-access platforms is feasible, as it performs according to universal acceptance criteria.

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia.

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Yong Tan

Full Text Available Hyperuricemia (HU often progresses to combine with non-alcoholic fatty liver disease (NAFLD in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD, were recruited in this study. The metabolic profiles of all subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0 and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression.

Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

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Yamada, Takashi; Hashimoto, Ryu-Ichiro; Yahata, Noriaki; Ichikawa, Naho; Yoshihara, Yujiro; Okamoto, Yasumasa; Kato, Nobumasa; Takahashi, Hidehiko; Kawato, Mitsuo

2017-10-01

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Biomarkers of therapeutic responses in chronic Chagas disease: state of the art and future perspectives

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Maria-Jesus Pinazo

2015-05-01

Full Text Available The definition of a biomarker provided by the World Health Organization is any substance, structure, or process that can be measured in the body, or its products and influence, or predict the incidence or outcome of disease. Currently, the lack of prognosis and progression markers for chronic Chagas disease has posed limitations for testing new drugs to treat this neglected disease. Several molecules and techniques to detect biomarkers in Trypanosoma cruzi-infected patients have been proposed to assess whether specific treatment with benznidazole or nifurtimox is effective. Isolated proteins or protein groups from different T. cruzi stages and parasite-derived glycoproteins and synthetic neoglycoconjugates have been demonstrated to be useful for this purpose, as have nucleic acid amplification techniques. The amplification of T. cruzi DNA using the real-time polymerase chain reaction method is the leading test for assessing responses to treatment in a short period of time. Biochemical biomarkers have been tested early after specific treatment. Cytokines and surface markers represent promising molecules for the characterisation of host cellular responses, but need to be further assessed.

[Odd- and branched-chain fatty acids in milk fat--characteristic and health properties].

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Adamska, Agata; Rutkowska, Jarosława

2014-08-22

This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat). For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

Diagnostic and prognostic epigenetic biomarkers in cancer.

Science.gov (United States)

Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

2015-01-01

Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

MicroRNA biomarkers in glioblastoma

DEFF Research Database (Denmark)

Hermansen, Simon Kjær; Kristensen, Bjarne Winther

2013-01-01

tissues. Understanding these alterations is key to developing new biomarkers and intelligent treatment strategies. This review presents an overview of current knowledge about miRNA alterations in glioblastoma while focusing on the clinical future of miRNAs as biomarkers and discussing the strengths...

Biomarkers of Dairy Fatty Acids and Risk of Cardiovascular Disease in the Multi-Ethnic Study of Atherosclerosis

NARCIS (Netherlands)

Oliveira Otto, de M.C.; Nettleton, J.A.; Lemaitre, R.N.; Steffen, L.M.; Kromhout, D.; Rich, R.L.; Tsai, M.Y.; Jacobs, D.R.; Mozaffarian, D.

2013-01-01

Background Evidence regarding the role of dairy fat intake in cardiovascular disease (CVD) has been mixed and inconclusive. Most earlier studies have used self-reported measures of dietary intake and focused on relatively racially homogeneous populations. Circulating biomarkers of dairy fat in a

Biomarkers in acute heart failure.

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Mallick, Aditi; Januzzi, James L

2015-06-01

The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

High throughput HPLC-ESI(-)-MS/MS methodology for mercapturic acid metabolites of 1,3-butadiene: Biomarkers of exposure and bioactivation.

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Kotapati, Srikanth; Esades, Amanda; Matter, Brock; Le, Chap; Tretyakova, Natalia

2015-11-05

1,3-Butadiene (BD) is an important industrial and environmental carcinogen present in cigarette smoke, automobile exhaust, and urban air. The major urinary metabolites of BD in humans are 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA), and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutyl mercapturic acid (THBMA), which are formed from the electrophilic metabolites of BD, 3,4-epoxy-1-butene (EB), hydroxymethyl vinyl ketone (HMVK), and 3,4-epoxy-1,2-diol (EBD), respectively. In the present work, a sensitive high-throughput HPLC-ESI(-)-MS/MS method was developed for simultaneous quantification of MHBMA and DHBMA in small volumes of human urine (200 μl). The method employs a 96 well Oasis HLB SPE enrichment step, followed by isotope dilution HPLC-ESI(-)-MS/MS analysis on a triple quadrupole mass spectrometer. The validated method was used to quantify MHBMA and DHBMA in urine of workers from a BD monomer and styrene-butadiene rubber production facility (40 controls and 32 occupationally exposed to BD). Urinary THBMA concentrations were also determined in the same samples. The concentrations of all three BD-mercapturic acids and the metabolic ratio (MHBMA/(MHBMA+DHBMA+THBMA)) were significantly higher in the occupationally exposed group as compared to controls and correlated with BD exposure, with each other, and with BD-hemoglobin biomarkers. This improved high throughput methodology for MHBMA and DHBMA will be useful for future epidemiological studies in smokers and occupationally exposed workers. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Lichen biomarkers upon heating: a Raman spectroscopic study with implications for extra-terrestrial exploration

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Miralles, I.; Capel Ferrón, C.; Hernández, V.; López-Navarrete, J. T.; Jorge-Villar, S. E.

2017-01-01

Lithopanspermia Theory has suggested that life was transferred among planets by meteorites and other rocky bodies. If the planet had an atmosphere, this transfer of life had to survive drastic temperature changes in a very short time in its entry or exit. Only organisms able to endure such a temperature range could colonize a planet from outer space. Many experiments are being carried out by NASA and European Space Agency to understand which organisms were able to survive and how. Among the suite of instruments designed for extraplanetary exploration, particularly for Mars surface exploration, a Raman spectrometer was selected with the main objective of looking for life signals. Among all attributes, Raman spectroscopy is able to identify organic and inorganic compounds, either pure or in admixture, without requiring sample manipulation. In this study, we used Raman spectroscopy to examine the lichen Squamarina lentigera biomarkers. We analyse spectral signature changes after sample heating under different experimental situations, such as (a) laser, (b) analysis accumulations over the same spot and (c) environmental temperature increase. Our goal is to evaluate the capability of Raman spectroscopy to identify unambiguously life markers even if heating has induced spectral changes, reflecting biomolecular transformations. Usnic acid, chlorophyll, carotene and calcium oxalates were identified by the Raman spectra. From our experiments, we have seen that usnic acid, carotene and calcium oxalates (the last two have been suggested to be good biomarkers) respond in a different way to environmental heating. Our main conclusion is that despite their abundance in nature or their inorganic composition the resistance to heat makes some molecules more suitable than others as biomarkers.

Inflammatory biomarkers and cancer

DEFF Research Database (Denmark)

Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

2017-01-01

and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

RECENT ADVANCES IN BIOMARKERS IN SEVERE BURNS.

Science.gov (United States)

Ruiz-Castilla, Mireia; Roca, Oriol; Masclans, Joan R; Barret, Joan P

2016-02-01

The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. In this context, research into biomarkers may play a major role. Biomarkers have traditionally been considered an important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.

The Indian Consensus Document on cardiac biomarker

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I. Satyamurthy

2014-01-01

Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

Biomarkers in DILI: one more step forward

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Mercedes Robles-Díaz

2016-08-01

Full Text Available Despite being relatively rare, drug-induced liver injury (DILI is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in omics technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (for example metabolites, proteins or DNA simultaneously enables the identification of ‘toxicity signatures’, which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review we summarize recent advances in the area of DILI biomarker studies.

Biomarkers for equine joint injury and osteoarthritis.

Science.gov (United States)

McIlwraith, C Wayne; Kawcak, Christopher E; Frisbie, David D; Little, Christopher B; Clegg, Peter D; Peffers, Mandy J; Karsdal, Morten A; Ekman, Stina; Laverty, Sheila; Slayden, Richard A; Sandell, Linda J; Lohmander, L S; Kraus, Virginia B

2018-03-01

We report the results of a symposium aimed at identifying validated biomarkers that can be used to complement clinical observations for diagnosis and prognosis of joint injury leading to equine osteoarthritis (OA). Biomarkers might also predict pre-fracture change that could lead to catastrophic bone failure in equine athletes. The workshop was attended by leading scientists in the fields of equine and human musculoskeletal biomarkers to enable cross-disciplinary exchange and improve knowledge in both. Detailed proceedings with strategic planning was written, added to, edited and referenced to develop this manuscript. The most recent information from work in equine and human osteoarthritic biomarkers was accumulated, including the use of personalized healthcare to stratify OA phenotypes, transcriptome analysis of anterior cruciate ligament (ACL) and meniscal injuries in the human knee. The spectrum of "wet" biomarker assays that are antibody based that have achieved usefulness in both humans and horses, imaging biomarkers and the role they can play in equine and human OA was discussed. Prediction of musculoskeletal injury in the horse remains a challenge, and the potential usefulness of spectroscopy, metabolomics, proteomics, and development of biobanks to classify biomarkers in different stages of equine and human OA were reviewed. The participants concluded that new information and studies in equine musculoskeletal biomarkers have potential translational value for humans and vice versa. OA is equally important in humans and horses, and the welfare issues associated with catastrophic musculoskeletal injury in horses add further emphasis to the need for good validated biomarkers in the horse. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:823-831, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

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Goel, Ajay; Tovar-Camargo, Oscar A; Toden, Shusuke

2016-01-01

Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and a better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called ‘exosomes’, which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

Biology and Biomarkers for Wound Healing

Science.gov (United States)

Lindley, Linsey E.; Stojadinovic, Olivera; Pastar, Irena; Tomic-Canic, Marjana

2016-01-01

Background As the population grows older, the incidence and prevalence of conditions which lead to a predisposition for poor wound healing also increases. Ultimately, this increase in non-healing wounds has led to significant morbidity and mortality with subsequent huge economic ramifications. Therefore, understanding specific molecular mechanisms underlying aberrant wound healing is of great importance. It has, and will continue to be the leading pathway to the discovery of therapeutic targets as well as diagnostic molecular biomarkers. Biomarkers may help identify and stratify subsets of non-healing patients for whom biomarker-guided approaches may aid in healing. Methods A series of literature searches were performed using Medline, PubMed, Cochrane Library, and Internet searches. Results Currently, biomarkers are being identified using biomaterials sourced locally, from human wounds and/or systemically using systematic high-throughput “omics” modalities (genomic, proteomic, lipidomic, metabolomic analysis). In this review we highlight the current status of clinically applicable biomarkers and propose multiple steps in validation and implementation spectrum including those measured in tissue specimens e.g. β-catenin and c-myc, wound fluid e.g. MMP’s and interleukins, swabs e.g. wound microbiota and serum e.g. procalcitonin and MMP’s. Conclusions Identification of numerous potential biomarkers utilizing different avenues of sample collection and molecular approaches is currently underway. A focus on simplicity, and consistent implementation of these biomarkers as well as an emphasis on efficacious follow-up therapeutics is necessary for transition of this technology to clinically feasible point-of-care applications. PMID:27556760

Overview of Biomarkers and Surrogate Endpoints in Drug Development

Directory of Open Access Journals (Sweden)

John A. Wagner

2002-01-01

Full Text Available There are numerous factors that recommend the use of biomarkers in drug development including the ability to provide a rational basis for selection of lead compounds, as an aid in determining or refining mechanism of action or pathophysiology, and the ability to work towards qualification and use of a biomarker as a surrogate endpoint. Examples of biomarkers come from many different means of clinical and laboratory measurement. Total cholesterol is an example of a clinically useful biomarker that was successfully qualified for use as a surrogate endpoint. Biomarkers require validation in most circumstances. Validation of biomarker assays is a necessary component to delivery of high-quality research data necessary for effective use of biomarkers. Qualification is necessary for use of a biomarker as a surrogate endpoint. Putative biomarkers are typically identified because of a relationship to known or hypothetical steps in a pathophysiologic cascade. Biomarker discovery can also be effected by expression profiling experiment using a variety of array technologies and related methods. For example, expression profiling experiments enabled the discovery of adipocyte related complement protein of 30 kD (Acrp30 or adiponectin as a biomarker for in vivo activation of peroxisome proliferator-activated receptors (PPAR γ activity.

Blood-borne biomarkers of mortality risk: systematic review of cohort studies.

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Evelyn Barron

Full Text Available Lifespan and the proportion of older people in the population are increasing, with far reaching consequences for the social, political and economic landscape. Unless accompanied by an increase in health span, increases in age-related diseases will increase the burden on health care resources. Intervention studies to enhance healthy ageing need appropriate outcome measures, such as blood-borne biomarkers, which are easily obtainable, cost-effective, and widely accepted. To date there have been no systematic reviews of blood-borne biomarkers of mortality.To conduct a systematic review to identify available blood-borne biomarkers of mortality that can be used to predict healthy ageing post-retirement.Four databases (Medline, Embase, Scopus, Web of Science were searched. We included prospective cohort studies with a minimum of two years follow up and data available for participants with a mean age of 50 to 75 years at baseline.From a total of 11,555 studies identified in initial searches, 23 fulfilled the inclusion criteria. Fifty-one blood borne biomarkers potentially predictive of mortality risk were identified. In total, 20 biomarkers were associated with mortality risk. Meta-analyses of mortality risk showed significant associations with C-reactive protein (Hazard ratios for all-cause mortality 1.42, p<0.001; Cancer-mortality 1.62, p<0.009; CVD-mortality 1.31, p = 0.033, N Terminal-pro brain natriuretic peptide (Hazard ratios for all-cause mortality 1.43, p<0.001; CHD-mortality 1.58, p<0.001; CVD-mortality 1.67, p<0.001 and white blood cell count (Hazard ratios for all-cause mortality 1.36, p = 0.001. There was also evidence that brain natriuretic peptide, cholesterol fractions, erythrocyte sedimentation rate, fibrinogen, granulocytes, homocysteine, intercellular adhesion molecule-1, neutrophils, osteoprotegerin, procollagen type III aminoterminal peptide, serum uric acid, soluble urokinase plasminogen activator receptor, tissue inhibitor of

Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma

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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.

Three-Dimensionally Functionalized Reverse Phase Glycoprotein Array for Cancer Biomarker Discovery and Validation.

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Pan, Li; Aguilar, Hillary Andaluz; Wang, Linna; Iliuk, Anton; Tao, W Andy

2016-11-30

Glycoproteins have vast structural diversity that plays an important role in many biological processes and have great potential as disease biomarkers. Here, we report a novel functionalized reverse phase protein array (RPPA), termed polymer-based reverse phase glycoprotein array (polyGPA), to capture and profile glycoproteomes specifically, and validate glycoproteins. Nitrocellulose membrane functionalized with globular hydroxyaminodendrimers was used to covalently capture preoxidized glycans on glycoproteins from complex protein samples such as biofluids. The captured glycoproteins were subsequently detected using the same validated antibodies as in RPPA. We demonstrated the outstanding specificity, sensitivity, and quantitative capabilities of polyGPA by capturing and detecting purified as well as endogenous α-1-acid glycoprotein (AGP) in human plasma. We further applied quantitative N-glycoproteomics and the strategy to validate a panel of glycoproteins identified as potential biomarkers for bladder cancer by analyzing urine glycoproteins from bladder cancer patients or matched healthy individuals.

Biomarker monitoring in sports doping control.

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Pottgiesser, Torben; Schumacher, Yorck Olaf

2012-06-01

Biomarker monitoring can be considered a new era in the effort against doping. Opposed to the old concept in doping control of direct detection of a prohibited substance in a biological sample such as urine or blood, the new paradigm allows a personalized longitudinal monitoring of biomarkers that indicate non-physiological responses independently of the used doping technique or substance, and may cause sanctioning of illicit practices. This review presents the development of biomarker monitoring in sports doping control and focuses on the implementation of the Athlete Biological Passport as the current concept of the World Anti Doping Agency for the detection of blood doping (hematological module). The scope of the article extends to the description of novel biomarkers and future concepts of application.

Odd- and branched-chain fatty acids in milk fat – characteristic and health properties

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Agata Adamska

2014-08-01

Full Text Available This review analyzes the current state of knowledge on odd- and branched-chain fatty acids present in milk fat. Special attention is devoted to the characteristic, synthesis in ruminants, factors affecting their content in milk fat and pro-health properties of these compounds. The group of odd- and branched-chain fatty acids includes mainly saturated fatty acids with one or more methyl branches in the iso or anteiso position. These fatty acids are largely derived from ruminal bacteria and they have been transferred to ruminant tissue (milk and meat. For that reason they have been used as biomarkers of rumen fermentation. Odd- and branched-chain fatty acids are exogenous products for humans, and therefore have specific properties. The results of research from recent decades show that odd- and branched-chain fatty acids have anti-cancer activity. Branched-chain fatty acids may reduce the incidence of necrotizing enterocolitis. Additionally, these compounds have a beneficial effect on proper tissue function and on functioning and development of the infant gut, whereas odd-chain fatty acids are considered as biomarkers of milk fat intake by humans. So far, not all the mechanisms of activity of these compounds are known thoroughly. They should be more carefully studied for application of their biological effects in prevention and treatment.

Biomarkers in Prodromal Parkinson Disease: a Qualitative Review.

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Cooper, Christine A; Chahine, Lama M

2016-11-01

Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956-967).

Biomarkers of cancer cachexia.

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Loumaye, Audrey; Thissen, Jean-Paul

2017-12-01

Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Imaging biomarkers as surrogate endpoints for drug development

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Richter, Wolf S.

2006-01-01

The employment of biomarkers (including imaging biomarkers, especially PET) in drug development has gained increasing attention during recent years. This has been partly stimulated by the hope that the integration of biomarkers into drug development programmes may be a means to increase the efficiency and effectiveness of the drug development process by early identification of promising drug candidates - thereby counteracting the rising costs of drug development. More importantly, however, the interest in biomarkers for drug development is the logical consequence of recent advances in biosciences and medicine which are leading to target-specific treatments in the framework of ''personalised medicine''. A considerable proportion of target-specific drugs will show effects in subgroups of patients only. Biomarkers are a means to identify potential responders, or patient subgroups at risk for specific side-effects. Biomarkers are used in early drug development in the context of translational medicine to gain information about the drug's potential in different patient groups and disease states. The information obtained at this stage is mainly important for designing subsequent clinical trials and to identify promising drug candidates. Biomarkers in later phases of clinical development may - if properly validated - serve as surrogate endpoints for clinical outcomes. Regulatory agencies in the EU and the USA have facilitated the use of biomarkers early in the development process. The validation of biomarkers as surrogate endpoints is part of FDA's ''critical path initiative''. (orig.)

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA

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Scherer Gerhard

2017-01-01

Full Text Available An inter-laboratory comparison study on the acrolein biomarker of exposure 3-hydroxypropyl-mercapturic acid (3-HPMA with 12 laboratories from 7 globally distributed countries was performed. The laboratories received coded triplicates of 4 spiked and lyophilized urine samples (LU, 12 samples as well as 5 authentic urine pool samples (PU, 15 samples covering the 3-HPMA concentration range from background (non-smoking to heavy smoking levels for analysis by using their own (in-house analytical method. All laboratories applied liquid chromatography with tandem mass spectrometry (LC-MS/MS, with most of them (10 of 12 using solid phase extraction (SPE as sample work-up procedure. The intra-laboratory variation (indicating repeatability was determined by calculating the standard deviation (sr and the coefficient of variation (CVr of the triplicates, whereas the inter-laboratory variation (indicating reproducibility was determined by calculating the standard deviation between laboratories (sR and the corresponding coefficient of variation (CVR. After removal of outlier samples or laboratories, the mean CVr values for LU and PU test samples ranged from 2.1–3.6% (mean: 2.8% and 2.4–3.7% (mean: 3.3%, respectively, indicating good repeatability for the determination of 3-HPMA in both sample types. CVR for LU and PU test samples ranged from 9.1–31.9% (mean: 18.8% and 13.9–27.0% (mean: 18.5%, respectively, indicating limited reproducibility in 3-HPMA analysis for both sample types. Re-calculation of the PU results by applying an embedded calibration (EC, derived from the reported peak areas for the LU test samples, somewhat improved the CVR values (range: 9.6–28.8%, mean: 16.7%.

Plasma Proteome Biomarkers of Inflammation in School Aged Children in Nepal.

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Sun Eun Lee

Full Text Available Inflammation is a condition stemming from complex host defense and tissue repair mechanisms, often simply characterized by plasma levels of a single acute reactant. We attempted to identify candidate biomarkers of systemic inflammation within the plasma proteome. We applied quantitative proteomics using isobaric mass tags (iTRAQ tandem mass spectrometry to quantify proteins in plasma of 500 Nepalese children 6-8 years of age. We evaluated those that co-vary with inflammation, indexed by α-1-acid glycoprotein (AGP, a conventional biomarker of inflammation in population studies. Among 982 proteins quantified in >10% of samples, 99 were strongly associated with AGP at a family-wise error rate of 0.1%. Magnitude and significance of association varied more among proteins positively (n = 41 than negatively associated (n = 58 with AGP. The former included known positive acute phase proteins including C-reactive protein, serum amyloid A, complement components, protease inhibitors, transport proteins with anti-oxidative activity, and numerous unexpected intracellular signaling molecules. Negatively associated proteins exhibited distinct differences in abundance between secretory hepatic proteins involved in transporting or binding lipids, micronutrients (vitamin A and calcium, growth factors and sex hormones, and proteins of largely extra-hepatic origin involved in the formation and metabolic regulation of extracellular matrix. With the same analytical approach and the significance threshold, seventy-two out of the 99 proteins were commonly associated with CRP, an established biomarker of inflammation, suggesting the validity of the identified proteins. Our findings have revealed a vast plasma proteome within a free-living population of children that comprise functional biomarkers of homeostatic and induced host defense, nutrient metabolism and tissue repair, representing a set of plasma proteins that may be used to assess dynamics and extent of

Storage Time and Urine Biomarker Levels in the ASSESS-AKI Study

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Liu, Kathleen D.; Siew, Edward D.; Reeves, W. Brian; Himmelfarb, Jonathan; Go, Alan S.; Hsu, Chi-yuan; Bennett, Michael R.; Devarajan, Prasad; Ikizler, T. Alp; Kaufman, James S.; Kimmel, Paul L.; Chinchilli, Vernon M.; Parikh, Chirag R.

2016-01-01

Background Although stored urine samples are often used in biomarker studies focused on acute and chronic kidney disease, how storage time impacts biomarker levels is not well understood. Methods 866 subjects enrolled in the NIDDK-sponsored ASsessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study were included. Samples were processed under standard conditions and stored at -70°C until analyzed. Kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and liver fatty acid binding protein (L-FABP) were measured in urine samples collected during the index hospitalization or an outpatient visit 3 months later. Mixed effects models were used to determine the effect of storage time on biomarker levels and stratified by visit. Results Median storage was 17.8 months (25–75% IQR 10.6–23.7) for samples from the index hospitalization and 14.6 months (IQR 7.3–20.4) for outpatient samples. In the mixed effects models, the only significant association between storage time and biomarker concentration was for KIM-1 in outpatient samples, where each month of storage was associated with a 1.7% decrease (95% CI -3% to -0.3%). There was no relationship between storage time and KIM-1 levels in samples from the index hospitalization. Conclusion There was no significant impact of storage time over a median of 18 months on urine KIM-1, NGAL, IL-18 or L-FABP in hospitalized samples; a statistically significant effect towards a decrease over time was noted for KIM-1 in outpatient samples. Additional studies are needed to determine whether longer periods of storage at -70°C systematically impact levels of these analytes. PMID:27788160

More Accurate Oral Cancer Screening with Fewer Salivary Biomarkers

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James Michael Menke

2017-10-01

Full Text Available Signal detection and Bayesian inferential tools were applied to salivary biomarkers to improve screening accuracy and efficiency in detecting oral squamous cell carcinoma (OSCC. Potential cancer biomarkers are identified by significant differences in assay concentrations, receiver operating characteristic areas under the curve (AUCs, sensitivity, and specificity. However, the end goal is to report to individual patients their risk of having disease given positive or negative test results. Likelihood ratios (LRs and Bayes factors (BFs estimate evidential support and compile biomarker information to optimize screening accuracy. In total, 26 of 77 biomarkers were mentioned as having been tested at least twice in 137 studies and published in 16 summary papers through 2014. Studies represented 10 212 OSCC and 25 645 healthy patients. The measure of biomarker and panel information value was number of biomarkers needed to approximate 100% positive predictive value (PPV. As few as 5 biomarkers could achieve nearly 100% PPV for a disease prevalence of 0.2% when biomarkers were ordered from highest to lowest LR. When sequentially interpreting biomarker tests, high specificity was more important than test sensitivity in achieving rapid convergence toward a high PPV. Biomarkers ranked from highest to lowest LR were more informative and easier to interpret than AUC or Youden index. The proposed method should be applied to more recently published biomarker data to test its screening value.

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

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

2017-09-27

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

Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

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Namaste, Sorrel Ml; Aaron, Grant J; Varadhan, Ravi; Peerson, Janet M; Suchdev, Parminder S

2017-07-01

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia. Objectives: The aims of the project were to 1 ) identify factors associated with inflammation, 2 ) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3 ) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA). Design: The BRINDA database inclusion criteria included surveys that 1 ) were conducted after 2004, 2 ) had target groups of PSC, WRA, or both, and 3 ) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis. Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses. Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to

Tissue is alive: New technologies are needed to address the problems of protein biomarker pre-analytical variability.

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Espina, Virginia; Mueller, Claudius; Edmiston, Kirsten; Sciro, Manuela; Petricoin, Emanuel F; Liotta, Lance A

2009-08-01

Instability of tissue protein biomarkers is a critical issue for molecular profiling. Pre-analytical variables during tissue procurement, such as time delays during which the tissue remains stored at room temperature, can cause significant variability and bias in downstream molecular analysis. Living tissue, ex vivo, goes through a defined stage of reactive changes that begin with oxidative, hypoxic and metabolic stress, and culminate in apoptosis. Depending on the delay time ex vivo, and reactive stage, protein biomarkers, such as signal pathway phosphoproteins will be elevated or suppressed in a manner which does not represent the biomarker levels at the time of excision. Proteomic data documenting reactive tissue protein changes post collection indicate the need to recognize and address tissue stability, preservation of post-translational modifications, and preservation of morphologic features for molecular analysis. Based on the analysis of phosphoproteins, one of the most labile tissue protein biomarkers, we set forth tissue procurement guidelines for clinical research. We propose technical solutions for (i) assessing the state of protein analyte preservation and specimen quality via identification of a panel of natural proteins (surrogate stability markers), and (ii) using multi-purpose fixative solution designed to stabilize, preserve and maintain proteins, nucleic acids, and tissue architecture.

Cardiovascular biomarkers and sex: the case for women.

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Daniels, Lori B; Maisel, Alan S

2015-10-01

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

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Iglesia, I; Huybrechts, I; González-Gross, M; Mouratidou, T; Santabárbara, J; Chajès, V; González-Gil, E M; Park, J Y; Bel-Serrat, S; Cuenca-García, M; Castillo, M; Kersting, M; Widhalm, K; De Henauw, S; Sjöström, M; Gottrand, F; Molnár, D; Manios, Y; Kafatos, A; Ferrari, M; Stehle, P; Marcos, A; Sánchez-Muniz, F J; Moreno, L A

2017-01-01

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value DHA (P value acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

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E. N. Aleksandrova

2017-01-01

Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

Associations between omega-3 fatty acids and 25(OH)D and psychological distress among Inuit in Canada.

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Skogli, Hans-Ragnar; Geoffroy, Dominique; Weiler, Hope A; Tell, Grethe S; Kirmayer, Laurence J; Egeland, Grace M

2017-01-01

Inuit in Canada have experienced dietary changes over recent generations, but how this relates to psychological distress has not been investigated. To evaluate how nutritional biomarkers are related to psychological distress. A total of 36 communities in northern Canada participated in the International Polar Year Inuit Health Survey (2007-2008). Of 2796 households, 1901 (68%) participated; 1699 Inuit adults gave blood samples for biomarker analysis and answered the Kessler 6-item psychological distress questionnaire (K6). Biomarkers included n-3 fatty acids and 25-hydroxyvitamin D (25(OH)D). The K6 screens for psychological distress over the last 30 days with six items scored on a 4-point scale. A total score of 13 or more indicates serious psychological distress (SPD). Logistic regression models were used to investigate any associations between SPD and biomarkers while controlling for age, gender, marital status, days spent out on the land, feeling of being alone, income and smoking. The 30-day SPD prevalence was 11.2%, with women below 30 years having the highest and men 50 years and more having the lowest SPD prevalence at 16.1% and 2.6%, respectively. SPD was associated with being female, younger age, not being married or with a common-law partner, spending few days out on the land, feelings of being alone, smoking and low income. Low levels of both 25(OH)D and long-chain n-3 FAs were associated with higher odds for SPD in both unadjusted and adjusted logistic regression models. In this cross-sectional analysis, low levels of 25(OH)D and long-chain n-3 FAs were associated with higher odds ratios for SPD, which highlights the potential impact of traditional foods on mental health and wellbeing. Cultural practices are also important for mental health and it may be that the biomarkers serve as proxies for cultural activities related to food collection, sharing and consumption that increase both biomarker levels and psychological well-being. n-3 FAs: omega-3

Stearoyl-CoA desaturase indexes and n-6/n-3 fatty acids ratio as biomarkers of cardiometabolic risk factors in normal-weight rabbits fed high fat diets.

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Alarcón, Gabriela; Roco, Julieta; Medina, Analia; Van Nieuwenhove, Carina; Medina, Mirta; Jerez, Susana

2016-01-20

Biomarkers for cardiometabolic risk (CMR) factors would be important tools to maximize the effectiveness of dietary interventions to prevent cardiovascular diseases. Thus, the aim of this work was to analyze stearoyl-CoA desaturase (SCD) indexes and n-6/n-3 fatty acids (FA) ratio as biomarkers of CMR induced by feeding rabbits on high fat diets (HFDs). Rabbits were fed either regular diet or 18 % fat in regular diet (HFD) or 1 % cholesterol diet (HD) or diet containing 1 % cholesterol and 18 % fat (HFD-HD) during 6 weeks. Body weights (BW), blood pressure, visceral abdominal fat (VAF) and glucose tolerance test were determined. Total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (TG), fasting glucose (FG), and FA levels from plasma were measured. SCD indexes were calculated as product/precursor ratios of individual FA. BW was similar in all diet groups. HD increased TC, LDL-C, HDL-C, and TG. HFD increased TG, VAF and FG, and decreased HDL-C. The addition of HFD to HD joined to dyslipidemia increased VAF and FG. SCD indexes were increased and n-6/n-3 was unchanged in HD. SCD indexes were reduced and n-6/n-3 FA ratio was increased in HFD and HFD-HD. CMR factors were correlated positively with n-6/n-3 FA ratio. Although VAF had a stronger correlation with n-6/n-3 FA ratio than with SCD indexes, VAF was associated independently to both markers. HFD simulating lipid composition of the average Western-style diet induced experimental rabbit models of normal-weight metabolic syndrome (MS). SCD indexes and n-6/n-3 were modified according to the type of dietary fat. Considering that VAF and CMR factors appear to be stronger associated to n-6/n-3 FA ratio than to SCD indexes, n-6/n-3 FA ratio may be a better biomarker of MS and CMR in normal-weight subjects than SCD indexes.

Insights into particle cycling in the Sargasso Sea from lipid biomarkers in suspended particles: Seasonality and physical forcing

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Pedrosa Pàmies, R.; Conte, M. H.; Weber, J.

2017-12-01

Lipid biomarkers elucidate organic material (OM) sources and cycling within the water column. Biomarker composition and bulk properties (organic carbon (OC), nitrogen (N), OC/N ratio, CaCO3 and stable isotopes) were determined in suspended particles (30-4400 m, 100 mab) collected at Oceanic Flux Program site offshore Bermuda in April/November 2015 and October 2016, three periods of contrasting oceanographic conditions. Key lipid biomarkers were used to evaluate the relative importance of phytoplankton-, bacterial- and zooplankton-OM sources, diagenetic reprocessing, and the impact of upper ocean environmental forcing on the carbon pump. Additionally, we assessed benthic remineralization by comparing particles above and within the nepheloid layer (4400 m). N-fatty acids, n-alcohols and sterols comprise up to 85%, 12% and 7%, respectively, of total extractable lipids. Higher lipid concentrations in April vs November 2015 mirror seasonality in primary production, while change in sterol composition reflect shifts in phytoplankton community structure. In the mesopelagic zone, increased cholesterol/phytosterol ratios and percentages of C16 and C18 n-alcohols, odd-chain and branched n-fatty acids document a transition from algal to animal OM sources as well as bacterial reprocessing of labile OM. The impact of Hurricane Nicole (October 2016) on the mixed layer and subsequent increases in production/flux was evident in higher concentrations as well as greater depth penetration of particulate N and fresh/labile algal biomarkers (e.g. 18:5 ω3 and 22:6 ω3 polyunsaturated fatty acids) in the upper 1000 m. Suspended particles in the nepheloid layer had higher concentrations of OC and N and were more depleted in d13C than particles at 4200 m for all dates. While nepheloid lipid composition was similar for all dates, lipid concentrations in April 2015 (seasonal production peak) and October 2016 (hurricane physical forcing) were higher than in November 2015, consistent with the

Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis

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Aldunate, Muriel; Srbinovski, Daniela; Hearps, Anna C.; Latham, Catherine F.; Ramsland, Paul A.; Gugasyan, Raffi; Cone, Richard A.; Tachedjian, Gilda

2015-01-01

Lactic acid and short chain fatty acids (SCFAs) produced by vaginal microbiota have reported antimicrobial and immune modulatory activities indicating their potential as biomarkers of disease and/or disease susceptibility. In asymptomatic women of reproductive-age the vaginal microbiota is comprised of lactic acid-producing bacteria that are primarily responsible for the production of lactic acid present at ~110 mM and acidifying the vaginal milieu to pH ~3.5. In contrast, bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is characterized by decreased lactic acid-producing microbiota and increased diverse anaerobic bacteria accompanied by an elevated pH>4.5. BV is also characterized by a dramatic loss of lactic acid and greater concentrations of mixed SCFAs including acetate, propionate, butyrate, and succinate. Notably women with lactic acid-producing microbiota have more favorable reproductive and sexual health outcomes compared to women with BV. Regarding the latter, BV is associated with increased susceptibility to sexually transmitted infections (STIs) including HIV. In vitro studies demonstrate that lactic acid produced by vaginal microbiota has microbicidal and virucidal activities that may protect against STIs and endogenous opportunistic bacteria as well as immune modulatory properties that require further characterization with regard to their effects on the vaginal mucosa. In contrast, BV-associated SCFAs have far less antimicrobial activity with the potential to contribute to a pro-inflammatory vaginal environment. Here we review the composition of lactic acid and SCFAs in respective states of eubiosis (non-BV) or dysbiosis (BV), their effects on susceptibility to bacterial/viral STIs and whether they have inherent microbicidal/virucidal and immune modulatory properties. We also explore their potential as biomarkers for the presence and/or increased susceptibility to STIs. PMID:26082720

Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis

Directory of Open Access Journals (Sweden)

Muriel eAldunate

2015-06-01

Full Text Available Lactic acid and short chain fatty acids (SCFAs produced by vaginal microbiota have reported antimicrobial and immune modulatory activities indicating their potential as biomarkers of disease and/or disease susceptibility. In asymptomatic women of reproductive-age the vaginal microbiota is comprised of lactic acid-producing bacteria that are primarily responsible for the production of lactic acid present at ~110 mM and acidifying the vaginal milieu to pH ~3.5. In contrast, bacterial vaginosis (BV, a dysbiosis of the vaginal microbiota, is characterized by decreased lactic acid-producing microbiota and increased diverse anaerobic bacteria accompanied by an elevated pH>4.5. BV is also characterized by a dramatic loss of lactic acid and greater concentrations of mixed SCFAs including acetate, propionate, butyrate and succinate. Notably women with lactic acid-producing microbiota have more favorable reproductive and sexual health outcomes compared to women with BV. Regarding the latter, BV is associated with increased susceptibility to sexually transmitted infections (STIs including HIV. In vitro studies demonstrate that lactic acid produced by vaginal microbiota has microbicidal and virucidal activities that may protect against STIs and endogenous opportunistic bacteria as well as immune modulatory properties that require further characterization with regard to their effects on the vaginal mucosa. In contrast, BV-associated SCFAs have far less antimicrobial activity with the potential to contribute to a pro-inflammatory vaginal environment. Here we review the composition of lactic acid and SCFAs in respective states of eubiosis (non-BV or dysbiosis (BV, their effects on susceptibility to bacterial/viral STIs and whether they have inherent microbicidal/virucidal and immune modulatory properties. We also explore their potential as biomarkers for the presence and/or increased susceptibility to STIs.

Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis.

Science.gov (United States)

Aldunate, Muriel; Srbinovski, Daniela; Hearps, Anna C; Latham, Catherine F; Ramsland, Paul A; Gugasyan, Raffi; Cone, Richard A; Tachedjian, Gilda

2015-01-01

Lactic acid and short chain fatty acids (SCFAs) produced by vaginal microbiota have reported antimicrobial and immune modulatory activities indicating their potential as biomarkers of disease and/or disease susceptibility. In asymptomatic women of reproductive-age the vaginal microbiota is comprised of lactic acid-producing bacteria that are primarily responsible for the production of lactic acid present at ~110 mM and acidifying the vaginal milieu to pH ~3.5. In contrast, bacterial vaginosis (BV), a dysbiosis of the vaginal microbiota, is characterized by decreased lactic acid-producing microbiota and increased diverse anaerobic bacteria accompanied by an elevated pH>4.5. BV is also characterized by a dramatic loss of lactic acid and greater concentrations of mixed SCFAs including acetate, propionate, butyrate, and succinate. Notably women with lactic acid-producing microbiota have more favorable reproductive and sexual health outcomes compared to women with BV. Regarding the latter, BV is associated with increased susceptibility to sexually transmitted infections (STIs) including HIV. In vitro studies demonstrate that lactic acid produced by vaginal microbiota has microbicidal and virucidal activities that may protect against STIs and endogenous opportunistic bacteria as well as immune modulatory properties that require further characterization with regard to their effects on the vaginal mucosa. In contrast, BV-associated SCFAs have far less antimicrobial activity with the potential to contribute to a pro-inflammatory vaginal environment. Here we review the composition of lactic acid and SCFAs in respective states of eubiosis (non-BV) or dysbiosis (BV), their effects on susceptibility to bacterial/viral STIs and whether they have inherent microbicidal/virucidal and immune modulatory properties. We also explore their potential as biomarkers for the presence and/or increased susceptibility to STIs.

Idiopathic recurrent calcium urolithiasis (IRCU: pathophysiology evaluated in light of oxidative metabolism, without and with variation of several biomarkers in fasting urine and plasma - a comparison of stone-free and -bearing male patients, emphasizing mineral, acid-base, blood pressure and protein status*

Directory of Open Access Journals (Sweden)

Schwilie PO

2011-08-01

Full Text Available Abstract Background IRCU is traditionally considered as lifestyle disease (associations with, among others, overweight, obesity, hypertension, type-2 diabetes, arising from excess, in 24 h urine, of calcium (Ca salts (calcium oxalate (CaOx, calcium phosphate (CaPi, supersaturation of, and crystallization in, tubular fluid and urine, causing crystal-induced epithelial cell damage, proteinuria, crystal aggregation and uroliths. Methods Another picture emerges from the present uncontrolled study of 154 male adult IRCU patients (75 stone-bearing (SB and 79 age-matched stone-free (SF, in whom stone-forming and other parameters in fasting urine and plasma were contrasted with five biomarkers (see footnote of oxidative metabolism (OM, without and with variation of markers. Results 1 In SB vs. SF unstratified OM biomarkers were statistically unchanged, but the majority of patients was overweight; despite, in SB vs. SF urine pH, total and non-albumin protein concentration were elevated, fractional urinary uric acid excretion and blood bicarbonate decreased, whereas urine volume, sodium, supersaturation with CaOx and CaPi (as hydroxyapatite were unchanged; 2 upon variation of OM markers (strata below and above median numerous stone parameters differed significant!', among others urine volume, total protein, Ca/Pi ratio, pH, sodium, potassium, plasma Ca/Pi ratio and parathyroid hormone, blood pressure, renal excretion of non-albumin protein and other substances; 3 a significant shift from SF to SB patients occurred with increase of urine pH, decrease of blood bicarbonate, and increase of diastolic blood pressure, whereas increase of plasma uric acid impacted only marginally; 4 in both SF and SB patients a strong curvilinear relationship links a rise of urine Ca/Pi to urine Ca/Pi divided by plasma Ca/Pi, but in SB urine Ca/Pi failed to correlate significantly with urine hydroxyapatite supersaturation; 5 also in SB, plasma Ca/Pi and urinary nitrate were

Biomarkers in T cell therapy clinical trials

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Kalos Michael

2011-08-01

Full Text Available Abstract T cell therapy represents an emerging and promising modality for the treatment of both infectious disease and cancer. Data from recent clinical trials have highlighted the potential for this therapeutic modality to effect potent anti-tumor activity. Biomarkers, operationally defined as biological parameters measured from patients that provide information about treatment impact, play a central role in the development of novel therapeutic agents. In the absence of information about primary clinical endpoints, biomarkers can provide critical insights that allow investigators to guide the clinical development of the candidate product. In the context of cell therapy trials, the definition of biomarkers can be extended to include a description of parameters of the cell product that are important for product bioactivity. This review will focus on biomarker studies as they relate to T cell therapy trials, and more specifically: i. An overview and description of categories and classes of biomarkers that are specifically relevant to T cell therapy trials, and ii. Insights into future directions and challenges for the appropriate development of biomarkers to evaluate both product bioactivity and treatment efficacy of T cell therapy trials.

Lipid Biomarkers and Stable Isotope Signatures of Microbial Mats in Hot Springs of Kamchatka, Russia

Science.gov (United States)

Romanek, C. S.; Mills, G. L.; Jones, M. E.; Paddock, L.; Li, Y.; Zhang, C. L.; Wiegel, J.

2004-12-01

Various hot springs of the Uzon Caldera, Kamchatka, were analyzed for their chemical and stable isotope composition to better understand the relationship(s) between thermophilic microorganisms and the environments in which they live. The springs had water temperatures ranging from 40-90\\deg C and pH ranging from 5.6-5.9. Gases that emanated from the springs were composed predominantly of CO2 (20 to 90%), with lesser amounts of CH4, (Archaea. Results of PLFA showed 16:0 as the most abundant fatty acid (33-44%), which is universal in all living organisms. Other significant biomarkers included 18:1ω (19 to 24%), 18:2ω (5 to 13%), 16:1ω (3 to 12%), and 18:0 (2 to 7%). These biomarkers are characteristic of cyanobacteria, green-sulfur bacteria, and green non-sulfur bacteria, respectively, which are common autotrophic organisms in terrestrial hot springs. On the other hand, biomarkers of heterotrophic bacteria, such as iso- and anteiso-15:0 were low (2-8%), indicating that the bacterial carbon cycle was dominated by autotrophic organisms. Analogous archaeal constituents were present in significant abundance in the ether lipids fraction.

Exploratory metabolomics of biomarker identification for the internet gaming disorder in young Korean males.

Science.gov (United States)

Cho, Yeo Ul; Lee, Deokjong; Lee, Jung-Eun; Kim, Kyoung Heon; Lee, Do Yup; Jung, Young-Chul

2017-07-01

The main aim of the current research is to characterize the molecular dynamics related to internet gaming disorder (IGD) using non-targeted plasma metabolite profiling based on gas-chromatography time-of-flight mass spectrometry (GC-TOF MS). IGD is a psychiatric disorder instigated by excessive and prolonged internet gaming, which shared many pathological symptoms with attention deficit hyperactivity disorder (ADHD). The prevalence of the disorder has been rapidly increased particularly in East Asia countries (5.9% in South Korea) compared to Europe or North America (0.3-1.0% in United States and 1.16% in Germany). Thus we comparably explored the correlation between plasma metabolites and internet addiction severity in IGD patients, and potential biomarker composite in combination with clinical parameters. The systematic metabolite profiling of 54 blood samples (normal user, N=28 and IGD, N=24) identified a total of 104 metabolites out of 1212 metabolic feature, and revealed unique relation of co-linearly regressed set of plasma metabolites (arabitol, myo-inositol, methionine, pyrrole-2-carboxylic acid, and aspartic acid) with internet addiction severity scale (R=0.795). In addition, orthogonal partial least squared discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis identified the potential biomarker cluster that simultaneously discriminated the different types of the psychiatric status. The potential biomarker re-composite was comprehensively evaluated by a receiver operating characteristic (ROC) analysis where the AUCs were 0.890, 0.880, 1.000, and 0.935 for control, IGD, AD and IGD+AD, respectively (N=18, 19, 5, and 10) against the others. This exploratory method may provide robustness of predictive diagnosis in population screening of IGD. The identified metabolic features, the relatedness with clinical parameters, and the putative biochemical linkage will hopefully aid future pathological studies in IGD. Copyright © 2017

The development and applications of biomarkers

International Nuclear Information System (INIS)

Normandy, J.; Peeters, J.

1994-01-01

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community

Biomarkers in psoriasis and psoriatic arthritis.

Science.gov (United States)

Villanova, Federica; Di Meglio, Paola; Nestle, Frank O

2013-04-01

Psoriasis is a common immune-mediated disease of the skin, which associates in 20-30% of patients with psoriatic arthritis (PsA). The immunopathogenesis of both conditions is not fully understood as it is the result of a complex interaction between genetic, environmental and immunological factors. At present there is no cure for psoriasis and there are no specific markers that can accurately predict disease progression and therapeutic response. Therefore, biomarkers for disease prognosis and response to treatment are urgently needed to help clinicians with objective indications to improve patient management and outcomes. Although many efforts have been made to identify psoriasis/PsA biomarkers none of them has yet been translated into routine clinical practice. In this review we summarise the different classes of possible biomarkers explored in psoriasis and PsA so far and discuss novel strategies for biomarker discovery.

The development and applications of biomarkers

Energy Technology Data Exchange (ETDEWEB)

Normandy, J.; Peeters, J. [eds.

1994-04-15

This report is a compilation of submitted abstracts of scientific papers presented at the second Department of Energy-supported workshop on the use and applications of biomarkers held in Santa Fe, New Mexico, from April 26--29, 1994. The abstracts present a synopsis of the latest scientific developments in biomarker research and how these developments meet with the practical needs of the occupational physician as well as the industrial hygienist and the health physicist. In addition to considering the practical applications and potential benefits of this promising technology, the potential ethical and legal ramifications of using biomarkers to monitor workers are discussed. The abstracts further present insights on the present benefits that can be derived from using biomarkers as well as a perspective on what further research is required to fully meet the needs of the medical community.

Biomarkers in spinal cord compression Ethics and perspectives

Directory of Open Access Journals (Sweden)

Iencean A.St.

2016-09-01

Full Text Available The phosphorylated form of the high-molecular-weight neurofilament subunit NF-H (pNF-H in serum or in cerebro-spinal fluid (CSF is a specific lesional biomarker for spinal cord injury. The lesional biomarkers and the reaction biomarkers are both presented after several hours post-injury. The specific predictive patterns of lesional biomarkers could be used to aid clinicians with making a diagnosis and establishing a prognosis, and evaluating therapeutic interventions. Diagnosis, prognosis, and treatment guidance based on biomarker used as a predictive indicator can determine ethical difficulties by differentiated therapies in patients with spinal cord compression. At this point based on studies until today we cannot take a decision based on biomarker limiting the treatment of neurological recovery in patients with complete spinal cord injury because we do not know the complexity of the biological response to spinal cord compression.

Identifying biomarkers for asthma diagnosis using targeted metabolomics approaches.

Science.gov (United States)

Checkley, William; Deza, Maria P; Klawitter, Jost; Romero, Karina M; Klawitter, Jelena; Pollard, Suzanne L; Wise, Robert A; Christians, Uwe; Hansel, Nadia N

2016-12-01

The diagnosis of asthma in children is challenging and relies on a combination of clinical factors and biomarkers including methacholine challenge, lung function, bronchodilator responsiveness, and presence of airway inflammation. No single test is diagnostic. We sought to identify a pattern of inflammatory biomarkers that was unique to asthma using a targeted metabolomics approach combined with data science methods. We conducted a nested case-control study of 100 children living in a peri-urban community in Lima, Peru. We defined cases as children with current asthma, and controls as children with no prior history of asthma and normal lung function. We further categorized enrollment following a factorial design to enroll equal numbers of children as either overweight or not. We obtained a fasting venous blood sample to characterize a comprehensive panel of targeted markers using a metabolomics approach based on high performance liquid chromatography-mass spectrometry. A statistical comparison of targeted metabolites between children with asthma (n = 50) and healthy controls (n = 49) revealed distinct patterns in relative concentrations of several metabolites: children with asthma had approximately 40-50% lower relative concentrations of ascorbic acid, 2-isopropylmalic acid, shikimate-3-phosphate, and 6-phospho-d-gluconate when compared to children without asthma, and 70% lower relative concentrations of reduced glutathione (all p  13 077 normalized counts/second and betaine ≤ 16 47 121 normalized counts/second). By using a metabolomics approach applied to serum, we were able to discriminate between children with and without asthma by revealing different metabolic patterns. These results suggest that serum metabolomics may represent a diagnostic tool for asthma and may be helpful for distinguishing asthma phenotypes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers of intermediate endpoints in environmental and occupational health

DEFF Research Database (Denmark)

Knudsen, Lisbeth E; Hansen, Ase M

2007-01-01

The use of biomarkers in environmental and occupational health is increasing due to increasing demands on information about health risks from unfavourable exposures. Biomarkers provide information about individual loads. Biomarkers of intermediate endpoints benefit in comparison with biomarkers...... of exposure from the fact that they are closer to the adverse outcome in the pathway from exposure to health effects and may provide powerful information for intervention. Some biomarkers are specific, e.g., DNA and protein adducts, while others are unspecific like the cytogenetic biomarkers of chromosomal...... health effect from the result of the measurement has been performed for the cytogenetic biomarkers showing a predictive value of high levels of CA and increased risk of cancer. The use of CA in future studies is, however, limited by the laborious and sensitive procedure of the test and lack of trained...

A comparative study of biological and metabolic biomarkers between healthy individuals and patients with acne vulgaris: A cross-sectional study protocol.

Science.gov (United States)

Kim, Kyuseok; Ha, Injin; Kim, Eunok; Kim, Kyunglee

2017-11-01

Acne is a multifactorial dermatosis, which is influenced not only by hormones but also by the biochemical relationship between them and the pilosebaceous unit. Inflammatory cytokines, chemokines, active oxygen, and zinc are known to be associated with the development of acne. Further, steroid metabolism is known as one of the important factors related to sebum secretion and comedone formation in acne. However, there is a lack of studies comparing these human biomarkers between healthy individuals and patients with acne. In particular, no study has investigated the relationship between human biomarkers and patterns of acne yet.The purpose of this study is to investigate diagnostic human biomarkers in acne by comparing the biological and metabolic biomarkers between healthy individuals and patients with acne and identify the relationship between human biomarkers and patterns of acne.This study is a protocol for a cross-sectional study. Forty healthy participants and 60 patients with acne will be recruited at 1 center. We will collect their blood samples and analyze the molecular biological and metabolic biomarkers (cytokines, chemokines, reactive oxygen species, corticotropin-releasing hormone, zinc, amino acid, 1-carbon metabolite, lipid metabolite, etc.). Further, we will administer questionnaires regarding their diet, sleep, stress, and other factors relating to acne and measure their skin elasticity.The study protocol was approved by the Institutional Review Board of Oriental Medical Hospital at Kyung Hee Medical Center (KOMCIRB-161118-HR-062). Written informed consent will be obtained from all the participants. The trial was registered in the Clinical Research Information Service, Republic of Korea: KCT0002212.This trial will provide evidence regarding diagnostic human biomarkers in acne and the relationship between the human biomarkers and patterns of acne.

Biomarkers of fibrosis and impaired liver function in chronic hepatitis C: how well do they predict clinical outcomes?

DEFF Research Database (Denmark)

Peters, L.; Rockstroh, J.K.

2010-01-01

PURPOSE OF REVIEW: To review the recent literature on the prognostic value of biomarkers of liver fibrosis and impaired liver function in patients with chronic hepatitis C with or without HIV coinfection. RECENT FINDINGS: A combination of standard blood tests seems to be useful in identifying...... levels of the fibrosis marker hyaluronic acid are a strong predictor of clinical complications. A smaller study found hyaluronic acid and two other fibrosis tests, aspartate aminotransferase-to-platelet ratio index (APRI) and Fib-4, to be independent predictors of mortality when included in models...

Effect of environmental conditions on the fatty acid fingerprint of microbial communities

Science.gov (United States)

Biryukov, Mikhail; Dippold, Michaela; Kuzyakov, Yakov

2014-05-01

Lipid biomarkers, especially phospholipids, are routinely used to characterize microbial community structure in environmental samples. Interpretations of these fingerprints mainly depend on rare results of pure cultures which were cultivated under standardized batch conditions. However, membrane lipids (e.g. phopholipid biomarker) build up the interface between microorganisms and their environment and consequently are prone to be adapted according to the environmental conditions. We cultivated several bacteria, isolated from soil (gram-positive and gram-negative) under various conditions e.g. C supply and temperature regimes. Effect of growth conditions on phospholipids fatty acid (PLFA) as well as neutral lipid fatty acids (NLFA) and glycolipid fatty acids (GLFA) was investigated by conventional method of extraction and derivatization, followed by assessments with gas chromatography mass spectrometry (GC-MS). In addition, phospholipids were measured as intact molecules by ultra high performance liquid chromatography - quadrupole - time of flight mass spectrometer (UHPLC-Q-ToF) to further assess the composition of headgroups with fatty acids residues and their response on changing environmental conditions. PLFA fingerprints revealed a strong effect of growth stage, C supply and temperature e.g. decrease of temperature increased the amount of branched and/or unsaturated fatty acids to maintain the membrane fluidity. This strongly changes the ratio of specific to unspecific fatty acids depending on environmental conditions. Therefore, amounts of specific fatty acids cannot be used to assess biomass of a functional microbial group in soil. Intracellular neutral lipids depended less on environmental conditions reflecting a more stable biomarker group but also showed less specific fatty acids then PLFA. Therefore, combination of several lipid classes is suggested as more powerful tool to assess amounts and functionality of environmental microbial communities. Further

CBD: a biomarker database for colorectal cancer.

Science.gov (United States)

Zhang, Xueli; Sun, Xiao-Feng; Cao, Yang; Ye, Benchen; Peng, Qiliang; Liu, Xingyun; Shen, Bairong; Zhang, Hong

2018-01-01

Colorectal cancer (CRC) biomarker database (CBD) was established based on 870 identified CRC biomarkers and their relevant information from 1115 original articles in PubMed published from 1986 to 2017. In this version of the CBD, CRC biomarker data were collected, sorted, displayed and analysed. The CBD with the credible contents as a powerful and time-saving tool provide more comprehensive and accurate information for further CRC biomarker research. The CBD was constructed under MySQL server. HTML, PHP and JavaScript languages have been used to implement the web interface. The Apache was selected as HTTP server. All of these web operations were implemented under the Windows system. The CBD could provide to users the multiple individual biomarker information and categorized into the biological category, source and application of biomarkers; the experiment methods, results, authors and publication resources; the research region, the average age of cohort, gender, race, the number of tumours, tumour location and stage. We only collect data from the articles with clear and credible results to prove the biomarkers are useful in the diagnosis, treatment or prognosis of CRC. The CBD can also provide a professional platform to researchers who are interested in CRC research to communicate, exchange their research ideas and further design high-quality research in CRC. They can submit their new findings to our database via the submission page and communicate with us in the CBD.Database URL: http://sysbio.suda.edu.cn/CBD/.

Emerging Concepts and Methodologies in Cancer Biomarker Discovery.

Science.gov (United States)

Lu, Meixia; Zhang, Jinxiang; Zhang, Lanjing

2017-01-01

Cancer biomarker discovery is a critical part of cancer prevention and treatment. Despite the decades of effort, only a small number of cancer biomarkers have been identified for and validated in clinical settings. Conceptual and methodological breakthroughs may help accelerate the discovery of additional cancer biomarkers, particularly their use for diagnostics. In this review, we have attempted to review the emerging concepts in cancer biomarker discovery, including real-world evidence, open access data, and data paucity in rare or uncommon cancers. We have also summarized the recent methodological progress in cancer biomarker discovery, such as high-throughput sequencing, liquid biopsy, big data, artificial intelligence (AI), and deep learning and neural networks. Much attention has been given to the methodological details and comparison of the methodologies. Notably, these concepts and methodologies interact with each other and will likely lead to synergistic effects when carefully combined. Newer, more innovative concepts and methodologies are emerging as the current emerging ones became mainstream and widely applied to the field. Some future challenges are also discussed. This review contributes to the development of future theoretical frameworks and technologies in cancer biomarker discovery and will contribute to the discovery of more useful cancer biomarkers.

Effect of consumption of tomato juice enriched with n-3 polyunsaturated fatty acids on the lipid profile, antioxidant biomarker status, and cardiovascular disease risk in healthy women.

Science.gov (United States)

García-Alonso, F J; Jorge-Vidal, V; Ros, G; Periago, M J

2012-06-01

We compared the effects of consumption of n-3 polyunsaturated fatty acids (PUFA)-enriched tomato juice versus plain tomato juice on the serum lipid profile and levels of biomarkers related to antioxidant status and cardiovascular disease (CVD) risk in women. Eighteen healthy women participated in a 2-week intervention trial involving the daily intake of 500 mL of n-3 PUFA-enriched juice (n = 11) or plain tomato juice (n = 7). Each serving of enriched juice provided 250 mg of eicosapentaenoic acid (EPA) plus docosahexanoic acid (DHA). Both juices provided natural antioxidant compounds such as phenolics (181 mg) and lycopene (26.5 mg). Intervention with the enriched juice had no effect on the lipid profile, and serum levels of triglycerides and cholesterol (total, LDL, and HDL) remained unchanged. The serum antioxidant status improved following juice intake, as revealed by an increase in total antioxidant capacity and a slight decrease in lipid peroxidation. The serum levels of homocysteine, a cardiovascular risk factor, decreased following n-3 PUFA-enriched juice consumption. A decrease in vascular adhesion molecule 1 (VCAM-1) levels was also noted after intake of either plain or enriched tomato juice, whereas intercellular adhesion molecule 1 (ICAM-1) levels only decreased following intake of the enriched juice. Overall, stronger positive amelioration of CVD risk factors was observed following the intake of n-3 PUFA-enriched juice than after plain tomato juice consumption, which suggested a possible synergistic action between n-3 PUFAs and tomato antioxidants.

Application of a new procedure for liquid chromatography/mass spectrometry profiling of plasma amino acid-related metabolites and untargeted shotgun proteomics to identify mechanisms and biomarkers of calcific aortic stenosis.

Science.gov (United States)

Olkowicz, Mariola; Debski, Janusz; Jablonska, Patrycja; Dadlez, Michal; Smolenski, Ryszard T

2017-09-29

Calcific aortic valve stenosis (CAS) increasingly affects our ageing population, but the mechanisms of the disease and its biomarkers are not well established. Recently, plasma amino acid-related metabolite (AA) profiling has attracted attention in studies on pathology and development of biomarkers of cardiovascular diseases, but has not been studied in CAS. To evaluate the potential relationship between CAS and AA metabolome, a new ion-pairing reversed-phase liquid chromatography-tandem mass spectrometry (IP-RPLC-MS/MS) method has been developed and validated for simultaneous determination of 43 AAs in plasma of stenotic patients and age-matched control subjects. Furthermore, untargeted mass spectrometry-based proteomic analysis and confirmatory ELISA assays were performed. The method developed offered high accuracy (intra-assay imprecision averaged 4.4% for all compounds) and sensitivity (LOQ within 0.01-0.5μM). We found that 22 AAs and three AA ratios significantly changed in the CAS group as compared to control. The most pronounced differences were observed in urea cycle-related AAs and branched-chain AA (BCAA)-related AAs. The contents of asymmetric dimethylarginine (ADMA) and its monomethylated derivative (NMMA) were increased by 30-64% with CAS. The arginine/ADMA and Fischer's ratios as well as arginine, homoarginine, ADMA, symmetric dimethylarginine, hydroxyproline, betaine and 3-methylhistidine correlated with cardiac function-related parameters and concomitant systemic factors in the CAS patients. The results of proteomic analysis were consistent with involvement of inflammation, lipid abnormalities, hemostasis and extracellular matrix remodeling in CAS. In conclusion, changes in plasma AA profile and protein pattern that we identified in CAS provide information relevant to pathomechanisms and may deliver new biomarkers of the disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomarkers of Aging: From Function to Molecular Biology

Directory of Open Access Journals (Sweden)

Karl-Heinz Wagner

2016-06-01

Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

Methane seepage intensities traced by biomarker patterns in authigenic carbonates from the South China Sea

Science.gov (United States)

Guan, H.; Feng, D.

2015-12-01

Authigenic carbonate rocks from an active seep (Site F) at 1120 m water depth of the South China Sea (SCS) were studied using mineralogical and lipid biomarker analyses. Carbonate mineral compositions, in specific samples, were predominantly aragonite, high-Mg calcite (HMC), or a mixture of both. Abundant 13C-depleted lipid biomarkers (various isoprenoids) diagnostic for archaea provide evidence that anaerobic oxidation of methane (AOM) mediated by anaerobic methane oxidizing archaea (ANME) and their bacterial partners is the major process leading to formation of the carbonates. Nearly a pure suite of AOM biomarkers was preserved in aragonitic carbonate in which predominant consortia were most likely ANME-2/Desulfosarcina & Desulfococcus (DSS) assemblages and a mixture of ANME-2/DSS and ANME-1/DSS consortia in the mixed mineral sample, the predominant consortia are in good accordance with the point that the relative higher methane seepage intensity favors the precipitation of aragonite over HMC. In contrast, the completely different biomarker patterns in HMC sample were mainly composed terrestrial organic matter and marine Thaumarchaea, which most likely originally within sediments accompanied with high organic matter input and low methane supply. This environment is known to be favored for archaea of ANME-1 and precipitation of HMC. High concentrations of 13C-depleted hopanoids, including diplopterol, hopanoic acids and hopanols were observed in the aragonite sample that may be sourced by the intermittent presence of oxic conditions in an overall anoxic condition, which was possibly induced by changing seepage intensities.

Biomarkers of PTSD: military applications and considerations

OpenAIRE

Amy Lehrner; Rachel Yehuda

2014-01-01

Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

WONOEP appraisal: Biomarkers of epilepsy-associated comorbidities.

Science.gov (United States)

Ravizza, Teresa; Onat, Filiz Y; Brooks-Kayal, Amy R; Depaulis, Antoine; Galanopoulou, Aristea S; Mazarati, Andrey; Numis, Adam L; Sankar, Raman; Friedman, Alon

2017-03-01

Neurologic and psychiatric comorbidities are common in patients with epilepsy. Diagnostic, predictive, and pharmacodynamic biomarkers of such comorbidities do not exist. They may share pathogenetic mechanisms with epileptogenesis/ictogenesis, and as such are an unmet clinical need. The objectives of the subgroup on biomarkers of comorbidities at the XIII Workshop on the Neurobiology of Epilepsy (WONOEP) were to present the state-of-the-art recent research findings in the field that highlighting potential biomarkers for comorbidities in epilepsy. We review recent progress in the field, including molecular, imaging, and genetic biomarkers of comorbidities as discussed during the WONOEP meeting on August 31-September 4, 2015, in Heybeliada Island (Istanbul, Turkey). We further highlight new directions and concepts from studies on comorbidities and potential new biomarkers for the prediction, diagnosis, and treatment of epilepsy-associated comorbidities. The activation of various molecular signaling pathways such as the "Janus Kinase/Signal Transducer and Activator of Transcription," "mammalian Target of Rapamycin," and oxidative stress have been shown to correlate with the presence and severity of subsequent cognitive abnormalities. Furthermore, dysfunction in serotonergic transmission, hyperactivity of the hypothalamic-pituitary-adrenocortical axis, the role of the inflammatory cytokines, and the contributions of genetic factors have all recently been regarded as relevant for understanding epilepsy-associated depression and cognitive deficits. Recent evidence supports the utility of imaging studies as potential biomarkers. The role of such biomarker may be far beyond the diagnosis of comorbidities, as accumulating clinical data indicate that comorbidities can predict epilepsy outcomes. Future research is required to reveal whether molecular changes in specific signaling pathways or advanced imaging techniques could be detected in the clinical settings and correlate

Proteomic Biomarkers for Spontaneous Preterm Birth

DEFF Research Database (Denmark)

Kacerovsky, Marian; Lenco, Juraj; Musilova, Ivana

2014-01-01

This review aimed to identify, synthesize, and analyze the findings of studies on proteomic biomarkers for spontaneous preterm birth (PTB). Three electronic databases (Medline, Embase, and Scopus) were searched for studies in any language reporting the use of proteomic biomarkers for PTB published...

Imaging biomarker roadmap for cancer studies

NARCIS (Netherlands)

O'Connor, James P. B.; Aboagye, Eric O.; Adams, Judith E.; Aerts, Hugo J. W. L.; Barrington, Sally F.; Beer, Ambros J.; Boellaard, Ronald; Bohndiek, Sarah E.; Brady, Michael; Brown, Gina; Buckley, David L.; Chenevert, Thomas L.; Clarke, Laurence P.; Collette, Sandra; Cook, Gary J.; Desouza, Nandita M.; Dickson, John C.; Dive, Caroline; Evelhoch, Jeffrey L.; Faivre-Finn, Corinne; Gallagher, Ferdia A.; Gilbert, Fiona J.; Gillies, Robert J.; Goh, Vicky; Griffiths, J. R.; Groves, Ashley M.; Halligan, Steve; Harris, Adrian L.; Hawkes, David J.; Hoekstra, Otto S.; Huang, Erich P.; Hutton, Brian F.; Jackson, Edward F.; Jayson, Gordon C.; Jones, Andrew; Koh, Dow-Mu; Lacombe, Denis; Lambin, Philippe; Lassau, Nathalie; Leach, Martin O.; Lee, Ting-Yim; Leen, Edward L.; Lewis, Jason S.; Liu, Yan; Lythgoe, Mark F.; Manoharan, Prakash; Maxwell, Ross J.; Miles, Kenneth A.; Morgan, Bruno; Morris, Steve; Ng, Tony; Padhani, Anwar R.; Parker, Geoff J. M.; Partridge, Mike; Pathak, Arvind P.; Peet, Andrew C.; Punwani, Shonit; Reynolds, Andrew R.; Robinson, Simon P.; Shankar, Lalitha K.; Sharma, Ricky A.; Soloviev, Dmitry; Stroobants, Sigrid G.; Sullivan, Daniel C.; Taylor, Stuart A.; Tofts, Paul S.; Tozer, Gillian M.; van Herk, Marcel B.; Walker-Samuel, Simon; Wason, James; Williams, Kaye J.; Workman, Paul; Yankeelov, Thomas E.; Brindle, Kevin M.; McShane, Lisa M.; Jackson, Alan; Waterton, John C.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and

Evidence from in vivo 31-phosphorus magnetic resonance spectroscopy phosphodiesters that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans

Directory of Open Access Journals (Sweden)

Hamilton Gavin

2008-04-01

Full Text Available Abstract Background This study tested the hypothesis that exhaled ethane is a biomarker of cerebral n-3 polyunsaturated fatty acid peroxidation in humans. Ethane is released specifically following peroxidation of n-3 polyunsaturated fatty acids. We reasoned that the cerebral source of ethane would be the docosahexaenoic acid component of membrane phospholipids. Breakdown of the latter also releases phosphorylated polar head groups, giving rise to glycerophosphorylcholine and glycerophosphorylethanolamine, which can be measured from the 31-phosphorus neurospectroscopy phosphodiester peak. Schizophrenia patients were chosen because of evidence of increased free radical-mediated damage and cerebral lipid peroxidation in this disorder. Methods Samples of alveolar air were obtained from eight patients and ethane was analyzed and quantified by gas chromatography and mass spectrometry (m/z = 30. Cerebral 31-phosphorus spectra were obtained from the same patients at a magnetic field strength of 1.5 T using an image-selected in vivo spectroscopy sequence (TR = 10 s; 64 signal averages localized on a 70 × 70 × 70 mm3 voxel. The quantification of the 31-phosphorus signals using prior knowledge was carried out in the temporal domain after truncating the first 1.92 ms of the signal to remove the broad component present in the 31-phosphorus spectra. Results The ethane and phosphodiester levels, expressed as a percentage of the total 31-phosphorus signal, were positively and significantly correlated (rs = 0.714, p Conclusion Our results support the hypothesis that the measurement of exhaled ethane levels indexes cerebral n-3 lipid peroxidation. From a practical viewpoint, if human cerebral n-3 polyunsaturated fatty acid catabolism can be measured by ethane in expired breath, this would be more convenient than determining the area of the 31-phosphorus neurospectroscopy phosphodiester peak.

Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

Science.gov (United States)

Freund Levi, Y; Vedin, I; Cederholm, T; Basun, H; Faxén Irving, G; Eriksdotter, M; Hjorth, E; Schultzberg, M; Vessby, B; Wahlund, L-O; Salem, N; Palmblad, J

2014-04-01

Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

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Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

Novel biomarkers for prediabetes, diabetes, and associated complications

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Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

2017-01-01

The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

Quantification of biopharmaceuticals and biomarkers in complex biological matrices: a comparison of liquid chromatography coupled to tandem mass spectrometry and ligand binding assays

NARCIS (Netherlands)

Bults, Peter; van de Merbel, Nico C; Bischoff, Rainer

2015-01-01

The quantification of proteins (biopharmaceuticals or biomarkers) in complex biological samples such as blood plasma requires exquisite sensitivity and selectivity, as all biological matrices contain myriads of proteins that are all made of the same 20 proteinogenic amino acids, notwithstanding

The serotonin system in autism spectrum disorder: from biomarker to animal models

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Muller, Christopher L.; Anacker, Allison M.J.; Veenstra-VanderWeele, Jeremy

2015-01-01

Elevated whole blood serotonin, or hyperserotonemia, was the first biomarker identified in autism spectrum disorder (ASD) and is present in more than 25% of affected children. The serotonin system is a logical candidate for involvement in ASD due to its pleiotropic role across multiple brain systems both dynamically and across development. Tantalizing clues connect this peripheral biomarker with changes in brain and behavior in ASD, but the contribution of the serotonin system to ASD pathophysiology remains incompletely understood. Studies of whole blood serotonin levels in ASD and in a large founder population indicate greater heritability than for the disorder itself and suggest an association with recurrence risk. Emerging data from both neuroimaging and postmortem samples also indicate changes in the brain serotonin system in ASD. Genetic linkage and association studies of both whole blood serotonin levels and of ASD risk point to the chromosomal region containing the serotonin transporter (SERT) gene in males but not in females. In ASD families with evidence of linkage to this region, multiple rare SERT amino acid variants lead to a convergent increase in serotonin uptake in cell models. A knock-in mouse model of one of these variants, SERT Gly56Ala, recapitulates the hyperserotonemia biomarker and shows increased brain serotonin clearance, increased serotonin receptor sensitivity, and altered social, communication, and repetitive behaviors. Data from other rodent models also suggest an important role for the serotonin system in social behavior, in cognitive flexibility, and in sensory development. Recent work indicates that reciprocal interactions between serotonin and other systems, such as oxytocin, may be particularly important for social behavior. Collectively, these data point to the serotonin system as a prime candidate for treatment development in a subgroup of children defined by a robust, heritable biomarker. PMID:26577932

Biomarkers: Delivering on the expectation of molecularly driven, quantitative health.

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Wilson, Jennifer L; Altman, Russ B

2018-02-01

Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health. Here we review themes of biomarker discovery, current implementations of biomarkers for precision health, and future opportunities and challenges for biomarker discovery. Impact statement Precision medicine evolved because of the understanding that human disease is molecularly driven and is highly variable across patients. This understanding has made biomarkers, a diverse class of biological measurements, more relevant for disease diagnosis, monitoring, and selection of treatment strategy. Biomarkers' impact on precision medicine can be seen in cancer, pharmacogenomics, and safety. The successes in these cases suggest many more applications for biomarkers and a greater impact for precision medicine across the spectrum of human disease. The authors assess the status of biomarker-guided medical practice by analyzing themes for biomarker discovery, reviewing the impact of these markers in the clinic, and highlight future and ongoing challenges for biomarker discovery. This work is timely and relevant, as the molecular, quantitative approach of precision medicine is spreading to many disease indications.

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

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Betensky, Rebecca A.; Emerson, Sarah C.; Bonventre, Joseph V.

2012-01-01

Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies. PMID:22021710

Biomarkers in cancer screening: a public health perspective.

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Srivastava, Sudhir; Gopal-Srivastava, Rashmi

2002-08-01

The last three decades have witnessed a rapid advancement and diffusion of technology in health services. Technological innovations have given health service providers the means to diagnose and treat an increasing number of illnesses, including cancer. In this effort, research on biomarkers for cancer detection and risk assessment has taken a center stage in our effort to reduce cancer deaths. For the first time, scientists have the technologies to decipher and understand these biomarkers and to apply them to earlier cancer detection. By identifying people at high risk of developing cancer, it would be possible to develop intervention efforts on prevention rather than treatment. Once fully developed and validated, then the regular clinical use of biomarkers in early detection and risk assessment will meet nationally recognized health care needs: detection of cancer at its earliest stage. The dramatic rise in health care costs in the past three decades is partly related to the proliferation of new technologies. More recent analysis indicates that technological change, such as new procedures, products and capabilities, is the primary explanation of the historical increase in expenditure. Biomarkers are the new entrants in this competing environment. Biomarkers are considered as a competing, halfway or add-on technology. Technology such as laboratory tests of biomarkers will cost less compared with computed tomography (CT) scans and other radiographs. However, biomarkers for earlier detection and risk assessment have not achieved the level of confidence required for clinical applications. This paper discusses some issues related to biomarker development, validation and quality assurance. Some data on the trends of diagnostic technologies, proteomics and genomics are presented and discussed in terms of the market share. Eventually, the use of biomarkers in health care could reduce cost by providing noninvasive, sensitive and reliable assays at a fraction of the cost of

Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids

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Background:N-3 fatty acids are associated with favorable, and obesity with unfavorable, concentrations of chronic disease risk biomarkers.Objective:We examined whether high eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intakes, measured as percentages of total red blood cell (RBC) fatty acid...

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

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Huang, Joanne H.; Berkovitch, Shaunna S.; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M.; Clish, Clary B.; Karmacharya, Rakesh

2016-01-01

Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder. PMID:27606323

Advances in Biomarkers in Critical Ill Polytrauma Patients.

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Papurica, Marius; Rogobete, Alexandru F; Sandesc, Dorel; Dumache, Raluca; Cradigati, Carmen A; Sarandan, Mirela; Nartita, Radu; Popovici, Sonia E; Bedreag, Ovidiu H

2016-01-01

The complexity of the cases of critically ill polytrauma patients is given by both the primary, as well as the secondary, post-traumatic injuries. The severe injuries of organ systems, the major biochemical and physiological disequilibrium, and the molecular chaos lead to a high rate of morbidity and mortality in this type of patient. The 'gold goal' in the intensive therapy of such patients resides in the continuous evaluation and monitoring of their clinical status. Moreover, optimizing the therapy based on the expression of certain biomarkers with high specificity and sensitivity is extremely important because of the clinical course of the critically ill polytrauma patient. In this paper we wish to summarize the recent studies of biomarkers useful for the intensive care unit (ICU) physician. For this study the available literature on specific databases such as PubMed and Scopus was thoroughly analyzed. Each article was carefully reviewed and useful information for this study extracted. The keywords used to select the relevant articles were "sepsis biomarker", "traumatic brain injury biomarker" "spinal cord injury biomarker", "inflammation biomarker", "microRNAs biomarker", "trauma biomarker", and "critically ill patients". For this study to be carried out 556 original type articles were analyzed, as well as case reports and reviews. For this review, 89 articles with relevant topics for the present paper were selected. The critically ill polytrauma patient, because of the clinical complexity the case presents with, needs a series of evaluations and specific monitoring. Recent studies show a series of either tissue-specific or circulating biomarkers that are useful in the clinical status evaluation of these patients. The biomarkers existing today, with regard to the critically ill polytrauma patient, can bring a significant contribution to increasing the survival rate, by adapting the therapy according to their expressions. Nevertheless, the necessity remains to

Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

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Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

2017-06-01

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

Biomarkers in inflammatory bowel diseases

DEFF Research Database (Denmark)

Bennike, Tue; Birkelund, Svend; Stensballe, Allan

2014-01-01

Unambiguous diagnosis of the two main forms of inflammatory bowel diseases (IBD): Ulcerative colitis (UC) and Crohn's disease (CD), represents a challenge in the early stages of the diseases. The diagnosis may be established several years after the debut of symptoms. Hence, protein biomarkers...... for early and accurate diagnostic could help clinicians improve treatment of the individual patients. Moreover, the biomarkers could aid physicians to predict disease courses and in this way, identify patients in need of intensive treatment. Patients with low risk of disease flares may avoid treatment...... with medications with the concomitant risk of adverse events. In addition, identification of disease and course specific biomarker profiles can be used to identify biological pathways involved in the disease development and treatment. Knowledge of disease mechanisms in general can lead to improved future...

Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers.

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Novakova, Lenka; Axelsson, Markus; Malmeström, Clas; Imberg, Henrik; Elias, Olle; Zetterberg, Henrik; Nerman, Olle; Lycke, Jan

2018-01-01

Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with

Biomarkers of acute lung injury: worth their salt?

Directory of Open Access Journals (Sweden)

Proudfoot Alastair G

2011-12-01

Full Text Available Abstract The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy.

Clinical value of renal injury biomarkers in diagnosis of chronic kidney disease

Directory of Open Access Journals (Sweden)

Cheng-lu ZHANG

2011-12-01

Full Text Available Objective To investigate the levels of renal injury biomarkers in patients with chronic kidney disease(CKD and evaluate their clinical significances in diagnosis of CKD.Methods A total of 66 subjects(37 patients with CKD and 29 healthy individuals were involved in this study.Serum blood urea nitrogen(SBUN was determined by Glutamate dehydrogenase method;serum creatinine(SCr and urinary creatinine(UCr were detected by sarcosine oxidase method;serum uric acid(SUA was measured by uricase colorimetry;serum cystatin C(Cys C and urinary microalbumin(UmAlbwere analyzed by immunological transmission turbidimetry;urinary protein(U-PROwas measured by Coomassies Brilliant Blue(CBB assay.The UmAlb and U-PRO levels were expressed in units of mg/mmolUCr.Results The results of independent samples t test indicated that significant differences were found in SBUN,SCr,SUA,Cys C,UmAlb and U-PRO(P < 0.05 between patient group and healthy control group.The evaluation of diagnostic effects showed that the areas under the curve at ROC plot for SBUN,SCr,SUA,Cys C,UmAlb and U-PRO were 0.907,0.912,0.742,0.982,0.984 and 0.991,respectively.Conclusions U-PRO,UmAlb and Cys C are ideal biomarkers,SCr and SBUN come next,SUA is the weakest when the above biomarkers are applied to evaluate the renal injury and its severity of the patients with CKD.

Influence of Mining Pollution on Metal Bioaccumulation and Biomarker Responses in Cave Dwelling Fish, Clarias gariepinus.

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du Preez, Gerhard; Wepener, Victor

2016-07-01

Cave ecosystems remain largely unstudied and risk being severely degraded as a result of anthropogenic activities. The Wonderfontein Cave, situated in the extensive gold mining region of the Witwatersrand Basin, is one such system that hosts a population of Clarias gariepinus, which is exposed to the influx of polluted mine water from the Wonderfontein Spruit River. The aim of this study was to investigate the bioaccumulation of metals, as well as relevant biomarkers, in C. gariepinus specimens sampled from the Wonderfontein Cave during high (April 2013) and low (September 2013) flow surveys. Results were also compared to a surface population associated with the Wonderfontein Spruit River. There were temporal differences in metal bioaccumulation patterns and this was attributed to the lack of dilution during the low flow period. Metals associated with acid mine drainage, i.e. Co, Mn and Zn were significantly higher in the Wonderfontein Cave population and were reflected in an increase in oxidative stress biomarkers (catalase, protein carbonyls and superoxide dismutase) and the induction of metallothionein, a biomarker of metal exposure. The surface population was exposed to metals associated with geological weathering processes, i.e. Fe and Al.

Biomarkers in Diabetic Retinopathy.

Science.gov (United States)

Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Biomarkers of carcinogen exposure and early effects.

OpenAIRE

2006-01-01

The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

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Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

2017-10-11

Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

Shotgun Proteomics and Biomarker Discovery

Directory of Open Access Journals (Sweden)

W. Hayes McDonald

2002-01-01

Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

Use of biomarkers in ALS drug development and clinical trials.

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Bakkar, Nadine; Boehringer, Ashley; Bowser, Robert

2015-05-14

The past decade has seen a dramatic increase in the discovery of candidate biomarkers for ALS. These biomarkers typically can either differentiate ALS from control subjects or predict disease course (slow versus fast progression). At the same time, late-stage clinical trials for ALS have failed to generate improved drug treatments for ALS patients. Incorporation of biomarkers into the ALS drug development pipeline and the use of biologic and/or imaging biomarkers in early- and late-stage ALS clinical trials have been absent and only recently pursued in early-phase clinical trials. Further clinical research studies are needed to validate biomarkers for disease progression and develop biomarkers that can help determine that a drug has reached its target within the central nervous system. In this review we summarize recent progress in biomarkers across ALS model systems and patient population, and highlight continued research directions for biomarkers that stratify the patient population to enrich for patients that may best respond to a drug candidate, monitor disease progression and track drug responses in clinical trials. It is crucial that we further develop and validate ALS biomarkers and incorporate these biomarkers into the ALS drug development process. This article is part of a Special Issue entitled ALS complex pathogenesis. Copyright © 2014 Elsevier B.V. All rights reserved.

Biomarkers of Canadian High Arctic Litoral Sediments for Assessment of Organic Matter Sources and Degradation

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Pautler, B. G.; Austin, J.; Otto, A.; Stewart, K.; Lamoureux, S. F.; Simpson, M. J.

2009-05-01

Carbon stocks in the High Arctic are particularly sensitive to global climate change, and investigation of variations in organic matter (OM) composition is beneficial for the understanding of the alteration of organic carbon under anticipated future elevated temperatures. Molecular-level characterization of solvent extractable compounds and CuO oxidation products of litoral sedimentary OM at the Cape Bounty Arctic Watershed Observatory in the Canadian Arctic Archipelago was conducted to determine the OM sources and decomposition patterns. The solvent extracts contained a series of aliphatic lipids, steroids and one triterpenoid primarily of higher plant origin and new biomarkers, iso- and anteiso-alkanes originating from cerastium arcticum (Arctic mouse-ear chickweed, a native angiosperm) were discovered. Carbon preference index (CPI) values for the n-alkanes, n-alkanols and n-alkanoic acids suggests that the OM biomarkers result from fresh material input in early stage of degradation. The CuO oxidation products were comprised of benzyls, lignin phenols and short-chain diacids and hydroxyacids. High abundance of terrestrial OM biomarkers observed at sites close to the river inlet suggests fluvial inputs as an important pathway to deliver OM into the lake. The lignin phenol vegetation index (LPVI) also suggests that the OM origin is mostly from non-woody angiosperms. A relatively high degree of lignin alteration in the litoral sediments is evident from the abundant ratio of acids and aldehydes of the vanillyl and syringyl monomers. This suggests that the lignin contents have been diagenetically altered as the result of a long residence time in this ecosystem. The molecular-level characterization of litoral sedimentary OM in Canadian High Arctic region provides insight into current OM composition,potential responses to future disturbances and the biogeochemical cycling of carbon in the Arctic.

Leukemia Associated Antigens: Their Dual Role as Biomarkers and Immunotherapeutic Targets for Acute Myeloid Leukemia

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Michael Schmitt

2007-01-01

Full Text Available Leukemia associated antigens (LAAs are being increasingly identified by methods such as cytotoxic T-lymphocyte (CTL cloning, serological analysis of recombinant cDNA expression libraries (SEREX and mass spectrometry (MS. In additional, large scale screening techniques such as microarray, single nucleotide polymorphisms (SNPs, serial analysis of gene expression (SAGE and 2-dimensional gel electrophoresis (2-DE have expanded our understanding of the role that tumor antigens play in the biological processes which are perturbed in acute myeloid leukemia (AML. It has become increasingly apparent that these antigens play a dual role, not only as targets for immunotherapy, but also as biomarkers of disease state, stage, response to treatment and survival. We need biomarkers to enable the identification of the patients who are most likely to benefit from specific treatments (conventional and/or novel and to help clinicians and scientists improve clinical end points and treatment design. Here we describe the LAAs identified in AML, to date, which have already been shown to play a dual role as biomarkers of AML disease.Abbreviations: AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; ATRA: all-trans-retinoic acid; B-CLL: B-cell chronic lymphocytic leukemia; CT: cancer-testis; CTL: cytotoxic T-lymphocyte; FAB: French-American-British; HI: hypusination inhibitors; HSP: heat shock protein; ITD: internal tandem duplication; LAA: leukemia associated antigen; MDS: myelodysplastic syndrome; MGEA6: meningioma antigen 6; MPD: myeloproliferative disease; MS: mass spectrometry; NK: natural killer; PRAME: preferentially expressed antigen of melanoma; PRTN3: proteinase 3; RAGE-1: renal antigen 1; RHAMM: receptor for hyaluronic acid-mediated motility; RQ-PCR: real-time PCR; SAGE: serial analysis of gene expression; SCT: stem cell transplant; SEREX: serological analysis of recombinant cDNA expression libraries; SNPs: single nucleotide polymorphisms; UPD

[Biomarkers of radiation-induced DNA repair processes].

Science.gov (United States)

Vallard, Alexis; Rancoule, Chloé; Guy, Jean-Baptiste; Espenel, Sophie; Sauvaigo, Sylvie; Rodriguez-Lafrasse, Claire; Magné, Nicolas

2017-11-01

The identification of DNA repair biomarkers is of paramount importance. Indeed, it is the first step in the process of modulating radiosensitivity and radioresistance. Unlike tools of detection and measurement of DNA damage, DNA repair biomarkers highlight the variations of DNA damage responses, depending on the dose and the dose rate. The aim of the present review is to describe the main biomarkers of radiation-induced DNA repair. We will focus on double strand breaks (DSB), because of their major role in radiation-induced cell death. The most important DNA repair biomarkers are DNA damage signaling proteins, with ATM, DNA-PKcs, 53BP1 and γ-H2AX. They can be analyzed either using immunostaining, or using lived cell imaging. However, to date, these techniques are still time and money consuming. The development of "omics" technologies should lead the way to new (and usable in daily routine) DNA repair biomarkers. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Resistance to valproic acid as predictor of treatment resistance in genetic generalized epilepsies

DEFF Research Database (Denmark)

Gesche, Joanna; Khanevski, Marina; Solberg, Carl

2017-01-01

for refractory seizures. Resistance to valproic acid had a specificity of 100% to identify patients with drug resistance and correlated strongly with bad social outcome and seizure burden. Conversely, 21.2% of all patients with refractory seizures according to the ILAE definition later became seizure free...... (mainly with valproic acid). Our data suggest that "drug resistant GGE" must not be declared unless patients were adequately treated with valproic acid, and advocate resistance to valproic acid as a new clinical biomarker for drug-resistant GGE. A PowerPoint slide summarizing this article is available...

The Biomarker Knowledge System Informatics Pilot Project Supplement To The Biomarker Development Laboratory at Moffitt (Bedlam) — EDRN Public Portal

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The Biomarker Knowledge System Informatics Pilot Project goal will develop network interfaces among databases that contain information about existing clinical populations and biospecimens and data relating to those specimens that are important in biomarker assay validation. This protocol comprises one of two that will comprise the Moffitt participation in the Biomarker Knowledge System Informatics Pilot Project. THIS PROTOCOL (58) is the Sput-Epi Database.

The effects of Bifidobacteria on the lipid profile and oxidative stress biomarkers of male rats fed thermally oxidized soybean oil.

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Awney, Hala A

2011-08-01

Over the years, there has been concern about the changes taking place in heated oils and the effects on individuals consuming them. The present study investigated the effects of a diet containing thermally oxidized soybean oil (TO) or TO supplemented with probiotic Bifidobacteria (TO+Pro) on the serum lipid profile and oxidative stress biomarkers of male rats. The data showed several indicators of oil deterioration after thermal processing, including high levels of % free fatty acid (FFA; 15-fold), acid value (AV; 14-fold), peroxide value (8-fold), p-anisidine value (AnV; 39-fold), total oxidation value (TOTOX; 19-fold), thiobarbituric acid-reactive substances (TBARS) value (8.5-fold), and trans-FA (TFA) isomers (2.5-fold) compared to the control. The rats that were fed a diet containing TO showed a significant (p blood serum samples. High levels of TBARS, superoxide dismutase (SOD), and glutathione reductase (GR) activities were also detected in the livers, kidneys, testes, and brains of rats. Interestingly, a diet containing TO+Pro restored all biological parameters to their control values. The present data suggested that Bifidobacteria may ameliorate the serum lipid profile and oxidative stress biomarkers that are generated in animals that are fed a TO diet.

Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

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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.

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

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Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-01-01

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

Biomarkers of exposure and dose: State of the art

International Nuclear Information System (INIS)

Brooks, A.L.

2001-01-01

Biomarkers provide methods to measure changes in biological systems and to relate them to environmental insults and disease processes. Biomarkers can be classified as markers of exposure and dose, markers of sensitivity, and markers of disease. It is important that the differences and applications of the various types of biomarkers be clearly understood. The military is primarily interested in early biomarkers of exposure and dose that do not require high levels of sensitivity but can be used to rapidly triage war fighters under combat or terrorist conditions and determine which, if any, require medical attention. Biomarkers of long-term radiation risk represent the second area of interest for the military. Biomarkers of risk require high sensitivity and specificity for the disease and insult but do not require rapid data turn around. Biomarkers will help provide information for quick command decisions in the field, characterise long-term troop risks and identify early stages of radiation-induced diseases. This information provides major positive reassurances about individual exposures and risk that will minimise the physical and psychological impact of wartime radiation exposures. (author)

Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

Science.gov (United States)

Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

2016-02-07

Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

The New Digital Divide For Digital BioMarkers.

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Torous, John; Rodriguez, Jorge; Powell, Adam

2017-09-01

As smartphone and sensors continue to become more ubiquitous across the world, digital biomarkers have emerged as a scalable and practical tool to explore disease states and advance health. But as the digital divide of access and ownership begins to fade, a new digital divide is emerging. Who are the types of people that own smartphones or smart watches, who are the types of people that download health apps or partake in digital biomarker studies, and who are the types of people that are actually active with digital biomarkers apps and sensors - the people providing the high quality and longitudinal data that this field is being founded upon? Understanding the people behind digital biomarkers, the very people this emerging field aims to help, may actually be the real challenge as well as opportunity for digital biomarkers.

Phase II cancer clinical trials for biomarker-guided treatments.

Science.gov (United States)

Jung, Sin-Ho

2018-01-01

The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

Systems biology and biomarker discovery

Energy Technology Data Exchange (ETDEWEB)

Rodland, Karin D.

2010-12-01

Medical practitioners have always relied on surrogate markers of inaccessible biological processes to make their diagnosis, whether it was the pallor of shock, the flush of inflammation, or the jaundice of liver failure. Obviously, the current implementation of biomarkers for disease is far more sophisticated, relying on highly reproducible, quantitative measurements of molecules that are often mechanistically associated with the disease in question, as in glycated hemoglobin for the diagnosis of diabetes [1] or the presence of cardiac troponins in the blood for confirmation of myocardial infarcts [2]. In cancer, where the initial symptoms are often subtle and the consequences of delayed diagnosis often drastic for disease management, the impetus to discover readily accessible, reliable, and accurate biomarkers for early detection is compelling. Yet despite years of intense activity, the stable of clinically validated, cost-effective biomarkers for early detection of cancer is pathetically small and still dominated by a handful of markers (CA-125, CEA, PSA) first discovered decades ago. It is time, one could argue, for a fresh approach to the discovery and validation of disease biomarkers, one that takes full advantage of the revolution in genomic technologies and in the development of computational tools for the analysis of large complex datasets. This issue of Disease Markers is dedicated to one such new approach, loosely termed the 'Systems Biology of Biomarkers'. What sets the Systems Biology approach apart from other, more traditional approaches, is both the types of data used, and the tools used for data analysis - and both reflect the revolution in high throughput analytical methods and high throughput computing that has characterized the start of the twenty first century.

A New Serum Biomarker for Lung Cancer - Transthyretin

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Liyun LIU

2009-04-01

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

Biomarkers of replicative senescence revisited

DEFF Research Database (Denmark)

Nehlin, Jan

2016-01-01

Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

The Janus serum bank and biomarkers of cancer

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Randi Gislefoss

2009-10-01

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

Omega-3 polyunsaturated fatty acid blood biomarkers increase linearly in men and women after tightly controlled intakes of 0.25, 0.5, and 1 g/d of EPA + DHA.

Science.gov (United States)

Patterson, Ashley C; Chalil, Alan; Aristizabal Henao, Juan J; Streit, Isaac T; Stark, Ken D

2015-12-01

Blood levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been related to coronary heart disease risk. Understanding the response of EPA + DHA in blood to dietary intake of EPA + DHA would facilitate the use of blood measures as markers of adherence and enable the development of dietary recommendations. The objective of this study is examine the blood response to intakes of EPA + DHA ≤1 g/d with an intervention designed for dietary adherence. It was hypothesized this relationship would be linear and that intakes of EPA + DHA DHA intake of men and women (n = 20) was determined by food frequency questionnaire and adherence was monitored by weekly fingertip blood sampling for fatty acid determinations. Participants consumed nutraceuticals to achieve intakes of 0.25 g/d and 0.5 g/d EPA + DHA for successive four-week periods. A subgroup (n = 5) had intakes of 1.0 g/d EPA + DHA for an additional 4 weeks. Fatty acid composition of whole blood, erythrocytes, and plasma phospholipids were determined at each time point. Blood levels of EPA and DHA increased linearly in these pools. A comprehensive review of the literature was used to verify the blood-intake relationship. Blood levels of long chain omega-3 polyunsaturated fatty acids reached blood levels associated with the highest levels of primary cardiac arrest reduction and sudden cardiac death risk only with intakes of 1.0 g/d of EPA + DHA. The blood biomarker response to intakes of EPA + DHA ≤1 g/d is linear in a small but highly adherent study sample and this information can assist in determining adherence in clinical studies and help identify dietary intake targets from associations between blood and disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Low serum hyaluronic acid levels associated with spontaneous HBsAg clearance

NARCIS (Netherlands)

Harkisoen, S.; Arends, J. E.; van den Hoek, A.; van Erpecum, K. J.; Boland, G. J.; Hoepelman, A. I. M.

2015-01-01

Purpose The pathophysiological underlying mechanism of spontaneous HBsAg clearance in hepatitis B virus (HBV) infected patients is largely unknown. However, serum hyaluronic acid (sHA) plays a role in liver fibrosis progression and reversely could serve as a potential biomarker for HBsAg clearance.

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

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Yasser E Nassef

2013-11-01

Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

amphibian_biomarker_data

Data.gov (United States)

U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

Challenging homeostasis to define biomarkers for nutrition related health

NARCIS (Netherlands)

Ommen, van B.; Keijer, J.; Heil, S.G.; Kaput, J.

2009-01-01

A primary goal of nutrition research is to optimize health and prevent or delay disease. Biomarkers to quantify health optimization are needed since many if not most biomarkers are developed for diseases. Quantifying normal homeostasis and developing validated biomarkers are formidable tasks because

Serum Amino Acid Profiles in Normal Subjects and in Patients with or at Risk of Alzheimer Dementia.

Science.gov (United States)

Corso, Gaetano; Cristofano, Adriana; Sapere, Nadia; la Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Fratangelo, Roberto; Lombardi, Teresa; Porcile, Carola; Intrieri, Mariano; Di Costanzo, Alfonso

2017-01-01

Abnormalities in the plasma amino acid profile have been reported in Alzheimer disease (AD), but no data exist for the prodromal phase characterized by subjective memory complaint (SMC). It was our aim to understand if serum amino acid levels change along the continuum from normal to AD, and to identify possible diagnostic biomarkers. Serum levels of 15 amino acids and 2 organic acids were determined in 4 groups of participants - 29 with probable AD, 18 with mild cognitive impairment (MCI), 24 with SMC, and 46 cognitively healthy subjects (HS) - by electrospray tandem mass spectrometry. Glutamate, aspartate, and phenylalanine progressively decreased, while citrulline, argi-ninosuccinate, and homocitrulline progressively increased, from HS over SMC and MCI to AD. The panel including these 6 amino acids and 4 ratios (glutamate/citrulline, citrulline/phenylalanine, leucine plus isoleucine/phenylalanine, and arginine/phenylalanine) discriminated AD from HS with about 96% accuracy. Other panels including 20 biomarkers discriminated SMC or MCI from AD or HS with an accuracy ranging from 88 to 75%. Amino acids contribute to a characteristic metabotype during the progression of AD along the continuum from health to frank dementia, and their monitoring in elderly individuals might help to detect at-risk subjects.

Association of oxidative stress biomarkers with adiposity and clinical staging in women with breast cancer.

Science.gov (United States)

Carioca, A A F; Verde, S M M L; Luzia, L A; Rondó, P H C; Latorre, M R D O; Ellery, T H P; Damasceno, N R T

2015-11-01

Breast cancer is a disease characterised by both oxidative reactions and inflammation. However, few studies have focused on the oxidative and inflammatory biomarkers. The aim of the present study was to evaluate the association between oxidative stress markers and adiposity and clinical staging, as well as the association between the oxidative and the antioxidant biomarkers of women with breast cancer. A total of 135 cases of breast cancer occurring in 2011 and 2012 were assessed. After exclusions, 101 pre- and post-menopausal women with clinical staging I to IV were eligible to participate in the study. The anthropometric evaluation was performed by collecting data on waist circumference, body mass index and body composition. The socioeconomic and clinical profiles were determined using a standard questionnaire. For the oxidative biomarkers, thiobarbituric acid reactive substances (TBARS), oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), low-density lipoprotein(-) (LDL(-)), autoantibody anti-LDL(-) and liposoluble antioxidants (α-tocopherol, retinol and β-carotene) were analysed. The data were analysed using differences in the mean values, correlation tests and multiple linear regression. The antioxidant levels were higher in postmenopausal women with clinical staging I and II and negative lymph nodes. The TBARS level was associated with clinical staging. Adiposity was associated with levels of retinol and 8-OHdG, whereas LDL(-), 8-OHdG and TBARS were correlated with liposoluble antioxidants after adjusting for the confounders. The adiposity and clinical staging of patients were associated with oxidative stress. The oxidative and antioxidant biomarkers showed a negative correlation in patients with breast cancer.

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet’s Disease by Gas Chromatography/Time-of-Flight−Mass Spectrometry

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Joong Kyong Ahn

2017-11-01

Full Text Available Diagnosing Behcet’s disease (BD is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS. Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA model were R2X of 0.231, R2Y of 0.804, and Q2 of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974. OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%. We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.

Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

Science.gov (United States)

Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

2018-06-01

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

A tuberculosis biomarker database: the key to novel TB diagnostics

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Seda Yerlikaya

2017-03-01

Full Text Available New diagnostic innovations for tuberculosis (TB, including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this ‘biomarker pipeline problem’, FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools.

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children

Directory of Open Access Journals (Sweden)

Nicolai A. Lund-Blix

2016-08-01

Full Text Available Background: There is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children. Objective: The objective was to evaluate the suitability of a food frequency questionnaire (FFQ to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA, and docosahexaenoic acid (DHA. Design: Cross-sectional data for the present study were derived from the prospective cohort ‘Environmental Triggers of Type 1 Diabetes Study’. Infants were recruited from the Norwegian general population during 2001–2007. One hundred and ten (age 3–10 years children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution. Results: Significant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29, total fat dairy products (r=0.39, and cheese products (r=0.36. EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA. To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker. Conclusions: The present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children.

Science.gov (United States)

Lund-Blix, Nicolai A; Rønningen, Kjersti S; Bøås, Håkon; Tapia, German; Andersen, Lene F

2016-01-01

There is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children. The objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Cross-sectional data for the present study were derived from the prospective cohort 'Environmental Triggers of Type 1 Diabetes Study'. Infants were recruited from the Norwegian general population during 2001-2007. One hundred and ten (age 3-10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution. Significant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker. The present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content and cod liver/fish oil supplements.

Use of ribosomal proteins as biomarkers for identification of Flavobacterium psychrophilum by MALDI-TOF mass spectrometry.

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Fernández-Álvarez, Clara; Torres-Corral, Yolanda; Santos, Ysabel

2018-01-06

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) is a rapid methodology for identification of bacteria that is increasingly used in diagnostic laboratories. This work aimed at evaluating the potential of MALDI-TOF-MS for identification of the main serotypes of Flavobacterium psychrophilum isolated from salmonids, and its discrimination from closely related Flavobacterium spp. A mass spectra library was constructed by analysing 70 F. psychrophilum strains representing the serotypes O1, O2a, O2b and O3, including reference and clinical isolates. Peak mass lists were examined using the Mass-Up software for the detection of potential biomarkers, similarity and cluster analysis. Fourteen species-identifying biomarkers were detected in all the F. psychrophilum isolates tested, moreover, sets of serotype-identifying biomarkers ions were selected. F. psychrophilum-specific biomarkers were identified as ribosomal proteins by matching with protein databases. Furthermore, sequence variation corresponding to amino acid exchanges in several biomarker proteins were tentatively assigned. Closely related Flavobacterium species (F. flevense, F. succinicans, F. columnare, F. branchiophilum and F. johnsoniae) could be differentiated from F. psychrophilum by defining species identifying biomarkers and hierarchical cluster analysis. These results demonstrated that MALDI-TOF spectrometry represents a powerful tool for an accurate identification of the fish pathogen F. psychrophilum as well as for epidemiological studies. The results obtained in this study demonstrated that MALDI-TOF mass spectrometry represents a powerful tool that can be used by diagnostic laboratories for rapid identification of the fish pathogen Flavobacterium psychrophilum and its differentiation from other Flavobacterium-related species. Analysis of mass peak lists revealed the potential of the MALDI-TOF technique to identify epidemiologically important serotypes affecting

A Taiwanese food frequency questionnaire correlates with plasma docosahexaenoic acid but not with plasma eicosapentaenoic acid levels: questionnaires and plasma biomarkers.

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Chien, Kuo-Liong; Lee, Meei-Shyuan; Tsai, Yi-Tsen; Chen, Pey-Rong; Lin, Hung-Ju; Hsu, Hsiu-Ching; Lee, Yuan-The; Chen, Ming-Fong

2013-02-16

Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration. We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (± SD) age of 59.8 (±12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography. The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions

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Radu M. Nanau

2015-06-01

Full Text Available Background: The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. Methods: A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010–2015. The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Findings: Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

Biomolecules and Biomarkers Used in Diagnosis of Alcohol Drinking and in Monitoring Therapeutic Interventions.

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Nanau, Radu M; Neuman, Manuela G

2015-06-29

The quantitative, measurable detection of drinking is important for the successful treatment of alcohol misuse in transplantation of patients with alcohol disorders, people living with human immunodeficiency virus that need to adhere to medication, and special occupational hazard offenders, many of whom continually deny drinking. Their initial misconduct usually leads to medical problems associated with drinking, impulsive social behavior, and drunk driving. The accurate identification of alcohol consumption via biochemical tests contributes significantly to the monitoring of drinking behavior. A systematic review of the current methods used to measure biomarkers of alcohol consumption was conducted using PubMed and Google Scholar databases (2010-2015). The names of the tests have been identified. The methods and publications that correlate between the social instruments and the biochemical tests were further investigated. There is a clear need for assays standardization to ensure the use of these biochemical tests as routine biomarkers. Alcohol ingestion can be measured using a breath test. Because alcohol is rapidly eliminated from the circulation, the time for detection by this analysis is in the range of hours. Alcohol consumption can alternatively be detected by direct measurement of ethanol concentration in blood or urine. Several markers have been proposed to extend the interval and sensitivities of detection, including ethyl glucuronide and ethyl sulfate in urine, phosphatidylethanol in blood, and ethyl glucuronide and fatty acid ethyl esters in hair, among others. Moreover, there is a need to correlate the indirect biomarker carbohydrate deficient transferrin, which reflects longer lasting consumption of higher amounts of alcohol, with serum γ-glutamyl transpeptidase, another long term indirect biomarker that is routinely used and standardized in laboratory medicine.

Crevicular fluid biomarkers and periodontal disease progression.

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Kinney, Janet S; Morelli, Thiago; Oh, Min; Braun, Thomas M; Ramseier, Christoph A; Sugai, Jim V; Giannobile, William V

2014-02-01

Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biomarkers: in medicine, drug discovery, and environmental health

National Research Council Canada - National Science Library

Vaidya, Vishal S; Bonventre, Joseph V

2010-01-01

... Identification Using Mass Spectrometry Sample Preparation Protein Quantitation Examples of Biomarker Discovery and Evaluation Challenges in Proteomic Biomarker Discovery The Road Forward: Targeted ...

What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema.

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Ptolemy, Adam S; Rifai, Nader

2010-01-01

A continual trend of annual growth can be seen within research devoted to the discovery and validation of disease biomarkers within both the natural and clinical sciences. This expansion of intellectual endeavours was quantified through database searches of (a) research grant awards provided by the various branches of the National Institutes of Health (NIH) and (b) academic publications. A search of awards presented between 1986 and 2009 revealed a total of 28,856 grants awarded by the NIH containing the term "biomarker". The total funds for these awards in 2008 and 2009 alone were over $2.5 billion. During the same respective time frames, searches of "biomarker" and either "discovery", "genomics", "proteomics" or "metabolomics" yielded a total of 4,928 NIH grants whose combined funding exceeded $1.2 billion. The derived trend in NIH awards paralleled the annual expansion in "biomarker" literature. A PubMed search for the term, between 1990 and 2009, revealed a total of 441,510 published articles, with 38,457 published in 2008. These enormous investments and academic outputs however have not translated into the expected integration of new biomarkers for patient care. For example no proteomics derived biomarkers are currently being utilized in routine clinical management. This translational chasm necessitates a review of the previously proposed biomarker definitions and evaluation schema. A subsequent discussion of both the analytical and pre-analytical considerations for such research is also presented within. This required knowledge should aid scientists in their pursuit and validation of new biological markers of disease.

Sedimentary organic biomarkers suggest detrimental effects of PAHs on estuarine microbial biomass during the 20th century in San Francisco Bay, CA, USA

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Nilsen, Elena B.; Rosenbauer, Robert J.; Fuller, Christopher C.; Jaffe, Bruce E.

2014-01-01

Hydrocarbon contaminants are ubiquitous in urban aquatic ecosystems, and the ability of some microbial strains to degrade certain polycyclic aromatic hydrocarbons (PAHs) is well established. However, detrimental effects of petroleum hydrocarbon contamination on nondegrader microbial populations and photosynthetic organisms have not often been considered. In the current study, fatty acid methyl ester (FAME) biomarkers in the sediment record were used to assess historical impacts of petroleum contamination on microbial and/or algal biomass in South San Francisco Bay, CA, USA. Profiles of saturated, branched, and monounsaturated fatty acids had similar concentrations and patterns downcore. Total PAHs in a sediment core were on average greater than 20× higher above ∼200 cm than below, which corresponds roughly to the year 1900. Isomer ratios were consistent with a predominant petroleum combustion source for PAHs. Several individual PAHs exceeded sediment quality screening values. Negative correlations between petroleum contaminants and microbial and algal biomarkers – along with high trans/cis ratios of unsaturated FA, and principle component analysis of the PAH and fatty acid records – suggest a negative impacts of petroleum contamination, appearing early in the 20th century, on microbial and/or algal ecology at the site.

Blood cells transcriptomics as source of potential biomarkers of articular health improvement: effects of oral intake of a rooster combs extract rich in hyaluronic acid.

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Sánchez, Juana; Bonet, M Luisa; Keijer, Jaap; van Schothorst, Evert M; Mölller, Ingrid; Chetrit, Carles; Martinez-Puig, Daniel; Palou, Andreu

2014-09-01

The aim of the study was to explore peripheral blood gene expression as a source of biomarkers of joint health improvement related to glycosaminoglycan (GAG) intake in humans. Healthy individuals with joint discomfort were enrolled in a randomized, double-blind, placebo-controlled intervention study in humans. Subjects ate control yoghurt or yoghurt supplemented with a recently authorized novel food in Europe containing hyaluronic acid (65 %) from rooster comb (Mobilee™ as commercial name) for 90 days. Effects on functional quality-of-life parameters related to joint health were assessed. Whole-genome microarray analysis of peripheral blood samples from a subset of 20 subjects (10 placebo and 10 supplemented) collected pre- and post-intervention was performed. Mobilee™ supplementation reduced articular pain intensity and synovial effusion and improved knee muscular strength indicators as compared to placebo. About 157 coding genes were differentially expressed in blood cells between supplemented and placebo groups post-intervention, but not pre-intervention (p < 0.05; fold change ≥1.2). Among them, a reduced gene expression of glucuronidase-beta (GUSB), matrix metallopeptidase 23B (MMP23B), xylosyltransferase II (XYLT2), and heparan sulfate 6-O-sulfotransferase 1 (HS6ST1) was found in the supplemented group. Correlation analysis indicated a direct relationship between blood cell gene expression of MMP23B, involved in the breakdown of the extracellular matrix, and pain intensity, and an inverse relationship between blood cell gene expression of HS6ST1, responsible for 6-O-sulfation of heparan sulfate, and indicators of knee muscular strength. Expression levels of specific genes in blood cells, in particular genes related to GAG metabolism and extracellular matrix dynamics, are potential biomarkers of beneficial effects on articular health.

Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats

Energy Technology Data Exchange (ETDEWEB)

Yamazaki, Makoto; Miyake, Manami; Sato, Hiroko; Masutomi, Naoya; Tsutsui, Naohisa [Mitsubishi Tanabe Pharma Corporation, Kisarazu, Chiba 292-0818 (Japan); Adam, Klaus-Peter; Alexander, Danny C.; Lawton, Kay A.; Milburn, Michael V.; Ryals, John A.; Wulff, Jacob E. [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States); Guo, Lining, E-mail: lguo@metabolon.com [Metabolon Inc., 617 Davis Drive, Suite 400, Durham, NC 27713 (United States)

2013-04-01

Drug-induced liver injury (DILI) is a significant consideration for drug development. Current preclinical DILI assessment relying on histopathology and clinical chemistry has limitations in sensitivity and discordance with human. To gain insights on DILI pathogenesis and identify potential biomarkers for improved DILI detection, we performed untargeted metabolomic analyses on rats treated with thirteen known hepatotoxins causing various types of DILI: necrosis (acetaminophen, bendazac, cyclosporine A, carbon tetrachloride, ethionine), cholestasis (methapyrilene and naphthylisothiocyanate), steatosis (tetracycline and ticlopidine), and idiosyncratic (carbamazepine, chlorzoxasone, flutamide, and nimesulide) at two doses and two time points. Statistical analysis and pathway mapping of the nearly 1900 metabolites profiled in the plasma, urine, and liver revealed diverse time and dose dependent metabolic cascades leading to DILI by the hepatotoxins. The most consistent change induced by the hepatotoxins, detectable even at the early time point/low dose, was the significant elevations of a panel of bile acids in the plasma and urine, suggesting that DILI impaired hepatic bile acid uptake from the circulation. Furthermore, bile acid amidation in the hepatocytes was altered depending on the severity of the hepatotoxin-induced oxidative stress. The alteration of the bile acids was most evident by the necrosis and cholestasis hepatotoxins, with more subtle effects by the steatosis and idiosyncratic hepatotoxins. Taking together, our data suggest that the perturbation of bile acid homeostasis is an early event of DILI. Upon further validation, selected bile acids in the circulation could be potentially used as sensitive and early DILI preclinical biomarkers. - Highlights: ► We used metabolomics to gain insights on drug induced liver injury (DILI) in rats. ► We profiled rats treated with thirteen hepatotoxins at two doses and two time points. ► The toxins decreased the

Circulating biomarkers for predicting cardiovascular disease risk; a systematic review and comprehensive overview of meta-analyses.

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Thijs C van Holten

Full Text Available BACKGROUND: Cardiovascular disease is one of the major causes of death worldwide. Assessing the risk for cardiovascular disease is an important aspect in clinical decision making and setting a therapeutic strategy, and the use of serological biomarkers may improve this. Despite an overwhelming number of studies and meta-analyses on biomarkers and cardiovascular disease, there are no comprehensive studies comparing the relevance of each biomarker. We performed a systematic review of meta-analyses on levels of serological biomarkers for atherothrombosis to compare the relevance of the most commonly studied biomarkers. METHODS AND FINDINGS: Medline and Embase were screened on search terms that were related to "arterial ischemic events" and "meta-analyses". The meta-analyses were sorted by patient groups without pre-existing cardiovascular disease, with cardiovascular disease and heterogeneous groups concerning general populations, groups with and without cardiovascular disease, or miscellaneous. These were subsequently sorted by end-point for cardiovascular disease or stroke and summarized in tables. We have identified 85 relevant full text articles, with 214 meta-analyses. Markers for primary cardiovascular events include, from high to low result: C-reactive protein, fibrinogen, cholesterol, apolipoprotein B, the apolipoprotein A/apolipoprotein B ratio, high density lipoprotein, and vitamin D. Markers for secondary cardiovascular events include, from high to low result: cardiac troponins I and T, C-reactive protein, serum creatinine, and cystatin C. For primary stroke, fibrinogen and serum uric acid are strong risk markers. Limitations reside in that there is no acknowledged search strategy for prognostic studies or meta-analyses. CONCLUSIONS: For primary cardiovascular events, markers with strong predictive potential are mainly associated with lipids. For secondary cardiovascular events, markers are more associated with ischemia. Fibrinogen is a

Biomarkers, Trauma, and Sepsis in Pediatrics: A Review

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Marianne Frieri

2016-01-01

Full Text Available Context: There is a logical connection with biomarkers, trauma, and sepsis. This review paper provides new information and clinical practice implications. Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Stress management both in trauma is based upon the notion that stress causes an immune imbalance in susceptible individuals. Evidence Acquisition: Data sources included studies indexed in PubMed, a meta- analysis, predictive values, research strategies, and quality assessments. A recent paper by one of the authors stated marked increase in serum procalcitonin during the course of a septic process often indicates an exacerbation of the illness, and a decreasing level is a sign of improvement. A review of epidemiologic studies on pediatric soccer patients was also addressed. Keywords for searching included biomarkers, immunity, trauma, and sepsis. Results: Of 50 reviewed articles, 34 eligible articles were selected including biomarkers, predictive values for procalcitonin, identifying children at risk for intra-abdominal injuries, blunt trauma, and epidemiology, a meta-analysis. Of neonatal associated sepsis, the NF-kappa B pathway by inflammatory stimuli in human neutrophils, predictive value of gelsolin for the outcomes of preterm neonates, a meta-analysis interleukin-8 for neonatal sepsis diagnosis. Conclusions: Biomarkers are very important especially in pediatrics. Procalcitonin and other biomarkers are helpful in identifying neonatal sepsis, defense mechanisms, and physiological functions of the immune system. Pediatric trauma and sepsis is very important both in infants and in children. Various topics were covered such as biomarkers, trauma, sepsis, inflammation, innate immunity, role of neutrophils and IL-8, reactive oxygen species

Biomarkers of Nutrition for Development—Iodine Review1234

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Rohner, Fabian; Zimmermann, Michael; Jooste, Pieter; Pandav, Chandrakant; Caldwell, Kathleen; Raghavan, Ramkripa; Raiten, Daniel J.

2014-01-01

The objective of the Biomarkers of Nutrition for Development (BOND) project is to provide state-of-the-art information and service with regard to selection, use, and interpretation of biomarkers of nutrient exposure, status, function, and effect. Specifically, the BOND project seeks to develop consensus on accurate assessment methodologies that are applicable to researchers (laboratory/clinical/surveillance), clinicians, programmers, and policy makers (data consumers). The BOND project is also intended to develop targeted research agendas to support the discovery and development of biomarkers through improved understanding of nutrient biology within relevant biologic systems. In phase I of the BOND project, 6 nutrients (iodine, vitamin A, iron, zinc, folate, and vitamin B-12) were selected for their high public health importance because they typify the challenges faced by users in the selection, use, and interpretation of biomarkers. For each nutrient, an expert panel was constituted and charged with the development of a comprehensive review covering the respective nutrient’s biology, existing biomarkers, and specific issues of use with particular reference to the needs of the individual user groups. In addition to the publication of these reviews, materials from each will be extracted to support the BOND interactive Web site (http://www.nichd.nih.gov/global_nutrition/programs/bond/pages/index.aspx). This review represents the first in the series of reviews and covers all relevant aspects of iodine biology and biomarkers. The article is organized to provide the reader with a full appreciation of iodine’s background history as a public health issue, its biology, and an overview of available biomarkers and specific considerations for the use and interpretation of iodine biomarkers across a range of clinical and population-based uses. The review also includes a detailed research agenda to address priority gaps in our understanding of iodine biology and assessment

DNA Methylation Alterations Associated with Latent Carcinogenic Activity of Dichloroacetic Acid in Mice

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Early-life environmental factors can influence later-life susceptibility to cancer. Epigenetic changes serve as promising biomarkers for these latent effects. Previously, we reported that short-term postnatal exposure to dichloroacetic acid (DCA), a byproduct of drinking water ch...

Biomarkers in Diabetic Retinopathy

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Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

2015-01-01

There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

Diagnosing phenotypes of single-sample individuals by edge biomarkers.

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Zhang, Wanwei; Zeng, Tao; Liu, Xiaoping; Chen, Luonan

2015-06-01

Network or edge biomarkers are a reliable form to characterize phenotypes or diseases. However, obtaining edges or correlations between molecules for an individual requires measurement of multiple samples of that individual, which are generally unavailable in clinical practice. Thus, it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual context. Here, we developed a new computational framework, EdgeBiomarker, to integrate edge and node biomarkers to diagnose phenotype of each single test sample. By applying the method to datasets of lung and breast cancer, it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer stages. Our method shows advantages over traditional methods: (i) edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes, suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods; (ii) edge biomarkers categorize patients into low/high survival rate in a more reliable manner; (iii) edge biomarkers are significantly enriched in relevant biological functions or pathways, implying that the association changes in a network, rather than expression changes in individual molecules, tend to be causally related to cancer development. The new framework of edge biomarkers paves the way for diagnosing diseases and analyzing their molecular mechanisms by edges or networks in one-sample-for-one-individual basis. This also provides a powerful tool for precision medicine or big-data medicine. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

[Biomarkers of Alzheimer disease].

Science.gov (United States)

Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

2014-01-01

Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

Biomarkers in natural fish populations indicate adverse biological effects of offshore oil production.

Directory of Open Access Journals (Sweden)

Lennart Balk

Full Text Available Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills.Samples from natural populations of haddock (Melanogrammus aeglefinus and Atlantic cod (Gadus morhua in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea.It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production.

Metabolomics as a tool in the identification of dietary biomarkers.

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Gibbons, Helena; Brennan, Lorraine

2017-02-01

Current dietary assessment methods including FFQ, 24-h recalls and weighed food diaries are associated with many measurement errors. In an attempt to overcome some of these errors, dietary biomarkers have emerged as a complementary approach to these traditional methods. Metabolomics has developed as a key technology for the identification of new dietary biomarkers and to date, metabolomic-based approaches have led to the identification of a number of putative biomarkers. The three approaches generally employed when using metabolomics in dietary biomarker discovery are: (i) acute interventions where participants consume specific amounts of a test food, (ii) cohort studies where metabolic profiles are compared between consumers and non-consumers of a specific food and (iii) the analysis of dietary patterns and metabolic profiles to identify nutritypes and biomarkers. The present review critiques the current literature in terms of the approaches used for dietary biomarker discovery and gives a detailed overview of the currently proposed biomarkers, highlighting steps needed for their full validation. Furthermore, the present review also evaluates areas such as current databases and software tools, which are needed to advance the interpretation of results and therefore enhance the utility of dietary biomarkers in nutrition research.

Implementation of proteomic biomarkers : Making it work

NARCIS (Netherlands)

Mischak, Harald; Ioannidis, John P. A.; Argiles, Angel; Attwood, Teresa K.; Bongcam-Rudloff, Erik; Broenstrup, Mark; Charonis, Aristidis; Chrousos, George P.; Delles, Christian; Dominiczak, Anna; Dylag, Tomasz; Ehrich, Jochen; Egido, Jesus; Findeisen, Peter; Jankowski, Joachim; Johnson, Robert W.; Julien, Bruce A.; Lankisch, Tim; Leung, Hing Y.; Maahs, David; Magni, Fulvio; Manns, Michael P.; Manolis, Efthymios; Mayer, Gert; Navis, Gerarda; Novak, Jan; Ortiz, Alberto; Persson, Frederik; Peter, Karlheinz; Riese, Hans H.; Rossing, Peter; Sattar, Naveed; Spasovski, Goce; Thongboonkerd, Visith; Vanholder, Raymond; Schanstra, Joost P.; Vlahou, Antonia

Eur J Clin Invest 2012; 42 (9): 10271036 Abstract While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe

Assessment of consumption of marine food in Greenland by a food frequency questionnaire and biomarkers

Directory of Open Access Journals (Sweden)

Charlotte Jeppesen

2012-05-01

Full Text Available Objectives. We studied the association and agreement between questionnaire data and biomarkers of marine food among Greenland Inuit. Design. Cross sectional study. Methods. The study population comprised 2,224 Inuit, age 18+ (43% men; data collected 2005–2008 in Greenland. Using a food frequency questionnaire (FFQ, we calculated consumption of seal, whale, and fish (g/day and as meals/month, intake of eicosapentaenoic acid (EPA, docosahexaenoic acid (DHA, total N3, and mercury. We measured erythrocyte membrane fatty acids (FA and whole blood mercury (Hg. Associations were assessed by Pearson correlation and agreement between the 2 methods was assessed by Bland–Altman plots depicting mean difference between the methods. Using multiple linear regressions, the associations were studied between whole blood mercury, erythrocyte FA and frequency or gram per day of seal, whale, and fish. Results. Partial correlations ranged from r=0.16, p<0.0001 (DHA to r=0.56, p<0.0001 (mercury. The best fitted lines were found for mercury and DHA. Mean difference was negative for mercury but positive for all the FA biomarkers. In a multiple logistic regression analysis, the best association was found between whole blood mercury and seal consumption, both as frequency in meals and actual intake gram per day: β=1.07 µg (95% CI: 1.06; 1.08 and β=1.04 µg (95% CI: 1.03; 1.04, respectively. Conclusion. Mercury showed the best correlation and agreement between calculated and measured values. Calculated actual intake in gram per day and frequency of meals showed similar associations with whole blood mercury and erythrocyte membrane FAs.

Novel biomarkers for prediabetes, diabetes, and associated complications

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Dorcely B

2017-08-01

Full Text Available Brenda Dorcely,1 Karin Katz,1 Ram Jagannathan,2 Stephanie S Chiang,1 Babajide Oluwadare,1 Ira J Goldberg,1 Michael Bergman1 1New York University School of Medicine, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, NYU Langone Medical Center, New York, NY, 2Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA Abstract: The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c, fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recogni­zing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. Keywords: prediabetes, biomarkers, inflammatory markers, diabetes, diabetes complications

Using Aptamers for Cancer Biomarker Discovery

Directory of Open Access Journals (Sweden)

Yun Min Chang

2013-01-01

Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

Characterization of the europium tetracycline complex as a biomarker for atherosclerosis

Science.gov (United States)

Courrol, Lilia C.; da Silva, Mônica N.; Sicchieri, Leticia B.

2016-04-01

Atherosclerosis is a narrowing of the arteries caused by an increase of atheromatous plaque: material formed by macrophage cells containing cholesterol and fatty acids, calcium and a variable amount of fibrous connective tissue. The elation between vulnerable plaques and cardiovascular events can be determined using plaque biomarkers. In this work, atherosclerotic plaques stained with different molar ratios of europium, in a potential plaque biomarker, europium tetracycline complex, were studied by fluorescence microscopy. The tetracycline antibiotic used was chlortetracycline. The growth of atherosclerotic plaque was followed during 60 days in New Zealand rabbits divided in two groups: an experimental group (EG), with nine animals and a control group (CG) with three animals. The animals in the EG received a diet with 1% of cholesterol and the animals of GC received a normal diet. The aortic arch of the animals with 60 days were cut in the vertical plane in 6 μm thick slices, which were mounted on glass slides and stained with hematoxylin an eosin and europium chlortetracycline complex (EuCTc). The fluorescence images were obtained exciting the EuCTc absorption band with a filter cube D (BP 355 - 425) and the emission was collected with a LP 470 suppression filter. Light intensity, detector gain and acquisition time were fixed for comparisons. The 20× magnified images were collected with 12 bit (or 4096 gray tones) resolution. The mean value of gray scale for each molar ratio of EuCTc was different, indicating that the complex interacts with the components of atherosclerotic plaque and the best molar ratio was 1.5 EuCTc. These results indicate the potential use of the EuCTc biomarker for atherosclerotic plaque characterization.

Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients.

Science.gov (United States)

Kolgiri, Vaishali; Patil, Vinayak Wamanrao

The major complications of "treated" Human Immunodeficiency Virus (HIV) infection are cardiovascular disease, malignancy, renal disease, liver disease, bone disease, and perhaps neurological complications, which are phenomena of the normal aging process occurring at an earlier age in the HIV-infected population. The present study is aimed to explore protein carbonyl content as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. To investigate the potential of carbonyl content as a biomarker for detecting oxidative Deoxyribonucleic acid (DNA) damage induced Antiretroviral Theraphy (ART) toxicity and/or accelerated aging in HIV/AIDS patients. In this case-control study a total 600 subjects were included. All subjects were randomly selected and grouped as HIV-negative (control group) (n=300), HIV-infected ART naive (n=100), HIV-infected on first line ART (n=100), and HIV-infected on second line ART (n=100). Seronegative control subjects were age- and sex-matched with the ART naive patients and the two other groups. Carbonyl protein was determined by the method described in Levine et al. DNA damage marker 8-OH-dG was determined using 8-hydroxy-2-deoxy Guanosine StressXpress ELA Kit by StressMarq Biosciences. Protein carbonyl content levels and oxidative DNA damage were significantly higher (paging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients. Copyright © 2016 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

The role of novel biomarkers in predicting diabetic nephropathy: a review

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Uwaezuoke SN

2017-08-01

Full Text Available Samuel N Uwaezuoke Pediatric Nephrology Firm, Department of Pediatrics, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Diabetic nephropathy (DN is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM, and occasionally from type 2 diabetes mellitus (T2DM. Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN. Keywords: type 1 diabetes mellitus, renal microvascular complication, microalbuminuria, end-stage kidney disease, biomarker panel

In situ evaluation of cadmium biomarkers in green algae

Energy Technology Data Exchange (ETDEWEB)

Simon, Dana F.; Davis, Thomas A. [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Tercier-Waeber, Mary-Lou [Analytical and Biophysical Environmental Chemistry, University of Geneva, Sciences II, 30 Quai Ernest-Ansermet, 1211 Geneva 4 (Switzerland); England, Roxane [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada); Wilkinson, Kevin J., E-mail: kj.wilkinson@umontreal.ca [Department of Chemistry, University of Montreal, P.O. Box 6128, Succursale Centre-ville, Montreal, Quebec H3C 3J7 (Canada)

2011-10-15

In situ measurements provide data that are the highly representative of the natural environment. In this paper, laboratory-determined biomarkers of Cd stress that were previously identified for the green alga Chlamydomonas reinhardtii, were tested in two French rivers: a contaminated site on the Riou Mort River and an 'uncontaminated' reference site on the Lot River. Transcript abundance levels were determined by real time qPCR for biomarkers thought to be Cd sensitive. Transcript levels were significantly higher (>5 fold) for organisms exposed to the contaminated site as compared to those exposed at the uncontaminated site. Biomarker mRNA levels were best correlated to free Cd (Cd{sup 2+}) rather than intracellular Cd, suggesting that they may be useful indicators of in situ stress. The paper shows that biomarker expression levels increased with time, were sensitive to metal levels and metal speciation and were higher in the 'contaminated' as opposed to the 'reference' site. - Highlights: > Biomarkers of Cd stress were tested in a contaminated and a reference site. > The organism was viable under exposure conditions and metal accumulation occurred. > Biomarker levels were correlated to Cd{sup 2+} and were higher in the contaminated site. - Algal transcription levels of several biomarkers were studied in two natural waters in situ.

The use of mass spectrometry for analysing metabolite biomarkers in epidemiology

DEFF Research Database (Denmark)

Lind, Mads Vendelbo; Savolainen, Otto I; Ross, Alastair B

2016-01-01

measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many...... biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses...

Biomarkers of Renal Function : Towards Clinical Actionability

NARCIS (Netherlands)

Binnenmars, S Heleen; Hijmans, R S; Navis, G; de Borst, M H

This review provides an overview of the clinical value of themost relevant renal biomarkers, focusing on two main clinical conditions: acute kidney injury and chronic kidney disease. We categorize biomarkers according to their actionability, in terms of a documented response to treatment in relation

Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome

NARCIS (Netherlands)

Krzystek-Korpacka, Malgorzata; Patryn, Eliza; Bednarz-Misa, Iwona; Mierzchala, Magdalena; Hotowy, Katarzyna; Czapinska, Elzbieta; Kustrzeba-Wojcicka, Irena; Gamian, Andrzej; Noczynska, Anna

2011-01-01

Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters

Association between salivary sialic acid and periodontal health status among smokers

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Jwan Ibrahim Jawzali

2016-07-01

Conclusion: Salivary free sialic acid may be used as a diagnostic oxidative stress biomarker for periodontal diseases among young current smokers. Cumulative destructive effect of long duration of smoking on the periodontum can be controlled by smoking cessation, good oral hygiene and diet habit in early old ages.

Biomarker Detection using PS2-Thioaptamers, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — AM Biotechnologies (AM) will develop a system to detect and quantify bone demineralization biomarkers as outlined in SBIR Topic "Technologies to Detect Biomarkers"....

Guidelines for Biomarker of Food Intake Reviews (BFIRev: how to conduct an extensive literature search for biomarker of food intake discovery

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Giulia Praticò

2018-02-01

Full Text Available Abstract Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs. However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Guidelines for Biomarker of Food Intake Reviews (BFIRev): how to conduct an extensive literature search for biomarker of food intake discovery.

Science.gov (United States)

Praticò, Giulia; Gao, Qian; Scalbert, Augustin; Vergères, Guy; Kolehmainen, Marjukka; Manach, Claudine; Brennan, Lorraine; Pedapati, Sri Harsha; Afman, Lydia A; Wishart, David S; Vázquez-Fresno, Rosa; Lacueva, Cristina Andres; Garcia-Aloy, Mar; Verhagen, Hans; Feskens, Edith J M; Dragsted, Lars O

2018-01-01

Identification of new biomarkers of food and nutrient intake has developed fast over the past two decades and could potentially provide important new tools for compliance monitoring and dietary intake assessment in nutrition and health science. In recent years, metabolomics has played an important role in identifying a large number of putative biomarkers of food intake (BFIs). However, the large body of scientific literature on potential BFIs outside the metabolomics area should also be taken into account. In particular, we believe that extensive literature reviews should be conducted and that the quality of all suggested biomarkers should be systematically evaluated. In order to cover the literature on BFIs in the most appropriate and consistent manner, there is a need for appropriate guidelines on this topic. These guidelines should build upon guidelines in related areas of science while targeting the special needs of biomarker methodology. This document provides a guideline for conducting an extensive literature search on BFIs, which will provide the basis to systematically validate BFIs. This procedure will help to prioritize future work on the identification of new potential biomarkers and on validating these as well as other biomarker candidates, thereby providing better tools for future studies in nutrition and health.

Can Biomarkers Help the Early Diagnosis of Parkinson's Disease?

Institute of Scientific and Technical Information of China (English)

Weidong Le; Jie Dong; Song Li; Amos D.Korczyn

2017-01-01

Parkinson's disease (PD) is a complex neurodegenerative disease with progressive loss of dopamine neurons.PD patients usually manifest a series of motor and non-motor symptoms.In order to provide better early diagnosis and subsequent disease-modifying therapies for PD patients,there is an urgent need to identify sensitive and specific biomarkers.Biomarkers can be divided into four categories:clinical,imaging,biochemical,and genetic.Ideal biomarkers not only improve our understanding of PD pathogenesis and progression,but also provide benefits for early risk evaluation and clinical diagnosis of PD.Although many efforts have been made and several biomarkers have been extensively investigated,few if any have been found useful for early diagnosis.Here,we summarize recent developments in the discovered biomarkers of PD and discuss their merits and limitations for the early diagnosis of PD.

Potential Peripheral Biomarkers for the Diagnosis of Alzheimer's Disease

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Seema Patel

2011-01-01

Full Text Available Advances in the discovery of a peripheral biomarker for the diagnosis of Alzheimer's would provide a way to better detect the onset of this debilitating disease in a manner that is both noninvasive and universally available. This paper examines the current approaches that are being used to discover potential biomarker candidates available in the periphery. The search for a peripheral biomarker that could be utilized diagnostically has resulted in an extensive amount of studies that employ several biological approaches, including the assessment of tissues, genomics, proteomics, epigenetics, and metabolomics. Although a definitive biomarker has yet to be confirmed, advances in the understanding of the mechanisms of the disease and major susceptibility factors have been uncovered and reveal promising possibilities for the future discovery of a useful biomarker.

Fatty acid biomarkers: validation of food web and trophic markers using C-13-labelled fatty acids in juvenile sandeel ( Ammodytes tobianus )

DEFF Research Database (Denmark)

Dalsgaard, Anne Johanne Tang; St. John, Michael

2004-01-01

A key issue in marine science is parameterizing trophic interactions in marine food webs, thereby developing an understanding of the importance of top-down and bottom-up controls on populations of key trophic players. This study validates the utility of fatty acid food web and trophic markers usi......), respectively. Lack of temporal trends in nonlabelled fatty acids confirmed the conservative incorporation of labelled fatty acids by the fish.......A key issue in marine science is parameterizing trophic interactions in marine food webs, thereby developing an understanding of the importance of top-down and bottom-up controls on populations of key trophic players. This study validates the utility of fatty acid food web and trophic markers using...... C-13-labelled fatty acids to verify the conservative incorporation of fatty acid tracers by juvenile sandeel (Ammodytes tobianus) and assess their uptake, clearance, and metabolic turnover rates. Juvenile sandeel were fed for 16 days in the laboratory on a formulated diet enriched in (13)C16...

Time-dependent efficacy of longitudinal biomarker for clinical endpoint.

Science.gov (United States)

Kolamunnage-Dona, Ruwanthi; Williamson, Paula R

2018-06-01

Joint modelling of longitudinal biomarker and event-time processes has gained its popularity in recent years as they yield more accurate and precise estimates. Considering this modelling framework, a new methodology for evaluating the time-dependent efficacy of a longitudinal biomarker for clinical endpoint is proposed in this article. In particular, the proposed model assesses how well longitudinally repeated measurements of a biomarker over various time periods (0,t) distinguish between individuals who developed the disease by time t and individuals who remain disease-free beyond time t. The receiver operating characteristic curve is used to provide the corresponding efficacy summaries at various t based on the association between longitudinal biomarker trajectory and risk of clinical endpoint prior to each time point. The model also allows detecting the time period over which a biomarker should be monitored for its best discriminatory value. The proposed approach is evaluated through simulation and illustrated on the motivating dataset from a prospective observational study of biomarkers to diagnose the onset of sepsis.

Mass spectrometry-based proteomic quest for diabetes biomarkers.

Science.gov (United States)

Shao, Shiying; Guo, Tiannan; Aebersold, Ruedi

2015-06-01

Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia, which affects hundreds of millions of individuals worldwide. Early diagnosis and complication prevention of DM are helpful for disease treatment. However, currently available DM diagnostic markers fail to achieve the goals. Identification of new diabetic biomarkers assisted by mass spectrometry (MS)-based proteomics may offer solution for the clinical challenges. Here, we review the current status of biomarker discovery in DM, and describe the pressure cycling technology (PCT)-Sequential Window Acquisition of all Theoretical fragment-ion (SWATH) workflow for sample-processing, biomarker discovery and validation, which may accelerate the current quest for DM biomarkers. This article is part of a Special Issue entitled: Medical Proteomics. Copyright © 2014 Elsevier B.V. All rights reserved.

Stable isotopes and biomarkers in microbial ecology

NARCIS (Netherlands)

Boschker, H.T.S.; Middelburg, J.J.

2002-01-01

The use of biomarkers in combination with stable isotope analysis is a new approach in microbial ecology and a number of papers on a variety of subjects have appeared. We will first discuss the techniques for analysing stable isotopes in biomarkers, primarily gas chromatography-combustion-isotope

Bias in emerging biomarkers for bipolar disorder

DEFF Research Database (Denmark)

Carvalho, A F; Köhler, C A; Fernandes, B S

2016-01-01

BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, E...

Biomarkers in critical illness: have we made progress?

Directory of Open Access Journals (Sweden)

Honore PM

2016-10-01

Full Text Available Patrick M Honore,1 Rita Jacobs,1 Inne Hendrickx,1 Elisabeth De Waele,1 Viola Van Gorp,1 Olivier Joannes-Boyau,2 Jouke De Regt,1 Willem Boer,3 Herbert D Spapen1 1Intensive Care Unit, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium; 2Intensive Care Unit, Hopital Haut Leveque, University of Bordeaux 2, Bordeaux, France; 3Intensive Care Unit, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Biomarkers have emerged as exemplary key players in translational medicine. Many have been assessed for timely recognition, early treatment, and adequate follow-up for a variety of pathologies. Biomarker sensitivity has improved considerably over the last years but specificity remains poor, in particular when two “marker-sensitive” conditions overlap in one patient. Biomarker research holds an enormous potential for diagnostic and prognostic purposes in postoperative and critically ill patients who present varying degrees of inflammation, infection, and concomitant (subacute organ dysfunction or failure. Despite a remarkable progress in development and testing, biomarkers are not yet ready for routine use at the bedside. Keywords: biomarkers, acute kidney injury, sepsis, ARDS

Clinical, functional, behavioural and epigenomic biomarkers of obesity.

Science.gov (United States)

Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

2017-06-01

Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yu [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang R & D Center for Food Technology and Equipment, Fuli Institute of Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Wang, Qiao; Cheng, Jun [Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang (China); Zhang, Jingshun; Xu, Jiaojiao [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China); Ren, Yiping, E-mail: renyiping@263.net [Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, Zhejiang (China)

2015-09-24

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry

International Nuclear Information System (INIS)

Zhang, Yu; Wang, Qiao; Cheng, Jun; Zhang, Jingshun; Xu, Jiaojiao; Ren, Yiping

2015-01-01

Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1–0.3 ng/mL and 0.4–1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%–105.4%, 98.2%–114.0% and 92.2%–108.9%, respectively. Acceptable within-laboratory reproducibility (RSD < 7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive

Clinical Relevance of Biomarkers of Oxidative Stress

DEFF Research Database (Denmark)

Frijhoff, Jeroen; Winyard, Paul G; Zarkovic, Neven

2015-01-01

SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino ac....... The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker.......SIGNIFICANCE: Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino...... acids. RECENT ADVANCES: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES: The literature is very heterogeneous...

Oral Metagenomic Biomarkers in Rheumatoid Arthritis

Science.gov (United States)

2017-09-01

individuals with rheumatoid arthritis (RA). The goal is to test the  hypothesis that oral microbiome and metagenomic analyses will allow  us  to identify new...biomarkers  that are  useful  for the diagnosis of early RA and/or biomarkers that help to predict the efficacy of  specific therapeutic interventions... RNA  microbiome analysis as well as whole genome shotgun sequencing.  Upon completion of these aims, any identified bacterial biomarkers may be

The use of biomarkers in occupational health research, practice, and policy.

Science.gov (United States)

Schulte, P A; Hauser, J E

2012-08-13

Biomarkers are potentially useful tools for occupational health and safety research, practice, and policy. However, the full realization of this potential has not been achieved. In this paper, the progress made in these three usage areas is reviewed to identify what efforts can be taken to realize the full promise of biomarkers. Biomarker uses are described by a diverse taxonomy that builds on the categories of exposure, effect and susceptibility, and the continuum between exposure and disease prognosis. The most significant uses of biomarkers in occupational health have been in biological monitoring of workers. Other important uses have been in enhancing research and assessing mechanisms of action of occupational toxicants at low exposures. Seven critical areas will influence the extent to which the potential of biomarkers in occupational health and safety is realized. These include: (1) adequate investment in validation; (2) obtaining international agreement on exposure guidelines; (3) exploring the utility of biomarkers in regulation; (4) applying biomarkers to critical occupational safety and health questions; (5) developing the exposome; (6) utilizing biomarkers to address emerging occupational health issues; and (7) continuing to address the ethical and social justice issues related to biomarkers. Overall, if biomarkers are to make a major contribution to occupational health and safety then a more holistic approach to bringing them from the laboratory to practice will be needed. Published by Elsevier Ireland Ltd.

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Science.gov (United States)

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

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Ranjit Chauhan

2016-01-01

Full Text Available 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.

Novel ageing-biomarker discovery using data-intensive technologies.

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Griffiths, H R; Augustyniak, E M; Bennett, S J; Debacq-Chainiaux, F; Dunston, C R; Kristensen, P; Melchjorsen, C J; Navarrete, Santos A; Simm, A; Toussaint, O

2015-11-01

Ageing is accompanied by many visible characteristics. Other biological and physiological markers are also well-described e.g. loss of circulating sex hormones and increased inflammatory cytokines. Biomarkers for healthy ageing studies are presently predicated on existing knowledge of ageing traits. The increasing availability of data-intensive methods enables deep-analysis of biological samples for novel biomarkers. We have adopted two discrete approaches in MARK-AGE Work Package 7 for biomarker discovery; (1) microarray analyses and/or proteomics in cell systems e.g. endothelial progenitor cells or T cell ageing including a stress model; and (2) investigation of cellular material and plasma directly from tightly-defined proband subsets of different ages using proteomic, transcriptomic and miR array. The first approach provided longitudinal insight into endothelial progenitor and T cell ageing. This review describes the strategy and use of hypothesis-free, data-intensive approaches to explore cellular proteins, miR, mRNA and plasma proteins as healthy ageing biomarkers, using ageing models and directly within samples from adults of different ages. It considers the challenges associated with integrating multiple models and pilot studies as rational biomarkers for a large cohort study. From this approach, a number of high-throughput methods were developed to evaluate novel, putative biomarkers of ageing in the MARK-AGE cohort. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

The Role of Sarcosine, Uracil, and Kynurenic Acid Metabolism in Urine for Diagnosis and Progression Monitoring of Prostate Cancer

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Georgios Gkotsos

2017-02-01

Full Text Available The aim of this pilot study is to evaluate sarcosine, uracil, and kynurenic acid in urine as potential biomarkers in prostate cancer detection and progression monitoring. Sarcosine, uracil, and kynurenic acid were measured in urine samples of 32 prostate cancer patients prior to radical prostatectomy, 101 patients with increased prostate-specific antigen prior to ultrasonographically-guided prostatic biopsy collected before and after prostatic massage, and 15 healthy volunteers (controls. The results were related to histopathologic data, Gleason score, and PSA (Prostate Specific Antigen. Metabolites were measured after analysis of urine samples with Ultra-High Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS instrumentation. Multivariate, nonparametric statistical tests including receiver operating characteristics analyses, one-way analysis of variance (Kruskal–Wallis test, parametric statistical analysis, and Pearson correlation, were performed to evaluate diagnostic performance. Decreased median sarcosine and kynurenic acid and increased uracil concentrations were observed for patients with prostate cancer compared to participants without malignancy. Results showed that there was no correlation between the concentration of the studied metabolites and the cancer grade (Gleason score <7 vs. ≥7 and the age of the patients. Evaluation of biomarkers by ROC (Receiving Operating Characteristics curve analysis showed that differentiation of prostate cancer patients from participants without malignancy was not enhanced by sarcosine or uracil levels in urine. In contrast to total PSA values, kynurenic acid was found a promising biomarker for the detection of prostate cancer particularly in cases where collection of urine samples was performed after prostatic massage. Sarcosine and uracil in urine samples of patients with prostate cancer were not found as significant biomarkers for the diagnosis of prostate cancer

Biomarkers of nanomaterial exposure and effect: current status

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Iavicoli, Ivo; Leso, Veruscka; Manno, Maurizio; Schulte, Paul A.

2014-03-01

Recent advances in nanotechnology have induced a widespread production and application of nanomaterials. As a consequence, an increasing number of workers are expected to undergo exposure to these xenobiotics, while the possible hazards to their health remain not being completely understood. In this context, biological monitoring may play a key role not only to identify potential hazards from and to evaluate occupational exposure to nanomaterials, but also to detect their early biological effects to better assess and manage risks of exposure in respect of the health of workers. Therefore, the aim of this review is to provide a critical evaluation of potential biomarkers of nanomaterial exposure and effect investigated in human and animal studies. Concerning exposure biomarkers, internal dose of metallic or metal oxide nanoparticle exposure may be assessed measuring the elemental metallic content in blood or urine or other biological materials, whereas specific molecules may be carefully evaluated in target tissues as possible biomarkers of biologically effective dose. Oxidative stress biomarkers, such as 8-hydroxy-deoxy-guanosine, genotoxicity biomarkers, and inflammatory response indicators may also be useful, although not specific, as biomarkers of nanomaterial early adverse health effects. Finally, potential biomarkers from "omic" technologies appear to be quite innovative and greatly relevant, although mechanistic, ethical, and practical issues should all be resolved before their routine application in occupational settings could be implemented. Although all these findings are interesting, they point out the need for further research to identify and possibly validate sensitive and specific biomarkers of exposure and effect, suitable for future use in occupational biomonitoring programs. A valuable contribution may derive from the studies investigating the biological behavior of nanomaterials and the factors influencing their toxicokinetics and reactivity. In

Hybrid inorganic/organic photonic crystal biochips for cancer biomarkers detection

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Sinibaldi, Alberto; Danz, Norbert; Munzert, Peter; Michelotti, Francesco

2018-06-01

We report on hybrid inorganic/organic one-dimensional photonic crystal biochips sustaining Bloch surface waves. The biochips were used, together with an optical platform operating in a label-free and fluorescence configuration simultaneously, to detect the cancer biomarker Angiopoietin 2 in a protein base buffer. The hybrid photonic crystals embed in their geometry a thin functionalization poly-acrylic acid layer deposited by plasma polymerization, which is used to immobilize a monoclonal antibody for highly specific biological recognition. The fluorescence operation mode is described in detail, putting into evidence the role of field enhancement and localization at the photonic crystal surface in the shaping and intensification of the angular fluorescence pattern. In the fluorescence operation mode, the hybrid biochips can attain the limit of detection 6 ng/ml.

Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry.

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Lee, Jung-Eun; Lee, Yu Ho; Kim, Se-Yun; Kim, Yang Gyun; Moon, Ju-Young; Jeong, Kyung-Hwan; Lee, Tae Won; Ihm, Chun-Gyoo; Kim, Sooah; Kim, Kyoung Heon; Kim, Dong Ki; Kim, Yon Su; Kim, Chan-Duck; Park, Cheol Whee; Lee, Do Yup; Lee, Sang-Ho

2016-07-01

The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represented by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous glomerulonephritis (MGN). Since urine metabolites may mirror disease-specific functional perturbations in kidney injury, we examined urine samples for distinctive metabolic changes to identify biomarkers for clinical applications. We developed unbiased multi-component covarianced models from a discovery set with 48 samples (12 healthy controls, 12 MCD, 12 FSGS, and 12 MGN). To extensively validate their diagnostic potential, new batch from 54 patients with primary NS were independently examined a year after. In the independent validation set, the model including citric acid, pyruvic acid, fructose, ethanolamine, and cysteine effectively discriminated each NS using receiver operating characteristic (ROC) analysis except MCD-MGN comparison; nonetheless an additional metabolite multi-composite greatly improved the discrimination power between MCD and MGN. Finally, we proposed the re-constructed metabolic network distinctively dysregulated by the different NSs that may deepen comprehensive understanding of the disease mechanistic, and help the enhanced identification of NS and therapeutic plans for future. Copyright © 2016 Elsevier B.V. All rights reserved.

YKL-40: a new biomarker in cardiovascular disease?

DEFF Research Database (Denmark)

Mathiasen, Anders Bruun; Henningsen, Kristoffer Mads Aaris; Harutyunyan, Marina Jurjevna

2010-01-01

Cardiovascular disease in the form of coronary artery disease is the most common cause of death in western countries. Early treatment with stabilizing drugs and mechanical revascularization by percutaneous coronary intervention or coronary bypass surgery has reduced the mortality significantly....... But in spite of improved treatments, many patients are still plagued by a high frequency of angina symptoms, hospitalizations and a poor prognosis. There is a need for new independent or supplementary biomarkers that can help to predict cardiovascular disease and cardiovascular events earlier and more...... precisely, and thus accompany existing biomarkers in both primary and secondary cardiovascular prevention. One such potential new biomarker is the protein YKL-40. As an independent biomarker in both cardiovascular diseases and noncardiovascular diseases, current evidence suggests YKL-40 to be most useful...

Telomere Length – a New Biomarker in Medicine

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Agnieszka Kozłowska

2015-12-01

Full Text Available A number of xenobiotics in the environment and workplace influences on our health and life. Biomarkers are tools for measuring such exposures and their effects in the organism. Nowadays, telomere length, epigenetic changes, mutations and changes in gene expression pattern have become new molecular biomarkers. Telomeres play the role of molecular clock, which influences on expectancy of cell life and thus aging, the formation of damages, development diseases and carcinogenesis. The telomere length depends on mechanisms of replication and the activity of telomerase. Telomere length is currently used as a biomarker of susceptibility and/or exposure. This paper describes the role of telomere length as a biomarker of aging cells, oxidative stress, a marker of many diseases including cancer, and as a marker of environmental and occupational exposure.

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

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Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-03-01

Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

The Wide and Complex Field of NAFLD Biomarker Research: Trends.

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Wichro, Erika; Macheiner, Tanja; Schmid, Jasmin; Kavsek, Barbara; Sargsyan, Karine

2014-01-01

Background. Nonalcoholic fatty liver disease is now acknowledged as a complex public health issue linked to sedentary lifestyle, obesity, and related disorders like type 2 diabetes and metabolic syndrome. Aims. We aimed to retrieve its trends out of the huge amount of published data. Therefore, we conducted an extensive literature search to identify possible biomarker and/or biomarker combinations by retrospectively assessing and evaluating common and novel biomarkers to predict progression and prognosis of obesity related liver diseases. Methodology. We analyzed finally 62 articles accounting for 157 cohorts and 45,288 subjects. Results. Despite the various approaches, most cohorts were considerably small and rarely comparable. Also, we found that the same standard parameters were measured rather than novel biomarkers. Diagnostics approaches appeared incomparable. Conclusions. Further collaborative investigations on harmonizing ways of data acquisition and identifying such biomarkers for clinical use are necessary to yield sufficient significant results of potential biomarkers.

A brief review and evaluation of earthworm biomarkers in soil pollution assessment.

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Shi, Zhiming; Tang, Zhiwen; Wang, Congying

2017-05-01

Earthworm biomarker response to pollutants has been widely investigated in the assessment of soil pollution. However, whether and how the earthworm biomarker-approach can be actually applied to soil pollution assessment is still a controversial issue. This review is concerned about the following points: 1. Despite much debate, biomarker is valuable to ecotoxicology and biomarker approach has been properly used in different fields. Earthworm biomarker might be used in different scenarios such as large-scale soil pollution survey and soil pollution risk assessment. Compared with physicochemical analysis, they can provide more comprehensive and straightforward information about soil pollution at low cost. 2. Although many earthworm species from different ecological categories have been tested, Eisenia fetida/andrei is commonly used. Many earthworm biomarkers have been screened from the molecular to the individual level, while only a few biomarkers, such as avoidance behavior and lysosomal membrane stability, have been focused on. Other aspects of the experimental design were critically reviewed. 3. More studies should focus on determining the reliability of various earthworm biomarkers in soil pollution assessment in future research. Besides, establishing a database of a basal level of each biomarker, exploring biomarker response in different region/section/part of earthworm, and other issues are also proposed. 4. A set of research guideline for earthworm biomarker studies was recommended, and the suitability of several earthworm biomarkers was briefly evaluated with respect to their application in soil pollution assessment. This review will help to promote further studies and practical application of earthworm biomarker in soil pollution assessment.

The economics of cardiac biomarker testing in suspected myocardial infarction.

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Goodacre, Steve; Thokala, Praveen

2015-03-01

Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Combined quantification of faecal sterols, stanols, stanones and bile acids in soils and terrestrial sediments by gas chromatography-mass spectrometry.

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Birk, Jago Jonathan; Dippold, Michaela; Wiesenberg, Guido L B; Glaser, Bruno

2012-06-15

Faeces incorporation can alter the concentration patterns of stanols, stanones, Δ(5)-sterols and bile acids in soils and terrestrial sediments. A joint quantification of these substances would give robust and specific information about the faecal input. Therefore, a method was developed for their purification and determination via gas chromatography-mass spectrometry (GC-MS) based on a total lipid extract (TLE) of soils and terrestrial sediments. Stanols, stanones, Δ(5)-steroles and bile acids were extracted by a single Soxhlet extraction yielding a TLE. The TLE was saponified with KOH in methanol. Sequential liquid-liquid extraction was applied to recover the biomarkers from the saponified extract and to separate the bile acids from the neutral stanoles, stanones and Δ(5)-steroles. The neutral fraction was directly purified using solid phase extraction (SPE) columns packed with 5% deactivated silica gel. The bile acids were methylated in dry HCl in methanol and purified on SPE columns packed with activated silica gel. A mixture of hexamethyldisilazane (HMDS), trimethylchlorosilane (TMCS) and pyridine was used to silylate the hydroxyl groups of the stanols and Δ(5)-sterols avoiding a silylation of the keto groups of the stanones in their enol-form. Silylation of the bile acids was carried out with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) containing N-trimethylsilylimidazole (TSIM). TLEs from a set of soils with different physico-chemical properties were used for method evaluation and for comparison of amounts of faecal biomarkers analysed with saponification and without saponification of the TLE. Therefore, a Regosol, a Podzol and a Ferralsol were sampled. To proof the applicability of the method for faecal biomarker analyses in archaeological soils and sediments, additional samples were taken from pre-Columbian Anthrosols in Amazonia and an Anthrosol from a site in central Europe settled since the Neolithic. The comparison of the amounts of steroids

Molecularly imprinted polyaniline-ferrocene-sulfonic acid-Carbon dots modified pencil graphite electrodes for chiral selective sensing of D-Ascorbic acid and L-Ascorbic acid: A clinical biomarker for preeclampsia

International Nuclear Information System (INIS)

Pandey, Indu; Jha, Shashank Shekhar

2015-01-01

Highlights: • Pencil graphite electrode was non-covalently functionalized by C-dots. • Electrochemically synthesized ferrocene-sulfonic acid doped PANI film was used as chiral recognition element. • Electrochemical chiral sensing of L-ascorbic acid and D-ascorbic acid was carried out. • L-ascorbic acid determination was done in aqueous, biological and pharmaceutical samples at nM level. - Abstract: A simple and novel method is proposed for chiral separation of L-ascorbic acid and D-ascorbic acid in human cerebrospinal fluids and blood plasma samples. Electro-polymerized molecularly imprinted poly-aniline ferrocenesulfonic acid-C-dots modified pencil graphite electrodes was successfully applied for separation and quantification of D-/L-ascorbic acid in aqueous and some biological samples. Parameters, important to control the performance of the electrochemical sensor were investigated and optimized, including the effects of pH, monomer- template ratios, electropolymerization cycles and scan rates. The molecularly imprinted film exhibited a high chiral selectivity and sensitivity towards D-ascorbic acid and L-ascorbic acid respectively. The surface morphologies and electrochemical properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry, chrono-amperometry and electrochemical impedance spectroscopy. L-ascorbic acid selective sensor shows excellent selectivity towards the L-ascorbic acid in comparison to D- ascorbic acid vice versa for D- ascorbic acid selective sensor. Under optimal conditions the linear range of the calibration curve for L- ascorbic acid and D- ascorbic acid was 6.0–165.0 nM and 6.0–155.0 nM, with the detection limit of 0.001 nM and 0.002 nM. Chiral detection of L-ascorbic acid was successfully carried out in pharmaceuticals and human plasma samples (pregnant women and non pregnant women) via proposed sensor with good selectivity and sensitivity.

Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador.

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Iannotti, Lora L; Lutter, Chessa K; Waters, William F; Gallegos Riofrío, Carlos Andres; Malo, Carla; Reinhart, Gregory; Palacios, Ana; Karp, Celia; Chapnick, Melissa; Cox, Katherine; Aguirre, Santiago; Narvaez, Luis; López, Fernando; Sidhu, Rohini; Kell, Pamela; Jiang, Xuntian; Fujiwara, Hideji; Ory, Daniel S; Young, Rebecca; Stewart, Christine P

2017-12-01

Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63. Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids. Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6-9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine- N -oxide (TMAO) with the use of liquid chromatography-tandem mass spectrometry. Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA. Conclusion: The findings supported our hypothesis that early introduction of eggs significantly

Inferring Phytoplankton, Terrestrial Plant and Bacteria Bulk δ¹³C Values from Compound Specific Analyses of Lipids and Fatty Acids

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Taipale, Sami J.; Peltomaa, Elina; Hiltunen, Minna; Jones, Roger I.; Hahn, Martin W.; Biasi, Christina; Brett, Michael T.

2015-01-01

Stable isotope mixing models in aquatic ecology require δ13C values for food web end members such as phytoplankton and bacteria, however it is rarely possible to measure these directly. Hence there is a critical need for improved methods for estimating the δ13C ratios of phytoplankton, bacteria and terrestrial detritus from within mixed seston. We determined the δ13C values of lipids, phospholipids and biomarker fatty acids and used these to calculate isotopic differences compared to the whole-cell δ13C values for eight phytoplankton classes, five bacterial taxa, and three types of terrestrial organic matter (two trees and one grass). The lipid content was higher amongst the phytoplankton (9.5±4.0%) than bacteria (7.3±0.8%) or terrestrial matter (3.9±1.7%). Our measurements revealed that the δ13C values of lipids followed phylogenetic classification among phytoplankton (78.2% of variance was explained by class), bacteria and terrestrial matter, and there was a strong correlation between the δ13C values of total lipids, phospholipids and individual fatty acids. Amongst the phytoplankton, the isotopic difference between biomarker fatty acids and bulk biomass averaged -10.7±1.1‰ for Chlorophyceae and Cyanophyceae, and -6.1±1.7‰ for Cryptophyceae, Chrysophyceae and Diatomophyceae. For heterotrophic bacteria and for type I and type II methane-oxidizing bacteria our results showed a -1.3±1.3‰, -8.0±4.4‰, and -3.4±1.4‰ δ13C difference, respectively, between biomarker fatty acids and bulk biomass. For terrestrial matter the isotopic difference averaged -6.6±1.2‰. Based on these results, the δ13C values of total lipids and biomarker fatty acids can be used to determine the δ13C values of bulk phytoplankton, bacteria or terrestrial matter with ± 1.4‰ uncertainty (i.e., the pooled SD of the isotopic difference for all samples). We conclude that when compound-specific stable isotope analyses become more widely available, the determination of �

Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

Science.gov (United States)

Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

2018-05-02

The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

Biomarkers in the Diagnosis and Prognosis of Alzheimer's Disease.

Science.gov (United States)

Schaffer, Cole; Sarad, Nakia; DeCrumpe, Ashton; Goswami, Disha; Herrmann, Sara; Morales, Jose; Patel, Parth; Osborne, Jim

2015-10-01

Alzheimer's disease (AD) is a neurodegenerative disease that inhibits cognitive functions and has no cure. This report reviews the current diagnostic standards for AD with an emphasis on early diagnosis using the cerebrospinal fluid (CSF) biomarkers amyloid-beta, t-tau, and p-tau and fluorodeoxyglucose positron emission tomography imaging. Abnormal levels of these CSF biomarkers and decreased cerebral uptake of glucose have recently been used in the early diagnosis of AD in experimental studies. These promising biomarkers can be measured using immunoassays performed in singleplex or multiplex formats. Although presently, there are no Food and Drug Administration-approved in vitro diagnostics (IVDs) for early detection of AD, a multiplex immunoassay measuring a panel of promising AD biomarkers in CSF may be a likely IVD candidate for the clinical AD diagnostic market. Specifically, the INNO-BIA AlzBio3 immunoassay kit, performed using bead arrays on the xMAP Luminex analyzer, allows simultaneous quantification of amyloid-beta, t-tau, and p-tau biomarkers. AD biomarkers can also be screened using enzyme-linked immunosorbent assays that are offered as laboratory-developed tests. © 2014 Society for Laboratory Automation and Screening.

Potential biomarkers for bipolar disorder: Where do we stand?

Directory of Open Access Journals (Sweden)

Rajesh Sagar

2017-01-01

Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

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

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Szederjesi Janos

2015-10-01

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

Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

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Chen, Rui; Han, Su; Liu, Xuefeng; Wang, Kunpeng; Zhou, Yong; Yang, Chundong; Zhang, Xi

2018-05-15

Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. Copyright © 2018 Elsevier B.V. All rights reserved.

Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

International Nuclear Information System (INIS)

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

(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 high risk population of cirrhotic patients.

Utilization of metabolomics to identify serum biomarkers for hepatocellular carcinoma in patients with liver cirrhosis

Energy Technology Data Exchange (ETDEWEB)

Ressom, Habtom W., E-mail: hwr@georgetown.edu [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); 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. [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Tadesse, Mahlet G. [Department of Mathematics and Statistics, Georgetown University, Washington, DC 20057 (United States); Goldman, Radoslav [Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 (United States); Shetty, Kirti [Department of Surgery, Georgetown University Medical Center, Washington, DC 20057 (United States); Georgetown University Hospital, Washington, DC 20057 (United States)

2012-09-19

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 high risk population of cirrhotic patients.

Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

Directory of Open Access Journals (Sweden)

Bas C T van Bussel

Full Text Available BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574, by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD and single-biomarker techniques (ELISA or immunoturbidimetric assay, the following biomarkers of low-grade inflammation: C-reactive protein (CRP, serum amyloid A (SAA, soluble intercellular adhesion molecule 1 (sICAM-1 and soluble vascular cell adhesion molecule 1 (sVCAM-1. These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755 absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP, 0.711 (SAA, 0.895 (sICAM-1 and 0.858 (sVCAM-1. Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

Identification of cancer protein biomarkers using proteomic techniques

Energy Technology Data Exchange (ETDEWEB)

Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia

2016-10-18

The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

Tracking Biocultural Pathways to Health Disparities: The Value of Biomarkers

Science.gov (United States)

Worthman, Carol M.; Costello, E. Jane

2009-01-01

Background Cultural factors and biomarkers are emerging emphases in social epidemiology that readily ally with human biology and anthropology. Persistent health challenges and disparities have established biocultural roots, and environment plays an integral role in physical development and function that form the bases of population health. Biomarkers have proven to be valuable tools for investigating biocultural bases of health disparities. Aims We apply recent insights from biology to consider how culture gets under the skin and evaluate the construct of embodiment. We analyze contrasting biomarker models and applications, and propose an integrated model for biomarkers. Three examples from the Great Smoky Mountains Study (GSMS) illustrate these points. Subjects and methods The longitudinal developmental epidemiological GSMS comprises a population-based sample of 1420 children with repeated measures including mental and physical health, life events, household conditions, and biomarkers for pubertal development and allostatic load. Results Analyses using biomarkers resolved competing explanations for links between puberty and depression, identified gender differences in stress at puberty, and revealed interactive effects of birthweight and postnatal adversity on risk for depression at puberty in girls. Conclusion An integrated biomarker model can both enrich epidemiology and illuminate biocultural pathways in population health. PMID:19381986

Scrutinizing the Biomarkers for the Neglected Chagas Disease: How Remarkable!

Science.gov (United States)

Pinho, Rosa T; Waghabi, Mariana C; Cardillo, Fabíola; Mengel, José; Antas, Paulo R Z

2016-01-01

Biomarkers or biosignature profiles have become accessible over time in population-based studies for Chagas disease. Thus, the identification of consistent and reliable indicators of the diagnosis and prognosis of patients with heart failure might facilitate the prioritization of therapeutic management to those with the highest chance of contracting this disease. The purpose of this paper is to review the recent state and the upcoming trends in biomarkers for human Chagas disease. As an emerging concept, we propose a classification of biomarkers based on plasmatic-, phenotype-, antigenic-, genetic-, and management-related candidates. The available data revisited here reveal the lessons learned thus far and the existing challenges that still lie ahead to enable biomarkers to be employed consistently in risk evaluation for this disease. There is a strong need for biomarker validation, particularly for biomarkers that are specific to the clinical forms of Chagas disease. The current failure to achieve the eradication of the transmission of this disease has produced determination to solve this validation issue. Finally, it would be strategic to develop a wide variety of biomarkers and to test them in both preclinical and clinical trials.

Plasma biomarker of dietary phytosterol intake.

Directory of Open Access Journals (Sweden)

Xiaobo Lin

Full Text Available Dietary phytosterols, plant sterols structurally similar to cholesterol, reduce intestinal cholesterol absorption and have many other potentially beneficial biological effects in humans. Due to limited information on phytosterol levels in foods, however, it is difficult to quantify habitual dietary phytosterol intake (DPI. Therefore, we sought to identify a plasma biomarker of DPI.Data were analyzed from two feeding studies with a total of 38 subjects during 94 dietary periods. DPI was carefully controlled at low, intermediate, and high levels. Plasma levels of phytosterols and cholesterol metabolites were assessed at the end of each diet period. Based on simple ordinary least squares regression analysis, the best biomarker for DPI was the ratio of plasma campesterol to the endogenous cholesterol metabolite 5-α-cholestanol (R2 = 0.785, P 0.600; P < 0.01.The ratio of plasma campesterol to the coordinately regulated endogenous cholesterol metabolite 5-α-cholestanol is a biomarker of dietary phytosterol intake. Conversely, plasma phytosterol levels alone are not ideal biomarkers of DPI because they are confounded by large inter-individual variation in absorption and turnover of non-cholesterol sterols. Further work is needed to assess the relation between non-cholesterol sterol metabolism and associated cholesterol transport in the genesis of coronary heart disease.

Imaging biomarkers in primary brain tumours

Energy Technology Data Exchange (ETDEWEB)

Lopci, Egesta; Chiti, Arturo [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Franzese, Ciro; Navarria, Pierina; Scorsetti, Marta [Humanitas Clinical and Research Center, Radiosurgery and Radiotherapy, Rozzano, MI (Italy); Grimaldi, Marco [Humanitas Clinical and Research Center, Radiology, Rozzano, MI (Italy); Zucali, Paolo Andrea; Simonelli, Matteo [Humanitas Clinical and Research Center, Medical Oncology, Rozzano, MI (Italy); Bello, Lorenzo [Humanitas Clinical and Research Center, Neurosurgery, Rozzano, MI (Italy)

2015-04-01

We are getting used to referring to instrumentally detectable biological features in medical language as ''imaging biomarkers''. These two terms combined reflect the evolution of medical imaging during recent decades, and conceptually comprise the principle of noninvasive detection of internal processes that can become targets for supplementary therapeutic strategies. These targets in oncology include those biological pathways that are associated with several tumour features including independence from growth and growth-inhibitory signals, avoidance of apoptosis and immune system control, unlimited potential for replication, self-sufficiency in vascular supply and neoangiogenesis, acquired tissue invasiveness and metastatic diffusion. Concerning brain tumours, there have been major improvements in neurosurgical techniques and radiotherapy planning, and developments of novel target drugs, thus increasing the need for reproducible, noninvasive, quantitative imaging biomarkers. However, in this context, conventional radiological criteria may be inappropriate to determine the best therapeutic option and subsequently to assess response to therapy. Integration of molecular imaging for the evaluation of brain tumours has for this reason become necessary, and an important role in this setting is played by imaging biomarkers in PET and MRI. In the current review, we describe most relevant techniques and biomarkers used for imaging primary brain tumours in clinical practice, and discuss potential future developments from the experimental context. (orig.)

Comparative analysis of selected exhaled breath biomarkers obtained with two different temperature-controlled devices

Directory of Open Access Journals (Sweden)

Brüning Thomas

2009-11-01

Full Text Available Abstract Background The collection of exhaled breath condensate (EBC is a suitable and non-invasive method for evaluation of airway inflammation. Several studies indicate that the composition of the condensate and the recovery of biomarkers are affected by physical characteristics of the condensing device and collecting circumstances. Additionally, there is an apparent influence of the condensing temperature, and often the level of detection of the assay is a limiting factor. The ECoScreen2 device is a new, partly single-use disposable system designed for studying different lung compartments. Methods EBC samples were collected from 16 healthy non-smokers by using the two commercially available devices ECoScreen2 and ECoScreen at a controlled temperature of -20°C. EBC volume, pH, NOx, LTB4, PGE2, 8-isoprostane and cys-LTs were determined. Results EBC collected with ECoScreen2 was less acidic compared to ECoScreen. ECoScreen2 was superior concerning condensate volume and detection of biomarkers, as more samples were above the detection limit (LTB4 and PGE2 or showed higher concentrations (8-isoprostane. However, NOx was detected only in EBC sampled by ECoScreen. Conclusion ECoScreen2 in combination with mediator specific enzyme immunoassays may be suitable for measurement of different biomarkers. Using this equipment, patterns of markers can be assessed that are likely to reflect the complex pathophysiological processes in inflammatory respiratory disease.

Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen

Energy Technology Data Exchange (ETDEWEB)

Milan, Massimo; Pauletto, Marianna; Patarnello, Tomaso; Bargelloni, Luca [Department of Comparative Biomedicine and Food Science, University of Padova, Viale dell' Universita 16, Legnaro (Padova) (Italy); Marin, Maria Gabriella [Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova (Italy); Matozzo, Valerio, E-mail: matozzo@bio.unipd.it [Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova (Italy)

2013-01-15

Pharmaceuticals are a class of emerging environmental contaminants that continuously enter aquatic environments. Presently, little information is available about the effects of these substances on non-target organisms, such as bivalves. We investigated the effects of ibuprofen (IBU) on the clam Ruditapes philippinarum. Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000 {mu}g IBU/L, and established biomarker responses (haemolymph lysozyme, gill acetylcholinesterase and digestive gland superoxide dismutase activities) as well as digestive gland transcriptome were evaluated. A two-way ANOVA revealed significant effects of both 'IBU concentration' and 'exposure duration' on biomarker responses. Overall, the enzyme activities were generally lower in IBU-exposed clams than in controls. Although limited knowledge of the mollusc transcriptome makes it difficult to interpret the effects of IBU on clams, the gene transcription analysis using DNA microarrays enabled the identification of the putative molecular mode of action of the IBU. The functional analysis of differentially transcribed genes suggests that IBU can interfere with various signalling pathways in clams, such as arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B. In addition, several genes involved in the metabolism of xenobiotics (e.g., glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to be significantly affected by IBU exposure. In summary, the integrated approach of gene transcription analysis and biomarker responses facilitated the elucidation of the putative mechanisms of action of IBU in non-target species.

Gene transcription and biomarker responses in the clam Ruditapes philippinarum after exposure to ibuprofen

International Nuclear Information System (INIS)

Milan, Massimo; Pauletto, Marianna; Patarnello, Tomaso; Bargelloni, Luca; Marin, Maria Gabriella; Matozzo, Valerio

2013-01-01

Pharmaceuticals are a class of emerging environmental contaminants that continuously enter aquatic environments. Presently, little information is available about the effects of these substances on non-target organisms, such as bivalves. We investigated the effects of ibuprofen (IBU) on the clam Ruditapes philippinarum. Clams were exposed for 1, 3, 5 and 7 days to 0, 100 and 1000 μg IBU/L, and established biomarker responses (haemolymph lysozyme, gill acetylcholinesterase and digestive gland superoxide dismutase activities) as well as digestive gland transcriptome were evaluated. A two-way ANOVA revealed significant effects of both “IBU concentration” and “exposure duration” on biomarker responses. Overall, the enzyme activities were generally lower in IBU-exposed clams than in controls. Although limited knowledge of the mollusc transcriptome makes it difficult to interpret the effects of IBU on clams, the gene transcription analysis using DNA microarrays enabled the identification of the putative molecular mode of action of the IBU. The functional analysis of differentially transcribed genes suggests that IBU can interfere with various signalling pathways in clams, such as arachidonic acid metabolism, apoptosis, peroxisomal proliferator-activated receptors, and nuclear factor-kappa B. In addition, several genes involved in the metabolism of xenobiotics (e.g., glutathione S-transferase, sulfotransferase, cytochrome P450) were also found to be significantly affected by IBU exposure. In summary, the integrated approach of gene transcription analysis and biomarker responses facilitated the elucidation of the putative mechanisms of action of IBU in non-target species.

Molecular biomarkers in idiopathic pulmonary fibrosis

Science.gov (United States)

Ley, Brett; Brown, Kevin K.

2014-01-01

Molecular biomarkers are highly desired in idiopathic pulmonary fibrosis (IPF), where they hold the potential to elucidate underlying disease mechanisms, accelerated drug development, and advance clinical management. Currently, there are no molecular biomarkers in widespread clinical use for IPF, and the search for potential markers remains in its infancy. Proposed core mechanisms in the pathogenesis of IPF for which candidate markers have been offered include alveolar epithelial cell dysfunction, immune dysregulation, and fibrogenesis. Useful markers reflect important pathological pathways, are practically and accurately measured, have undergone extensive validation, and are an improvement upon the current approach for their intended use. The successful development of useful molecular biomarkers is a central challenge for the future of translational research in IPF and will require collaborative efforts among those parties invested in advancing the care of patients with IPF. PMID:25260757

Biomarkers in adult posthemorrhagic hydrocephalus.

Science.gov (United States)

Hua, Cong; Zhao, Gang

2017-08-01

Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.

Downward flux of particulate fatty acids in the Central Arabian Sea

Digital Repository Service at National Institute of Oceanography (India)

Reemtsma, T.; Haake, B.; Ittekkot, V.; Nair, R.R.; Brockmann, U.H.

of their enzy- matic apparatus and their physiological needs, fatty acids have been included in the search for biomarkers, either by direct analysis of geological samples (Leo and Parker, 1966; Cooper and Blumer, 1968; Volkman and Johns, 1977) and marine... of fatty acids caused by drying at 40 °C and storage, we analysed two sediment-trap samples from another sam- pling location, which were treated in two ways: (1) dried and stored as de- scribed above or (2) immediately frozen after the addition of 10 ml...

Characterization of a genotoxicity biomarker in three-spined stickleback (Gasterosteus aculeatus L.): Biotic variability and integration in a battery of biomarkers for environmental monitoring.

Science.gov (United States)

Santos, Raphael; Joyeux, Aude; Palluel, Olivier; Palos-Ladeiro, Mélissa; Besnard, Aurélien; Blanchard, Christophe; Porcher, Jean Marc; Bony, Sylvie; Devaux, Alain; Sanchez, Wilfried

2016-04-01

As a large array of hazardous substances exhibiting genotoxicity are discharged into surface water, this work aimed at assessing the relevance of adding a genotoxicity biomarker in a battery of biomarkers recently developed in the model fish three-spined stickleback (Gasterosteus aculeatus). First the confounding influence of gender, body length, and season (used as a proxy of age and of the fish reproductive status, respectively) on the level of primary DNA damage in erythrocytes was investigated in wild sticklebacks. Then, the genotoxity biomarker was included in a large battery of biomarkers assessing xenobiotic biotransformation, oxidative stress and neurotoxicity, and implemented in five sites. Gender, age and reproductive status did not influence DNA damage level in fish from the reference site. A significant relationship between the level of primary DNA damage and fish length (as a proxy of age also correlated to the season) was highlighted in the contaminated site. Among all biomarkers investigated in the field, the level of DNA damage was one of the four most discriminating biomarkers with EROD, catalase activity and the level of lipid peroxidation representing together 75.40% of the discriminating power in sampled fish. The level of DNA damage was correlated to the EROD activity and to the level of peroxidation, which mainly discriminated fish from sites under urban pressure. Finally, Integrated Biomarker Response indexes (IBRv2), which were calculated with the whole biomarker response dataset exhibited higher values in the Reveillon (9.62), the Scarpe and Rhonelle contaminated sites (5.11 and 4.90) compared with the two reference sites (2.38 and 2.55). The present work highlights that integration of a genotoxicity biomarker in a multiparametric approach is relevant to assess ecotoxicological risk in freshwater aquatic organisms. © 2014 Wiley Periodicals, Inc.

Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans.

Science.gov (United States)

Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla; Lee, Tammy C; Morgan, Timothy M; Nicklas, Barbara J; Mathias, Rasika A; Chilton, Floyd H

2016-01-28

Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti.

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Zhou, Haonan; Zhang, Pengjie; Hou, Zhiguo; Xie, Jiabin; Wang, Yuming; Yang, Bin; Xu, Yanyan; Li, Yubo

2016-11-25

Radix Aconiti , a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

Bio-markers and the search for extinct life on Mars

Science.gov (United States)

Schwartz, D. E.; Mancinelli, R. L.

1989-01-01

In order to predict what biomarkers could be used on Mars, several biomarkers, or key signatures, of extinct life on earth are identified. Some of these biomarkers which may be applicable to Mars include reduced carbon and nitrogen compounds, CO3(2-), SO4(2-), NO3(-), Mg, Mn, Fe, and the isotopic ratios of C, N, and S. It is suggested that a fully equipped Mars rover might be able to perform analyses to measure most of these biomarkers while on the Martian surface.

Risk Factors and Biomarkers of Age-Related Macular Degeneration

Science.gov (United States)

Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

2016-01-01

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

Metabolic profiling of potential lung cancer biomarkers using bronchoalveolar lavage fluid and the integrated direct infusion/ gas chromatography mass spectrometry platform.

Science.gov (United States)

Callejón-Leblic, Belén; García-Barrera, Tamara; Grávalos-Guzmán, Jesús; Pereira-Vega, Antonio; Gómez-Ariza, José Luis

2016-08-11

Lung cancer is one of the ten most common causes of death worldwide, so that the search for early diagnosis biomarkers is a very challenging task. Bronchoalveolar lavage fluid (BALF) provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Therefore, this fluid has been explored looking for new contributions in lung cancer metabolism. In this way, two complementary metabolomics techniques based on direct infusion high resolution mass spectrometry (DI-ESI-QTOF-MS) and gas chromatography mass spectrometry (GC-MS) have been applied to compare statistically differences between lung cancer (LC) and control (C) BALF samples, using partial least square discriminant analysis (PLS-DA) in order to find and identify potential biomarkers of the disease. A total of 42 altered metabolites were found in BALF from LC. The metabolic pathway analysis showed that glutamate and glutamine metabolism pathway was mainly altered by this disease. In addition, we assessed the biomarker specificity and sensitivity according to the area under the receiver operator characteristic (ROC) curves, indicating that glycerol and phosphoric acid were potential sensitive and specific biomarkers for lung cancer diagnosis and prognosis. The search for early diagnosis of lung cancer is a very challenging task because of the high mortality associated to this disease and its critical linkage to the initiation of treatment. Bronchoalveolar lavage fluid provides information on cellular and biochemical epithelial surface of the lower respiratory tract constituents and no previous metabolomic studies have been performed with BALF samples from patients with lung cancer. Since BALF is in close interaction with lung tissue it is a more representative sample of lung status than other peripheral biofluids as blood or urine studied in previous works

High Serum Essential Amino Acids as a Predictor of Skeletal Muscle Depletion in Patients With Cachexia and Advanced Gastrointestinal Cancers.

Science.gov (United States)

Kitagawa, Moeko; Haji, Seiji; Amagai, Teruyoshi

2017-10-01

In recent years, the number of patients with cancer has increased. These patients are prone to sarcopenia as a result of the decrease in muscle mass and muscle weakness that occur in cancer cachexia. Amino Index Cancer Screening is carried out to evaluate cancer cachexia risk by examining amino acid concentration and analyzing amino acid balance. We conducted a retrospective chart review of consecutive patients with unresectable advanced gastrointestinal cancer (stage IV) receiving chemotherapy treatment (December 2012-September 2015) in an outpatient or in-hospital setting at our institution (N = 46). Data included characteristics, psoas muscle area per computed tomography, and biochemical blood test and serum amino acid profiles. Method 1: Comparison of biomarkers between 2 groups: psoas muscle index change rate (ΔPMI) decrease vs increase. Method 2.1: Correlation between ΔPMI and biomarkers. Method 2.2: Multiple regression of ΔPMI and biomarkers. EAA/TAA ratio (essential amino acids/total amino acids) in the decrease group was significantly higher than that in the increase group. Among all parameters, serum C-reactive protein (CRP), leucine, and isoleucine were negatively related to ΔPMI (correlation coefficients = -0.604, -0.540, -0.518; P = .004, .011, .016, respectively). On multiple regression analysis, serum CRP value was strongly related to ΔPMI ( r 2 = 0.452, β = -0.672, P = .001). Higher serum EAA/TAA ratio and CRP were associated with depletion in psoas muscle area, which led to a diagnosis of sarcopenia, in patients with advanced gastrointestinal cancers. These parameters at baseline could be predictors of cancer cachexia.

Plasma phospholipid fatty acid profiles in Korean adults with and without acute coronary syndrome

Science.gov (United States)

Background and Objectives: Acute coronary syndrome (ACS), a clinical manifestation of coronary artery disease presenting as unstable angina and/or myocardial infarction, is the third-leading cause of death in South Korea. Plasma phospholipid (PL) fatty acid profiles are considered objective biomarke...

Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females.

Science.gov (United States)

Abdullah, Abdul Ridha; Hasan, Haydar A; Raigangar, Veena L

2009-02-01

Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively). Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

Simultaneous detection of diagnostic biomarkers of alkaptonuria, ornithine carbamoyltransferase deficiency, and neuroblastoma disease by high-performance liquid chromatography/tandem mass spectrometry.

Science.gov (United States)

Hsu, Wei-Yi; Chen, Ching-Ming; Tsai, Fuu-Jen; Lai, Chien-Chen

2013-05-01

Urinary homovanillic acid (HVA)/vanillylmandelic acid (VMA), orotic acid (OA), and homogentisic acid (HGA) are diagnostic biomarkers of neuroblastoma, ornithine carbamoyl transferase deficiency (OCTD), and alkaptonuria (AKU), respectively. In this study, a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous quantification of HVA, VMA, OA, and HGA in urine. After sample preparation, which involved only the dilution procedure, samples were quantified by LC-MS/MS. Full-scan MS/MS mode enabled the urinary markers to be quantified with a high degree of specificity and sensitivity. Rather than using a separate enzymatic method to normalize the concentration of creatinine in urine, we quantified the level of creatinine in urine in one LC-MS run. The limits of detection were 10 μg/l for HGA, 25 μg/l for HVA/VMA, and 50 μg/l for OA with a single-to-noise ratio of 3; the limits of quantification were 50 μg/l for HVA and HGA, 100 μg/l for VMA, and 250 μg/l for OA. The linear dynamic range for quantification of the analytes covered 2 to 3 orders of magnitude, depending on the analyte. The relative standard deviation of the developed LC-MS/MS method was less than 4% for the intra-day validation and 10% for the inter-day validation. The results show that our LC-MS/MS technique is a highly sensitive and rapid method for screening for biomarkers that are diagnostic of three metabolic diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Biomarkers in scleroderma: Current status

Directory of Open Access Journals (Sweden)

Latika Gupta

2017-01-01

Full Text Available Scleroderma is an autoimmune disease characterized by indolent obliterative vasculopathy and widespread fibrosis. The two main morphological manifestations of the disease overlap and may make it difficult to separate activity from damage. Many patients, especially those with the limited subset of the disease, have an indolent course without clear-cut inflammatory manifestations. There is a felt need for validated biomarkers, which can differentiate activity from damage, and yet be sensitive to change with therapy. Multiplex arrays of biomarkers have ushered an era of targeted or personalized medicine based on phenotypic characteristics in an individual.

Multiomics Data Triangulation for Asthma Candidate Biomarkers and Precision Medicine.

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Pecak, Matija; Korošec, Peter; Kunej, Tanja

2018-06-01

Asthma is a common complex disorder and has been subject to intensive omics research for disease susceptibility and therapeutic innovation. Candidate biomarkers of asthma and its precision treatment demand that they stand the test of multiomics data triangulation before they can be prioritized for clinical applications. We classified the biomarkers of asthma after a search of the literature and based on whether or not a given biomarker candidate is reported in multiple omics platforms and methodologies, using PubMed and Web of Science, we identified omics studies of asthma conducted on diverse platforms using keywords, such as asthma, genomics, metabolomics, and epigenomics. We extracted data about asthma candidate biomarkers from 73 articles and developed a catalog of 190 potential asthma biomarkers (167 human, 23 animal data), comprising DNA loci, transcripts, proteins, metabolites, epimutations, and noncoding RNAs. The data were sorted according to 13 omics types: genomics, epigenomics, transcriptomics, proteomics, interactomics, metabolomics, ncRNAomics, glycomics, lipidomics, environmental omics, pharmacogenomics, phenomics, and integrative omics. Importantly, we found that 10 candidate biomarkers were apparent in at least two or more omics levels, thus promising potential for further biomarker research and development and precision medicine applications. This multiomics catalog reported herein for the first time contributes to future decision-making on prioritization of biomarkers and validation efforts for precision medicine in asthma. The findings may also facilitate meta-analyses and integrative omics studies in the future.

Incorporating biomarkers in ecological risk assessment of chemical contaminants of soils

Directory of Open Access Journals (Sweden)

A. J. Reinecke

2007-09-01

Full Text Available Soil is an important but complex natural resource which is increasingly used as sink for chemicals. The monitoring of soil quality and the assessment of risks posed by contaminants have become crucial. This study deals with the potential use of biomarkers in the monitoring of soils and the assessment of risk resulting from contamination. Apart from an overview of the existing literature on biomarkers, the results of various of our field experiments in South African soils are discussed. Biomarkers may have potential in the assessment of risk because they can indicate at an early stage that exposure has taken place and that a toxic response has been initiated. It is therefore expected that early biomarkers will play an increasing role as diagnostic tools for determining exposure to chemicals and the resulting effects. They may have predictive value that can assist in the prevention or minimising of risks. The aim of this study was to investigate the possibilities of using our results on biomarker responses of soil dwelling organisms to predict changes at higher organisational levels (which may have ecological implications. Our recent experimental results on the evaluation of various biomarkers in both the laboratory and the field are interpreted and placed in perspective within the broader framework of response biology. The aim was further to contribute to the development and application of biomarkers in regulatory risk assessment schemes of soils. This critical review of our own and recent literature on biomarkers in ecotoxicology leads to the conclusion that biomarkers can, under certain conditions, be useful tools in risk assessment. Clear relationships between contamination loads in soil organisms and certain biomarker responses were determined in woodlice, earthworms and terrestrial snails. Clear correlations were also established in field experiments between biomarker responses and changes at the population level. This indicated that, in

A scheme for a flexible classification of dietary and health biomarkers

DEFF Research Database (Denmark)

Gao, Qian; Pratico, Giulia; Scalbert, Augustin

2017-01-01

to have a solid scheme for biomarker classification that will provide a well-defined ontology for the field. In this manuscript, we provide an improved scheme for biomarker classification based on their intended use rather than the technology or outcomes (six subclasses are suggested: food compound intake...... in the scientific literature. However, the existing concepts for classification of biomarkers in the dietary and health area may be ambiguous, leading to uncertainty about their application. In order to better understand the potential of biomarkers and to communicate their use and application, it is imperative...... with previous biomarker classification for this field of research....